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Combine Notes Microbiology
And Immunology
welcome
Course outline
Microbiology
• Historical background
• Classification & properties of microorganisms
• Clinical importance of micro-organisms
• Sources of micro-organisms
• Modes of transmission of infections
• Concept of infection (definition of terms
related to infection; stages of development of
infection; common nosocomial infections)
Immunology
Types of immunity;
 humoral
cell mediated
Passive
active
herd immunity
• Antigen-antibody reaction
• Types of antibodies
• Modes of action of antibodies
• Complement system of immunity
MICROBIOLOGY
• Microbiology is the study of organisms too
small to be seen by the naked eye
• Microbiology is the branch of science that
deals with the study of micro organisms
• these organisms include viruses, bacteria,
fungi and protozoa
• Medical microbiology is the study of causative
agents of infectious diseases of humans and
their reaction to such infections
• it deals with etiology, pathogenesis, laboratory
diagnosis, specific treatment and control of
infection (immunization)
• It deals with microbes-the causative agent of
infectious diseases
Historical background
Microbiology had its beginning in the ancient times
with an awareness in sanitation ( Hippocrates)
Historical eras of microbiology
1. Biblical times- 1500 BC
Levitical law with strict laws concerning
sanitation, an diseases like leprosy
2. Ancient times of the Greeks and Romans – 146-
476 AD
They insisted on sewage systems, clean water,
regular bathing, latrines and ventiltion
Dark ages ( 400 AD- 1100 AD)
This was a period of loss of knowledge and practice
was based on superstition and forces
4. Renaissance/ Enlightment age-1200 AD-1700AD
There was a hunger for knowledge and reasons and
facts became the basis for actions and
procedures
5. Golden Age- 1800 AD
This was the advent of microbiology and
microscopy
Principal Contributors to Microbiology
1674
Anton Van Leeuwenhoek
• Dutch biologist – was the first man to observe bacteria
and other microorganisms using a single lens
microscope of his own design and drew them and
documented them, forming the basis of microbiology
1796
Edward Jenner
• using ancient Chinese technique for small pox
vaccination developed a method of using cowpox to
immunize a child against small pox. The same
principles are used for developing vaccines today
1840
Friedrich Henle
• proposed a criteria for proving that
microorganisms caused human diseases (germ
theory of disease)
1857
Louis Pasteur
• Father of modern medicine
• He was a French chemist who disapproved the
theory of spontaneous generation
• He proved that lactic fermentation was due
to living organisms and based on
experiments proved that fermentation of
wine was caused by bacteria
• designed vaccines against anthrax, cholera
and rabies as well as pasteurization for food
preservation.
1867
• Joseph Lister; father of antiseptic surgery; first
to sterilize instruments and reduce infections
1884
• Hans Christian Gram; developed a method of
staining bacteria to make them visible under a
microscope
1842-1910
Robert Koch
• German physician
• Studied the disease anthrax
• Developed a method to identify the etiologic
agent
• First to identify Bacillus anthracis as etiologic
agent to anthrax (1877)
• Developed a set of postulates
The germ theory of disease
• States that micro-organisms known as
pathogens or “germs” can lead to disease.
These small organisms, too small to see
without magnification, invade humans, other
animals and other living hosts.
• Their growth and reproduction within their
hosts can cause disease.
Scope and Importance of microbiology
• Production of antibiotics e.g. penicillin from
penicillium
• Production of enzymes, vaccines,
biosurfactants, alcoholic and other
pharmaceutical products
• Diagnosis of disease and treatment e.g. ELISA,
widal test
• Treatment of industrial waste material
• Plant growth promotion
• Sterile product preparation and
Sterilization(process of killing microorganisms)
• Identification of microorganisms e.g.
morphological, cultural or microscopic study
• Testing of pharmaceutical products and raw
materials
Importance of microbiology in nursing
• Helps the nurse to know pathogens, their
sources and composition
• Helps to know how these micro organisms are
transmitted and how they spread diseases
• It is a step in prevention and cure of many
diseases
• Helps the nurse to take universal precautions
when in the hospital environment
• It an important aspect in infection control
• Forms a rich source in health education,
immunization and surveillance
Definitions of term
• Ecology – relations of microorganisms to one
another and to their physical surroundings
• Saprophytes – a term used for plants, fungi or
bacteria which obtain nutrients from dead
organic matter
• Symbiosis – the relationship between 2
different kinds of organisms living in close
physical association to the advantage of both
sometimes referred to as mutualism e.g. gut
protozoa in herbivores – receive nutrients, help
animals digest, nitrogen fixing bacteria that live in
the roots of legumes, lactobacillus in stomach
• Commensal - an organism living with, on or in
another without causing injury. Refers to a
relationship in which one organism derives food
and other benefits from another without hurting
or helping it e.g normal flora in the mouth
Parasite
• an organism that obtains shelter and
nourishment on another organisms (host). It is a
non mutual relationship where one species
benefits at the expense of the other
• They are capable of causing harm and disease to
their host and are generally much smaller than
their host e.g Macroparasites -ticks, lice,
tapeworm or microparasites- bacteria, viruses,
fungi
• Pathogen – microorganism capable of causing
disease
• Virulence – the degree of pathogenicity of an
organism or measure of the ability of an
organism to cause disease
• Pathogens/causative agent: Microbes that are
capable of causing disease are called
pathogenic.
• Infectious disease process: The interaction be
tween the pathogen microorganism, the envir
onment and the host
• An infection: when pathogen invades the bod
y and the conditions are favorable for it to mul
tiply and cause injurious effects or disease.
• Vaccine: an antigenic substance prepared fro
m the causative agent of a disease or a synthe
tic substitute, used to provide immunity again
st one or several diseases
• Incubation period – the time between exposu
re to a pathogenic organism and when first sy
mptoms apparent
Modes of transmission of
microorganisms
Direct transmission:
• Direct contact
• Droplet infection
• Innoculation into skin or mucosa
• Transplacental (vertical
Indirect transmission:
• Vehicle borne (water/ blood)
• Vector borne
• Air borne
• Fomite borne
Nosocomial infections
• Nosocomial infections are also referred to as
hospital acquired infections
• Infections are considered nosocomial if they
first appear 48hours or more after hospital
admission or within 30 days after discharge
Causes of rise in nosocomial infections
• Crowded hospital conditions
• New microorganisms
• Increasing number of people with
compromised immune system
• Increasing bacterial resistance
• Contaminated hospital environment
• Contaminated instruments (invasive devices)
• Medical personel; colonized infected transient
carriers
• Patient flora: cutaneous, gastrointestinal,
respiratory, genitourinary
Common sites of infection
• Surgical wounds
• Urinary tract
• Skin
• Respiratory tract
Impact of nosocomial infections
• Prolonged hospital stay
• Additional morbidity
• Increased mortality
• Long-term physical and psychological
consequences
• Increased cost of care
SOURCES AND SPREAD OF INFECTION
Sources of infection
Environmental sou
rces
Person- to-person Medical or surgical proce
dures
Self-infection
Inanimate/nonlivin
g objects
Water, food, soil,
etc.
Animals (bites and
scratches;
zoonoses)
Arthropod vectors
Airborne infection
Direct contact
(touching,
kissing, etc.)
Maternal
transmission
(intrauterine,
transplacental)
Sexual transmission
Instrumentation, operation
s
Transfusion (blood and
blood products)
Transplants (tissues,
organs)
Endogenous s
ources (n
ormal flor
a)
Shared
needles
Needlestick
injuries
Infected person or he
althy carriers
Basic classifications of microorganisms
–Eukaryotic microorganisms – organisms
whose cells contain a nucleus and other
structures enclosed within membranes e.g.
fungi, protozoa, slime moulds, algae
–Prokaryotic microorganisms – is a single-
celled organism that lacks a membrane-
bound nucleus , mitochondria, or any other
membrane-bound organelle e.g. bacteria
Differences between prokaryote and eukaryote cells
Prokaryotic cells Eukaryote cells
1. Small cell (<5µm) Larger (>10µm)
2. Always unicellular Often multicellular
3. No nucleus or any membrane
bound organelles
Always have nucleus and
membranes bound organelles
4. DNA circular, without proteins DNA is linear and associated
with proteins to form chromatin
5. Cell division is by binary fission Cell division is by meiosis and
mitosis
6
.
Ribosmes are small Ribosomes are large
7. No cytoskeleton Always have
cytoskeleton
8. Motility by rigid
rotating flagellum
made from flagellin
Motility by flexible
waving cilia or flagella
made from tubulins
9. Reproduction is
always asexual
Reproduction is
sexual or asexual
Factors promoting Growth and
Development of Micro-organisms
1. Temperature:
• Determines the rate of growth, multiplication,
survival and death of all living organisms.
• High temperatures damage microbes by
denaturing enzymes, transport carriers, and
other proteins; Microbial membranes are
disrupted by temperature extremes; At very
low temperatures, membranes also solidify
and enzymes also do not function properly
• Can be divided into:
• Psychrophilles – prefer temperature of
0-5 degrees
• Mesophilles - prefer temperature of 20-
45 degrees
• Thermophilles – prefer temperature of
above 55 degrees
2. PH Levels:
• Refers to negative logarithm of hydrogen ion
concentration
• Microbial growth is strongly affected by the PH of
the medium
• Drastic variations in cytoplasmic PH disrupt the
plasma membrane or inhibit the activity of
enzymes and membrane transport proteins
• Acidophiles, alkalophiles, neutrophiles;
Most prefer neutral PH
3. Moisture – free flow of water is important to
microorganisms for their cells to exchange nutrients
and for metabolic processes. All microorganisms
require water, some less. The more moisture, the
more microorganisms will be found
4. Oxygen and nitrogen–Many microorganism
require an oxygen rich environment (aerobic) but
others flourish in low oxygen surroundings
(anaerobic) or some can survive in either
Classification of micro-organism
• Bacteria
• Viruses
• Fungi
• Parasites
BACTERIA
• Are unicellular prokaryocytes, have neither a
well defined nucleus nor a nucleus membrane
• It consists of a unique cell wall, cytoplasmic
membrane enclosing the cytoplasm,
mesosomes, a nucleus apparatus, ribosomes
and cytoplasmic granules. Some have flagella,
pili and can produce spores
• They have a large surface area to volume ratio
and can gain food rapidly from their
environment by diffusion and active transport
• Unlike most other organisms, bacteria have
few morphological differences that can be
used to classify them
• Bacteria do not vary in size and shape to the
extent that other types of organisms do
• They reproduce by binary fission
(asexually) and branching (budding)
• Classically, bacteria have been grouped and
based on structure, physiology, molecular
composition and reaction to specific stains
(gram stain)
• The three common types of bacterial
morphology are
cocci/ coccus
bacilli/ bacillus
spirillum/spirochetes
• Bacteria are classified according to their cell
wall characteristics as either gram positive or
gram negative.
• Differences in the cell wall account for the
differences in their functional properties as
well as their susceptibility to antimicrobial
agents.
• In gram positive bacteria the cell wall called
peptidoglycan forms a thick layer to the cell
membrane and may contain other
macromolecules.
• In gram negative bacteria the peptidoglycan is
thin and is overlaid by an outer membrane,
anchored to lipoprotein molecules.
• Many bacteria species are less demanding
nutritionally and may require a single organic
compound to meet all of their biosynthetic
needs
• The cell must encounter acceptable conditions
of temperature, oxygen, PH, moisture and
ionic strength
• Some bacteria are obligate aerobes i.e.
Require oxygen while others are anaerobes
• Facultative bacteria is one that can
survive in both aerobic and anaerobic
conditions.
• Bacteria obtain nutrients mainly by taking
up small molecules across the cell wall.
• In human beings the optimum PH for
bacterial growth is between 7.2- 7.6.
Gram staining (or Gram's
method)
is a method of differentiating bacterial
species into two large groups (Gram-
positive and Gram-negative).
It is based on the chemical and physical
properties of their cell walls. Primarily, it
detects peptidoglycan, which is present in a
thick layer in Gram positive bacteria. A
Gram +ve results in a purple/blue color
while a Gram -ve results in a pink/red color.
• Gram stain is almost always the first step in
the identification of a bacterial organism,
and is the default stain performed by
laboratories over a sample when no specific
culture is referred.
While Gram staining is a valuable diagnostic tool
in both clinical and research settings, not all
bacteria can be definitively classified by this
technique, thus forming Gram-variable and
Gram-indeterminate groups as well.
The word Gram is always spelled with a capital,
referring to Hans Christian Gram, the inventor
of Gram staining.
Gram-positive bacteria have a thick mesh-like
cell wall made of peptidoglycan (50-90%
of cell envelope), which are stained purple
by crystal violet.
Gram-negative bacteria, on the other hand,
have a thinner layer (10% of cell envelope),
which are stained pink by the counter-stain.
There are four basic steps of the Gram stain:
(i) Applying a primary stain (crystal violet) to a
heat-fixed smear of a bacterial culture. Heat fixing
kills some bacteria but is mostly used to affix the
bacteria to the slide so that they don't rinse out
during the staining procedure.
(ii) The addition of a mordant, which binds to
crystal violet and traps it in the cell (Gram's
iodine)
iii) Rapid decolorization with alcohol or
acetone, and
(iv) Counterstaining with safranin. Carbol
fuchsin is sometimes substituted for
safranin since it will more intensely stain
anaerobic bacteria but it is much less
commonly employed as a counterstain.
Bacterial cell division
1. Bacteria reproduce asexually via binary
fusion
• Replication of bacterial chromosome triggers
initiation of cell division
• Cell wall extends, septum is formed
• Septum grows and cleaves the daughter cell.
• Incomplete cleavage of the septum can cause
bacteria to remain linked forming chains –
streptococcus or clusters – Staphylococcus
2. spore formation
• Some gram +ve bacteria species form spores
e.g Bacillus sp. and Clostridia Sp. Esp in harsh
environment such as lack of nutrients
• Gram –ve bacteria do not form spores
• The spore has a copy of the chromosome,
ribosomes and essential proteins, outer
membrane, 2 peptidoglycan layers and an
outer keratin like protein layer.
• The spore protects bacterial DNA from
desiccation, intense heat, radiation and attack
by enzymes and chemicals
• Are so resistant that they can remain viable
for centuries
• They are difficult to decontaminate with
standard disinfectants.
Bacterial metabolism
• In general, bacteria require a source of
carbon, nitrogen, an energy source, water and
various ions for growth. Pathogenic bacteria
derive energy from metabolizing sugars, fats
and proteins.
• Not all bacteria require oxygen for growth:
–Obligate anaerobes – cannot grow in the
presence of oxygen e.g clostridium
perfringes
–Obligate aerobes – require oxygen for
growth e.g Mycobacterium tuberculosis
–Facultative anaerobes – grow in either the
presence or absence of oxygen
Bacterial growth
• For bacterial growth to occur, there must be
sufficient metabolites to support synthesis of
bacterial components.
– When bacteria are added to a medium, they
require time to adapt to the new environment
before they start dividing. This is the lag phase
– They then grow and divide during the log or
exponential phase
– Eventually the culture runs out of metabolites
and toxins build up . the bacteria stop growing
and enter the stationary phase.
GRAM –ve GRAM +ve
Borellia – spirochete Streptomyces
Bordatella – Rod Streptococcus – cocci in chains
Campylobacter – curved rod Staphylococcus – cocci in clusters
Treponema - spirochete Nocardia
Vibrio – rod Listeria - rods
Yersinia – rod Lactobacillus
Chlamydia Gardnerella - rods
Enterobacter Enterococcus
Escherichia – Rods Corynebacteria
Helicobacter – curved Rods Clostridium- spore forming
Hemophillus - Rods Bacillus – rods, some spore forming
Klebsiella – rods Actinomyces
Legionella – rods
Leptospira - spirochete EXCEPTIONS
Nesseria – diplococcus Mycoplasma – No cell wall
Pseudomonas - rod Mycobacteria – Acid fast bacilli
Ricketssia
Salmonella – rod
Shigella – rod
FUNGI
Study of fungi is referred to as mycology
– Fungi cause diseases in humans
– They also contribute to food spoilage, are a
major cause of plant disease and destroy
timber, textiles and several synthetic materials
– They play a role in the decay of plant and
animal remains in the soil
– Fungi are also beneficial to humans in that
they are used in production of antibiotics,
steroids, products of fermentation – alcohol,
cheese, wine, bread making
• They occupy many niches in the environment
• They are free living and abundant in nature,
only few exist as normal flora in humans
• Fewer of them are associated with human
disease
• Fungi do not need to colonise or infect tissues
of animals or man to perpetuate or preserve
the species ( with the exception of candidiasis
and tinea versicolor)
Structure
• Have a typical eukaryotic cell
• They have a cell wall made of chitin
• Some fungi have a polysaccharide capsule
around the cell wall to isolate it from the
environment. This helps in virulence if the fungi
are pathogenic
• Most fungi respire aerobically, others are strict
anaerobes and others are facultative anaerobes
• They have special staining to identify them
• fungi are heterotrophic ( “other feeding,”
must feed on preformed organic material), not
autotrophic ( “self feeding,” make their own
food by photosynthesis).
• - Unlike animals (also heterotrophic), which
ingest then digest, fungi digest then ingest:
they produce exoenzymes to accomplish this
• Most fungi store their food as glycogen (like
animals). Plants store food as starch.
• Fungal cell membranes have a unique sterol,
ergosterol, which replaces cholesterol found
in mammalian cell membranes
• The body of fungi is termed thallus
(nonreproductive)
–The thalli of yeast are small, globular and
are single celled
–The thalli of mold are composed of long,
branched tubular filaments called hyphae.
classification
• Fungi can be divided into 2 basic
morphological forms:
–Yeast – unicellular, reproduce asexually by
budding or fission
–Molds (Hyphae) – branching, thread like,
tubular filaments.they elongate at their tips
by a process called apical extension. A mass
of hyphae forms a mycelium ( commonly
known as mold)
• The morphology of fungi is not fixed. Some
can exist in hyphae or yeast form (dimorphic)
depending on the environment (i.e in soil,
decaying tissue or in host tissue)
• Most pathogenic fungi are dimorphic fungi
–At 37° C; yeast-like
–At 25° C: mold-like
–Can also occur with changes in CO2
hyphae
Most reproduce by budding
examples
• Candida albicans – part of the normal flora of
mouth, GIT and vaginal wall
• Malassezia furfur – causes skin infection
• HIstoplasma capsulatum
• Blastomyces dermatitidis
• Coccidiodes immitis
• Trichophyton and Microsporum sp. – cause ring
worm
• Cryptococcus neoformans – cryptococcal
meningitis in ISS
Human pathological fungi
• The majority of most human pathogenic fungi
appear to be soil inhabiting species where
they live as saprobes
• Given the appropriate conditions, i.e. if the
person is not healthy, an open wound is
present, direct injection of fungus into the
system, a particular life-style, AIDS, etc., they
will aggressively attack people
Superficial infections/ cutaneous
• Are caused by fungi that attack the skin or its
appendages (nail, feathers and hair).
• Some examples of these infection include
ringworms, jock-itch(tinea cruris) and athlete's
foot.
• These fungi are known as dermatophytes
Ringworm and Related
Dermatophytes
• Ringworm usually occurs on the exposed parts
of the body, forming circular growths that may
appear darker or lighter than the normal skin
color, with symptoms that include skin lesion,
rash and itching of the infected area
• Caused by Trichophyton and Microsporum
• They include;
– Tinea capitis: Ringworm of the scalp, eyebrow and
lashes.
– Tinea corporis: Ringworm of the body.
– Tinea cruris: Ringworm of the groin, perineum and
perianal region. Infections are commonly referred to as
"jock itch".
– Tinea unguium: Ringworm of the nail.
– Tinea barbae: Ringworm of the beard.
– Tinea pedis: Ringworm of the feet. Infections are
commonly referred to as athlete's foot.
– Tinea manuum: Ringworm of the hand.
Systemic or Deep-Seated Mycoses
Coccidioides immitis
• The cause of Coccidioidomycosis (Valley Fever)
–Coccidioides immitis is contracted by
inhalation of spores and primarily causes a
respiratory disease in animals and people,
but from the lungs it may spread
throughout the body by way of the
bloodstream
• Histoplasma capsulatum and Histoplasmosis
–Histoplasmosis occurs in people and dogs,
rarely has it occurred in other domestic or
wild animals.
–Infection occurs through inhalation of
spores from this fungus.
• Blastomyces and Blastomycosis
– There are two species of this genus,
Blastomyces dermatitidis and B. brasiliensis
Infection apparently comes from spores or
mycelium in the soil and any part of the body
may be invaded.
– Infections usually are first detected as skin
lesions; the lesions may remain localized or
may gradually enlarge. In some case the fungus
can spread throughout the whole body,
resulting in extensive ulceration.
Intermediate Infections
(subcutaneous
• These are diseases that are intermediate
between the first two categories.
• These fungal infections may extend to a
considerable depth within the tissue, but
unlike the systemic diseases will not be
distributed to the rest of the body.
• One of the most common intermediate
infection is Candida albicans.
Candida albicans and Candidiasis
– Candida albicans is a dimorphic fungus. That is,
it grows as both mycelium and yeasts..
– This fungus normally occurs in the mouth,
digestive tract, and vagina of perfectly healthy
people, but under some circumstances, and for
reasons unknown, it may cause severe and
even fatal infections, with lesions and
eruptions of the skin, nails, mouth, bronchial
tubes and lungs.
– Oral infections known as thrush is relatively
common..
Aspergillus fumigatus and
Aspergillosis
– Aspergillus fumigatus sometimes parasitizes
animals, especially birds, infecting mainly lungs
and causing heavy mortality in birds.
– In people, the disease can lead to a chronic
lung infection which is apparently very
contagious. The fungus is thought to cause
death, but that is not certain. In patients that
have died and A. fumigatus has been isolated,
many have also had underlying disease that
possibly lowered their resistance to the fungus.
PARASITES
Types of parasites according to living
environment:
• Ectoparasite: Living on the surface of other
organisms lice, ticks, mites, etc.
• Endoparasites: Live inside the body of other
organism, e.g. Entamoeba histolytica, Ascaris
lumbricoides, etc.
• Obligate parasites: spend some part of their life
cycle in or on host, e.g. plasmodium.
• Facultative parasites: may be free living but
can obtain the nutrition from hosts too.
• Accidental parasites: when parasite attacks
unnatural host.
• Aberrant parasite: when the parasite comes
to a site, during migration where it cannot live
or develop further
Types of host
• Definitive host: when it harbors parasite in
adult form or where parasite utilizes sexual
method of reproduction).
• Intermediate host: harbor’s larval stages of
parasite).
• Paratenic host: when host harbors parasite
exhibiting no development but this parasite
remains viable).
• Reservoir host: which make parasites available
for transmission to other hosts.
• Natural host: which is naturally infected with
certain species of parasite.
• Accidental host: one who is not usually
infected with parasite.
The Effect of Parasites on their Host
1. Mechanical Injury:
–Pressure created in tissues as it grows
larger, e.g. hydatid cyst
–Blockage of ducts such as
• Blood vessels producing infarction, e.g.
strongyloides
• Lymphatic vessels to produce edema and
elephantiasis, e.g. filariasis
• The intestinal tract to produce
obstruction, perforation and necrosis,
e.g. Ascaris lumbricoides
–Destruction of architecture of the human
red blood cells by Plasmodium falciparum.
2. Producing toxic substances
–Plasmodium falciparum, produce toxic
substances may cause rigors and other
symptoms characteristic of clinical malaria.
–Entamoeba histolytica lesions in human gut
may be due to the production of histolytic
enzyme (tissue dissolving).
3. Deprivation of Nutrients, Fluids and Metabolites
– Diphylobothrium latum (fish tapeworm) is
known to deprive its host of vitamin B12 thus
causing megaloblastic anemia.
– Ancylostoma duodenale and some other blood
sucking arthropod parasites quickly lead to
severe iron deficiency anemia in patients
infested by large numbers of these parasites
4. Introduction of Pathogenic Microorganisms
– Bacterial infection of lesions produced initially
by a parasite may occur and in some cases may
prove lethal, e.g. tetanus is a well-known
complication of Dracunculus medinensis
infection.
– This is the result of the spores of Clostridium
tetani contaminating the ulcers of the foot and
digit, produced by Dracunculus medinensis.
Classification of parasites
1. According to their anatomical habitat in
humans, they are classified into two groups
a) ectoparasites (parasitizing the skin surface
b) Endoparasites: parasitizing the internal
tissues
2. According to their cellular structure, they are
classified into two groups:
a) Protozoa (each is unicellular
b) Metazoa (multicellular)
PROTOZOA
According to the body systems they are
classified into :
a) Hemopoietic
b) Intestinal
c) Genitourinary
d) Cutaneous
e) Others
1. Hemopoietic protozoa:
–Plasmodium species
–Leishmania species
–Trypanosoma species
–Toxoplasma species
2. Intestinal protozoa:
–Entamoeba histolytica
–Blantidium coli
–Giardia lamblia
–Cryptosporidium parvum
–Isospora belli
3. Genitourinary: Trichomonas vaginalis
Metazoa
• Classified into nematodes, helminthes
• Helminthes are further classified into:
1. Cestodes
2. Nematodes
3. Trematodes
Cestodes (tapeworms)
1. Taenia saginata and Taenia solium
2. Hymenolepis nana
3. Diphyllobothrium latum
4. Dipylidium caninum
5. Echinococcus granulosus
6. Echinococcus multolocularis
Nematodes (roundworms)
• Further classified into intestinal nematodes,
tissue nematodes and trematodes
• Ascaris lumbricoides
• Hookworms
• Enterobius vermicularis
• Trichuris trichiura
Trematodes (flukes)
• Schistosoma masoni
• Schistosoma haematobium
• Schistosoma japonicum
• Hermaphroditic flukes
Adult Schistosoma (male and female)
Fasciolopsis buski (intestinal flukes)
VIRUSES
• Viruses are the smallest microorganism –
smaller than bacteria.
• The smallest viruses are about 0.02 μm (20
nanometers), while the large viruses measure
about 0.3 μm (300 nanometers). Smallpox
viruses are among the largest viruses; polio
viruses are among the smallest.
• Viruses are noncellular genetic elements that
use a living cell for their replication and have
an extracellular state.
• Viruses are ultramicroscopic particles
containing nucleic acid surrounded by protein,
and in some cases, other components such as
a membrane like envelope.
• Viruses are obligate intracellular parasites – depend on
the host cell for replication.
• Viruses cannot make energy, proteins or replicate their
genome outside the host cell.
• The virus therefore must adapt to the biochemical
nature of the host cell to use its systems. They
therefore must be infectious to survive.
• Outside the host cell, the virus particle is also known as
a virion. The virion is metabolically inert and does not
grow or carry on respiratory or biosynthetic functions.
Classification of viruses
• Viruses can be classified according to :
– Structure – size, morphology
– Genome – mode of replication – DNA or RNA
– Disease they cause
– Means of transmission e.g air, waterborne
– Host cell – plants, animals and bacteria
• For our level, viruses will be classified according
to their genetic material or means of replication.
DNA viruses RNAViruses
Family Members Family Members
Poxviridae Smallpox,
Herpes simplex,
Varicella zoster virus
Cytomegalovirus
paramyxoviridae measles virus
mumps virus
Adenoviridae Adenovirus Orthomyxoviridae Influenza virus
Hepadnaviridae Hepatitis B
virus
Rhabdoviridae Rabies virus
Papoviridae Human
papilloma virus
Filoviridae Ebola virus
Marbug virus
Retroviridae Human
immunodeficiency
virus (HIV)
Human T cell
leukemia virus
DNA viruses RNAViruses
DNA RNA
Reoviridae Rotavirus
Picornavirida
e
Polio virus
Rhinoviruses
Togaviridae Rubella virus
Coronaviridae Corona Virus
Viral Structure and Replication
• Certain viruses contain ribonucleic acid (RNA),
while other viruses have deoxyribonucleic acid
(DNA). The nucleic acid portion of the viruses
is known as the genome.
• The nucleic acid may be single-stranded or
double-stranded; it may be linear or a closed
loop; it may be continuous or occur in
segments.
• The genome of the virus is surrounded by a
protein coat known as a capsid, which is
formed from a number of individual protein
molecules called capsomeres. Capsomeres are
arranged in a precise and highly repetitive
pattern around the nucleic acid. The
combination of genome and capsid is called
the viral nucleocapsid.
• A number of kinds of viruses
contain envelopes. An envelope is a
membrane like structure that encloses the
nucleocapsid and is obtained from a host cell
during the replication process.
• The envelope contains viral-specified proteins
that make it unique. Among the envelope
viruses are those of herpes simplex,
chickenpox, and infectious mononucleosis
Viral structure
Viral replication
• Attachment. , the virus adsorbs to a susceptible host
cell using spikes. Cell surface receptors may exist on
bacterial pili or flagella or on the host cell membrane.
• Penetration of the virus or the viral genome into the
cell. May occur by phagocytosis; or the envelope of the
virus may blend with the cell membrane
• Replication;
– The protein capsid is stripped away from the genome, and
the genome is freed in the cell cytoplasm where it either
act as a messenger RNA (in RNA viruses)or synthesize
messenger RNA from DNA (in DNA viruses)that provides
codes for synthesis of enzymes
• Viral protein synthesis – carried out on host
cell ribosomes
• Assembly - viral parts come together and
enclose viral genome in a functional package
• Release of new viral particles;
NB; The replication process in which the host
cell dies is called the lytic cycle of reproduction.
The viruses so produced are free to infect and
replicate in other host cells in the area.
Lysogeny
• Not all viruses multiply by the lytic cycle of
reproduction.
• Certain viruses remain active within their host
cells for a long period without replicating. This
cycle is called the lysogenic cycle.
• The viruses are called temperate viruses,
or proviruses, because they do not bring death to
the host cell immediately.
• The temperate virus exists in a latent form within
the host cell and is usually integrated into the
chromosome.
• An example of lysogeny occurs in HIV
infection. In this case, the human
immunodeficiency virus remains latent within
the host T-lymphocyte. An individual whose
infection is at this stage will not experience
the symptoms of AIDS until a later date
Anatomy of corona virus
IMMUNOLOGY
Introduction
• The word Immune if from latin word “immunus”
meaning to be free
• Immunity also refers to when people survive a
calamity of epidemic diseases when faced with
the same disease again
• Immunology is the study of physiological
mechanisms that humans and other animals use
to defend their bodies from invading organisms
e.g bacteria, viruses, fungi, parasites and toxins
Definition of terms
1. Antigen: any molecule that binds to immunoglobulin
or T cell receptor e.g. bacteria, fungi, viruses, cancer
cells and toxins
2. Pathogen: Microorganisms that can cause disease
3. Antibody: a toxin or other foreign substance that
induces an immune response; produced in response
to a specific antigen
4. Immunoglobulin (Ig): antigen binding molecules of B
cells
5. Vaccination: deliberate induction of protective
immunity to a pathogen
6. Immunization: The ability to resist infection
Cells of the immune system
• White blood cells also called leukocytes are
the cells of the immune system
• All leukocytes are produced and derived from
the hematopoietic stem cell in the bone
marrow
• They are found throughout the body; in blood
lymphatic system and tissues
• Types of leukocytes:
–Monocytes
–Granulocytes: neutrophils, basophils,
eosinophils
–Lymphocytes: B lymphocytes, T
lymphocytes and natural killer cells
Organs of the immune system
The cells involved in the immune response are effectively
organized into tissues and organs. The major lymphoid
organs are classified into either primary or secondary
organs
• Primary lymphoid organs (thymus and bone marrow)
are the major sites of lymphocyte development
(lymphopoiesis).
• Secondary lymphoid organs (spleen, lymph nodes,
mucosal associated lymphoid tissue) provide the
environment for the proliferation and maturation of
cells involved in the adaptive immune response
Lines of defense
Ct. Lines of defense
When a foreign antigen is introduced into an
animal, the animal will respond
immunologically to it using either of the two
lines of defense.
1. Innate immunity (non specific)-first line of
defense
2. Adaptive immunity or Acquired immunity
(Specific)- second line of defense
1. Innate immunity (non specific)-first
line of defense
• It is an antigen-independent (non-specific)
defense mechanism that is used by the host
immediately or within hours of encountering
an antigen.
• It has no immunologic memory and,
therefore, it is unable to recognize or
“memorize” the same pathogen should the
body be exposed to it in the future.
Involves;
1. Barriers:
–Skin (epidermis and dermis)
–Mucous membranes: respiratory, GI,
genitourinary tracts
–Lacrimal apparatus; tears
–Saliva
2. Chemical:
–Sebum: acids
–Perspiration; lysozyme
–Gastric juice
–Urine
The skin
• Serves both as mechanical and chemical
barrier
• Microorganisms normally associated with skin
prevent potential pathogens from colonizing
• Sebaceous glands secrete fatty acids and lactic
acid which lower the skin PH (PH 4-6)
• Unbroken skin is a contiguous barrier
Mucosal membranes
• Consist of epithelial layers and underlying
connective tissue layer
• Mucosal membranes of respiratory tract contains
hair like projections called cilia that remove
microbes inhaled through the nose and mouth
• Mucus secreted by goblet cells prevent the
microbes from associating too closely with the
cells
• Mucous membrane’s microbial activity owed due
to presence of lysozyme, mucopeptide and
secretory immunoglobulin A
Lacrimal apparatus
• Tear mechanically removes the foreign
particles and also contains lysozyme which
constantly baths surface of the eye.
• Lysozyme breaks the peptidoglycan layer,
causing bacteria to lyse
Saliva
• Saliva mechanically washes pathogens off
teeth and reduces the number of pathogens
• Saliva contains an antibody called secretory
immunoglobulin which coats every tooth from
harmful bacteria that may cause decay
The major functions of the innate
immune system
include:
1. Acting as a physical and chemical barrier to infectious
agents.
2. Recruiting immune cells to sites of infection, (such as
phagocytes (macrophages and neutrophils), dendritic
cells, mast cells, basophils, eosinophils, natural killer
(NK) cells and lymphocytes) to sites of infection)
through the production of chemical factors, including
specialized chemical mediators, called cytokines/
chemokines (small proteins involved in cell-cell
communication).
• Cytokine production leads to the release of
antibodies and other proteins and
glycoproteins which activate the complement
system
3. Activation of the complement cascade to
identify bacteria, activate immune cells and to
promote clearance of antibody complexes or
dead cells
4. The identification and removal of foreign
substances present in organs, tissues, the blood
and lymph, by specialized white blood cells
5. Activation of the adaptive immune system
through a process known as antigen
presentation
Cells of innate immunity
• Cells of innate immunity are majorly leukocytes
(WBC)
• Leukocytes are able to move freely and interact
with and capture cellular debris, foreign particles,
or invading microorganisms.
• Unlike many other cells in the body, most innate
immune leukocytes cannot divide or reproduce
on their own, but are the products of multipotent
hematopoietic stem cells present in the bone
marrow
The innate leukocytes include:
• Natural killer cells
• Mast cells
• Eosinophils
• Basophils
• Phagocytic cells includes macrophages,
neutrophils, and dendritic cells
1.Mast cells
• These cells reside in connective tissue and in
the mucous membranes.
• They are intimately associated with wound
healing and defense against pathogens, but
are also often associated with allergy and
anaphylaxis
2.Phagocytic cells
• The word 'phagocyte' literally means 'eating
cell'.
• These are immune cells that engulf, i.e.
phagocytose, pathogens or particles. (i.e., the
particle is now inside the cell). Once inside the
cell, The phagocytes releases lysosome that
contains enzymes and acids that kill and digest
the particle or organism
• They are also able to react to a group of highly
specialized molecular signals produced by
other cells, called cytokines.
• They include macrophages, neutrophils, and
dendritic cells
• Phagocytosis of the hosts’ own cells is
common as part of regular tissue
development and maintenance
• When host cells die, either internally induced by
processes involving programmed cell death (also
called apoptosis) or caused by cell injury due to a
bacterial or viral infection, phagocytic cells are
responsible for their removal from the affected
site.
– This helps in growth and development of new
healthy cells, phagocytosis is an important part
of the healing process following tissue injury.
a)Macrophages
• Macrophages, from the Greek, meaning "large
eaters," are large phagocytic leukocytes,
which are able to move outside of the vascular
system by moving across the walls of capillary
vessels and entering tissues in pursuit of
invading pathogens.
• In tissues, organ-specific macrophages are
differentiated from phagocytic cells present in
the blood called monocytes.
• Unlike neutrophils (which are short-lived
cells), macrophages are long-lived cells that
not only play a role in phagocytosis, but are
also involved in antigen presentation to T
cells.
• Macrophages are named according to the
tissue in which they reside. For example,
–In blood - monocytes
–In the liver are called Kupffer cells
–In the connective tissue are termed
histiocytes
–Dust cells (within pulmonary alveolus),
–Microglial cells (neural tissue),
–Epithelioid cells (granulomas),
–Osteoclasts (bone),
–Mesangial cells (kidney)
• Macrophages are the most efficient phagocytes,
and can phagocytose substantial numbers of
bacteria or other cells or microbes.
• The binding of bacterial molecules to receptors
on the surface of a macrophage triggers it to
engulf and destroy the bacteria .
• Pathogens also stimulate the macrophage to
produce chemokines, which summons other cells
to the site of infection
b)Neutrophils
• Neutrophils, along with two other cell types;
eosinophils and basophils are known as:
–Granulocytes due to the presence of
granules in their cytoplasm, or as
–Polymorphonuclear cells (PMNs) due to
their distinctive lobed nuclei.
• Neutrophils are the most abundant type of
phagocyte, normally representing 50 to 60% of
the total circulating leukocytes, and are usually
the first cells to arrive at the site of an infection
• In addition to their phagocytic properties,
neutrophils contain granules that, when released,
assist in the elimination of pathogenic microbes
by killing or inhibiting growth of bacteria and
fungi
• The bone marrow of a normal healthy adult
produces more than 100 billion neutrophils
per day, and more than 10 times the number
per day during acute inflammation.
c)Dendritic cells
• Dendritic cells are phagocytic cells present in
tissues that are in contact with the external
environment, mainly;
–The skin (where they are often called
Langerhans cells)
–The inner mucosal lining of the nose, lungs,
stomach, and intestines.
• They resemble neuronal dendrites in shape
but are not connected to the nervous system.
• Dendritic cells are very important in the
process of antigen presentation, and serve as
a link between the innate and adaptive
immune systems
3.Basophils and eosinophils
Basophils
When activated by a pathogen encounter, basophils
release histamine that plays a role in allergic
reactions (such as asthma).
• Unlike mast cells, which generally reside in
the connective tissue surrounding blood
vessels, basophils reside in the circulation.
– Along with mast cells, basophils also control
mechanisms associated with allergy and
asthma.
eosinophils
• Play an important role in the destruction of
parasites that are too large to be phagocytosed.
• Upon activation, eosinophils secrete a range of
highly toxic proteins and free radicals that are
highly effective in killing bacteria and parasites,
but are also responsible for tissue damage
occurring during allergic reactions.
• This process is tightly regulated to prevent any
inappropriate tissue destruction.
4.Natural killer cells
• Natural killer cells, or NK (also known as large
granular lymphocytes (LGLs) cells, are a
component of the innate immune system that
does not directly attack invading microbes.
• Rather, NK cells destroy compromised host
cells, such as tumor cells or virus-infected
cells, recognizing such cells by a condition
known as "missing self."
• This term describes cells with low levels of a cell-
surface marker called MHC I (major
histocompatibility complex) - a situation that can
arise in viral infections of host cells.
• NK cells play a major role in the rejection of
tumours and the destruction of cells infected by
viruses.
• Destruction of infected cells is achieved through
the release of perforins and granzymes from NK-
cell granules which induce apoptosis
(programmed cell death)
• They were named "natural killer" because of
the initial notion that they do not require
activation in order to kill cells that are
"missing self.”
2.Adaptive immunity or Acquired immunity
(Specific)- second line of defense
• Is antigen-dependent and antigen-specific;
• It has the capacity for memory, which enables
the host to mount a more rapid and efficient
immune response upon subsequent exposure
to the antigen. This is its hallmark
• It takes a longer time to build
• Involves the T and B cells
• Humoral immunity (mediated by B cells) and
cell mediated immunity (mediated by T cells)
• It has the ability to distinguish between self
and non-self
Second line of defense;
• Phagocytosis
• Inflammation
• Complement
• Interferon
phagocytosis
Process of phagocytosis involves:
• Phagocytosis of enemy cell (antigen)
• Fusion of lysosome and phagosome
• Enzymes start to degrade enemy cell
• Enemy cell broken into small fragments
• Fragments of antigen presented on APC
surface
• Leftover fragments released by exocytosis
Interferon (INF)
• Interferon are proteins released by virus
infected cells and which react with uninfected
cells so as to render them resistant to
infection by viruses
• The name originates from the fact that they
interfere with viral infection
• Produced by fibroblast, macrophages,
plasmacytoid cells
• Are of three types, alpha, beta and gamma
interferons:
– ᾳ interferons are produced by B lymphocytes and
Monocytes
– β interferons are produced from fibroblasts and
epithelial cells
– ϒ interferons are produced by t cells
Complement system
Is a biochemical reaction of the immune system
that helps, or “complements”, the ability of
antibodies to clear pathogens or marks
pathogens for destruction by other cells
(phagocytes).
The cascade is composed of many plasma
proteins, synthesized in the liver
Basic functions of the complement
system
– Opsonization – coats pathogens ‘tagging’ them for
destruction and this enhances phagocytosis of the
antigens
– Chemotaxis – attracting macrophages and
neutrophils (trigger recruitment of inflammatory
cells)
– Cell lysis – rupturing membranes of foreign cells
– Agglutination – clustering and binding pathogens
together
– Clearing antigen/ antibody complexes and dead cells
Inflammation
• It is defined as a programmed local tissue
response to local injury or tissue damage
• Inflammation is one of the first protective
responses to infection or irritation.
• It is stimulated by chemical factors released by
injured cells and serves to establish a physical
barrier against the spread of infection, and to
promote healing of any damaged tissue
following the clearance of pathogens
Signs of inflammation
• Rubor (redness)
• Tumor (swelling)
• Calor (heat)
• Dolor (pain)
• Functiolaesa (loss of function)
NB: the first four are referred to as the four
cardinal signs
Types of inflammation
• Acute inflammation
• Chronic inflammation
• Chronic active inflammation
• The process of acute inflammation is initiated
by cells already present in all tissues, mainly
resident macrophages, (dendritic cells,
histiocytes, Kupffer cells, and mastocytes).
• At the onset of an infection, burn, or other
injuries, these cells undergo activation and
release inflammatory mediators responsible
for the clinical signs of inflammation.
• Chemical factors are produced during
inflammation (histamine, bradykinin,
serotonin, leukotrienes, and prostaglandins)
sensitize pain receptors, cause vasodilation of
the blood vessels at the scene, and attract
phagocytes, especially neutrophils.
Type 1 hypersensitivity
• Type 1 hypersensitivity reaction is commonly
called allergic or immediate hypersensitivity
reaction
• Type 1 reaction is always rapid, occurring
within minutes of exposure to an antigen, and
always involves IgE-mediated degranulation of
basophils or mast cells
• Type 1 reactions are also known as IgE-
mediated hypersensitivity reaction
• IgE is responsible for sensitizing mast cells and
providing recognition of antigen for
immediate hypersensitivity reactions
• Normaly occur in two forms: anaphylaxis and
atopy
Anaphylaxis:
• acute potentially fatal and systemic manifestation
of immediate hypersensitivity reaction
• It occurs when an antigen (allergen) binds to IgE
on the surface of mast cells with the consequent
release of several mediators of anaphylaxis
• Binding of IgE to the mast cells is also known as
sensitization, because IgE –coated mast cells are
ready to be activated on repeat antigen
encounter
• The initiater of type 1 reaction is otherwise
known as an allergen
• Examples or allergens: plant pollen, proteins,
certain food items (eggs, milk, seafood), nuts,
drugs (e.g. penicillin, sulphonamides, aspirin,
local anesthetics, animal hair e.t.c.
Mediators of anaphylaxis
• Histamine
• Slow reacting substances of anaphylaxis (SRS-
A) i.e. leukotrienes
• Serotonin
• Eosinophilic Chemotactic Factors of
Anaphylaxis
• Prostaglandins and Thromboxanes
histamine
• It is the most important mediators of
anaphylaxis
• It is found in a preformed state in granules of
mast cells and basophils
• Causes vasodilatation, increased capillary
permeability and smooth muscle contraction
• It is the principal mediator of allergic rhinitis,
urticaria, and angioedema
Clinical manifestations of anaphylaxis
• Anaphylaxis is an acute, life-threatening reaction
usually affecting multiple organs
• The time of onset of symptoms depends on the level of
hypersensitivity and amount, diffusibility and site of
exposure to the antigen
Organs involved:
• Skin: pruritus, flushing, urticarial, angioedema
• Respiratory tract: bronchospasm and laryngeal edema
• Cardiovascular system: hypotension an cardiac
arrhythmias
Atopy
• Recurrent non-fatal and local manifestation of
immediate hypersensitivity reaction
• Localized to a specific tissue, often involving
epithelial surfaces at the site of antigen entry
• Mediated by IgE antibodies; atopic individuals
produce high levels of IgE in response to allergens
as against the normal individuals who do not
• Common manifestations are: asthma, rhinitis,
urticarial and atopic dermatitis
Type II(cytotoxic) hypersensitivity
• Mediated by antibodies directed against antigens
on the cell membrane that activates complement
thereby causing antibody mediated destruction
of cells
• The cell membrane is damaged by a membrane
attack complex during activation of the
complement
• The reactions involve combination of IgG or IgM
antibodies with the cell-fixed antigens or
alternatively circulating antigens absorbed into
cells
• Antigen antibody reaction leads to
complement activation resulting to formation
of membrane attack complex
• Antibody-dependent cell-mediated
cytotoxicity (ADCC) is another mechanism
which involves the binding of cytotoxic cells
with Fc receptors in the Fc binding part of the
antibodies coating the target cells
• In type II reactions, the antigens may be blood
platelets, red or white blood cells with drugs
attached to their surface and the immune
response may thus cause thrombocytopenia,
hemolytic anemia or agranulocytosis
Examples of type II
• AB and Rh blood group reactions:
Transfusion reactions
Erythroblastosis fetalis (hemolytic disease of
newborns
• Autoimmune disease such as:
Rheumatic fever where antibodies result in joint and
heart valve damage
Idiopathic thrombocytopenic purpura where
antibodies result in the destruction of platelets
• Transplant rejection
• Drug induced hemolysis
Innate Adaptive
Definition Immediate protective response that
does not require previous exposure to
antigen
Immune resp
a specific ant
Type of
defense
Nonspecific immune response; can be
first line or second line of defense
specific: Seco
defense
Differences between Innate and
adaptive immunity
nnate immunity Adaptive immunity
ormal flora, physical
arriers, chemical barriers,
hagocytes, histamine,
nflammation, fever,
omplement proteins
Humoral and cell mediated immunity
hagocytes such as
macrophages, neutrophils,
atural killer cells,
monocytes, mast cells and
endritic cells
Lymphocytes and antigen presenting cells
hey don’t have memory
ecause they don’t generate
mmunological memory
They have long term memory because they ge
immunological memory
Innate Adaptive
Effectiveness Less effective than
adaptive
More effectiv
Presence Present at birth Created in re
foreign subst
Response Rapid or quick response Slow respons
Inheritance Inherited from parents
and passed to offsprings
Cannot be inh
Innate immunity Adaptive im
system involvement Alternative and lectin
pathways
Classical pathwa
antigen Genetically determined, no
prior exposure or antibody
production
Produced by prio
antibody produc
ion None Immediate and d
hypersensitivity
Microbes Microbes and no
agents (antigens
Passive and active immunity
• Active immunity:
Naturally acquired active immunity
Artificially acquired active immunity
• Passive immunity:
Naturally acquired passive immunity
Artificially acquired passive immunity
Active immunity
• Naturally acquired:
–Infection after contact with pathogens
• Artificially acquired:
–Vaccine; dead or attenuated pathogens
Passive immunity
• Naturally acquired:
Antibodies passed from mother to fetus via
placenta, or infant in milk
• Artificially acquired:
Injection of immune serum (gamma
globulin)
Herd immunity
• Also referred to as Herd effect, community
immunity, population immunity or social
immunity
• Protection from disease in a group, due to a large
enough proportion of the population having
immunity to prevent the disease from spreading
from person to person
• It is the reduced probability of an individual
becoming infected when part of a vaccinated
population
• Protection by herd immunity applies to
vaccinated as well as unvaccinated individuals
• The chance of becoming infected in a
population decreases with increasing density
of individuals being vaccinated
• Individuals who are immune to a disease act
as a barrier in the spread of disease
Continuation of Adaptive
Immunity
Also Called Acquired or Specific
Immunity
Adaptive immunity
• Usually awakened when innate immunity is
ineffective in eliminating infectious agents and
the infection is established
Primary functions of adaptive immunity include:
• The recognition of “non-self” antigens in the
presence of “self” antigens
• The generation of pathogen/ antigen-specific
immunologic pathways that eliminate specific
pathogens or pathogen infected cells
• The development of an immunologic memory
that can quickly eliminate a specific pathogen
should subsequent infections occur
The cells of the adaptive immune system
• The cells of the adaptive immune system are:
– T lymphocytes and
– B lymphocytes.
• They are a subset of leukocytes, derived from
the same multipotent hematopoietic stem cells
Congenital immunodeficiency diseases are often caused by blocks
at different stages of lymphocyte maturation
Development of B and T lymphocytes
Classes of lymphocytes
Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier
• The peripheral lymphoid organs contain a mixture
of B and T cells in at least three stages of
differentiation:
– Naive cells that have not matured, left the bone
marrow or thymus, have entered the lymphatic
system, but that have yet to encounter their specific
antigen,
– Effector cells that have been activated by their
specific antigen and are actively involved in
eliminating a pathogen.
– Memory cells – the long-lived survivors of past
infections.
Adaptive cont’
• B lymphocytes – are involved in
‘humoral’ or ‘antibody mediated’
immunity
• T lymphocytes – are involved in ‘cell
mediated’ immunity
Different types
of immune
responses are
mediated by
different classes
of lymphocytes
and defend
against different
types of microbes
Types of adaptive immunity
Cell-mediated immunity does not involve antibodies,
but rather protects an organism through :
– The activation of antigen-specific cytotoxic T cells that
induce cell death
– The activation of macrophages and NK cells
– The stimulation of cytokine production
Cell-mediated immunity is directed primarily at
microbes that survive in host cells. This type of
immunity is most effective in eliminating virus-
infected cells, but can also participate in defending
against fungi, protozoa, cancers, and intracellular
bacteria.
Phases of adaptive immune responses
T lymphocytes
.
T Lymphocytes and Antigen Presenting Cells (APCs)
• T cells derive from hematopoietic stem cells
in bone marrow and migrate to mature in the
thymus.
• These cells express a unique antigen-binding
receptor on their membrane, known as the T-
cell receptor (TCR)
• They require the action of APCs (usually
dendritic cells, macrophages, B cells and
epithelial cells) to recognize a specific
antigen.
APCs
• APCs include Dendritic cells, B-cells and
macrophages
They are equipped with special chemicals
recognized by T Cell receptors on T
lymphocytes
Antigen presentation stimulates T cells to become
either
• “T - cytotoxic“ or CD8+ cells
• “T - helper" or CD4+ cells.
• T regulatory cells
Exogenous antigen presentation
• Dendritic cells engulf exogenous pathogens, such as
bacteria or toxins in the tissues and then migrate to the
T cell-enriched lymph nodes.
• During migration, dendritic cells develop an ability to
communicate with T-cells.
• The dendritic cell uses enzymes to chop the pathogen
into antigen pieces. In the lymph node, the dendritic
cell will display these "non-self" antigens on its surface
by coupling them to a "self"-receptor called the major
histocompatibility complex (MHC) (also known in
humans as Human leukocyte antigen (HLA)).
• This MHC: antigen complex is recognized by T-cells
passing through the lymph node which activate CD4+
helper T-cells.
Endogenous antigen presentation
• Endogenous antigens are produced by
intracellular bacteria and viruses replicating
within a host cell.
• The host cell uses enzymes to digest virally
associated proteins, and displays these pieces
on its surface to T-cells by coupling them to
MHC.
• Endogenous antigens are typically displayed
on MHC molecules and activate CD8+
cytotoxic T-cells.
T Lymphocytes
• CD8 or T cytotoxic lymphocytes
• CD4 or T Helper lymphocytes
• Regulatory T cells (T suppressor cells)
CD8+ T lymphocytes or cytotoxic T
lymphocytes
• Cytotoxic T cells (also known as CD8, killer T
cell, or cytotoxic T-lymphocyte (CTL)) are a sub-
group of T cells that induce the death of cells
that are infected with viruses (and other
pathogens), or are otherwise damaged or
dysfunctional cells
– Naive T cells are activated when their T-cell receptor (TCR)
strongly interacts with MHC – antigen complex on APCs
and is what keeps the CTL and infected cell bound
together.
– Once activated, the CTL gains functionality, and divides
rapidly, to produce an army of “armed”-effector cells.
Activated CTL will then travel throughout the body in
search of cells bearing that unique MHC + antigen
complex
• When exposed to these infected or dysfunctional
host cells, effector CTL release perforin and
granulysin: cytotoxins that form pores in the
target cell's plasma membrane and causing it to
burst or lyse.
• CTL also releases granzyme that enters cells via
pores to induce apoptosis (cell death).
– To limit extensive tissue damage during an infection,
CTL activation is tightly controlled and in general
requires a very strong MHC/antigen activation signal,
or additional activation signals provided by "helper"
T-cells
• Upon resolution of the infection, most of the
effector cells will die and be cleared away by
phagocytes, but a few of these cells will be
retained as memory cells.
• Upon a later encounter with the same
antigen, these memory cells quickly
differentiate into effector cells, dramatically
shortening the time required to mount an
effective response
Helper T-cells/ CD4+
• Are immune response mediators that play
an important role in establishing and
maximizing the capabilities of the acquired
immune response
• These cells have no cytotoxic or phagocytic
activity; and cannot kill infected cells or
clear pathogens, but, in essence "manage"
the immune response, by directing other
cells to perform these tasks.
• Helper T cells express T cell receptors (TCR)
that recognize antigen bound to I MHC
molecules.
• The activation of a naive helper T-cell causes
it to release cytokines, which influences the
activity of many cell types, including the APC
(Antigen-Presenting Cell) that activated it.
• Helper T-cells require a much milder
activation stimulus than cytotoxic T cells.
• They can provide extra signals that "help"
activate cytotoxic cells.
Types of CD4+ T helper cells responses
Two types of effector CD4+ T helper cell
responses can be induced by a
professional APCs,
• T helper 1 ( Th1) and
• T helper 2 (Th2)
Each designed to eliminate different types
of pathogens
• The Th1 response
–Is characterized by the production of mediators
(interferons) which activates the bacteriacidal
activities of macrophages, and induces B cells to
make opsonizing (coating) and complement-
system antibodies, and leads to "cell-mediated
immunity”.
• The Th2 response
–Is characterized by the release of Mediators
(interleukins), which results in the activation of B
cells to make neutralizing antibodies, leading to
"humoral immunity” or “antibody mediated
immunity”
• ]In general, Th1 responses are more effective
against intracellular pathogens (viruses and
bacteria that are inside host cells), whereas
Th2 responses are more effective against
extracellular bacteria, parasites including
helminths and toxins.
• Like cytotoxic T cells, most of the CD4+
helper cells will die upon resolution of
infection, with a few remaining as CD4+
memory cells
What is unique about HIV?
.
HIV
• HIV is able to weaken the immune
system by attacking the CD4+ T cells,
precisely the cells that could drive the
destruction of the virus,
• CD4 are also the cells that drive
immunity against all other pathogens
encountered during an organism's
lifetime.
Regulatory T cells (T-reg)/ suppressor
cells
• Limits and suppresses the immune
system, and may control abnormal
immune responses to self-antigens; an
important mechanism in controlling the
development of autoimmune diseases.
conclusion
T cells contribute to immune defenses in
two major ways:
• Some direct and regulate immune
responses – T helper or CD4 cells
• Others directly attack infected or
cancerous cells – T cytotoxic or CD8 cells
B Lymphocytes
Humoral immunity
• B cells arise from hematopoietic stem cells in
the bone marrow, mature and leave the
marrow expressing a unique antigen-binding
receptor on their membrane.
• Unlike T cells, B cells can recognize free
antigen directly, without the need for APCs.
The principal function of B cells is the
production of antibodies against foreign
antigens.
B lymphocytes and antibody
production
• B Cells are the major cells involved in the creation
of antibodies that circulate in blood plasma and
lymph, known as humoral immunity.
• Antibodies (also known as immunoglobulin, Ig),
are large Y-shaped proteins used by the immune
system to identify and neutralize foreign objects
• In mammals there are five types of antibody: IgA,
IgD, IgE, IgG, and IgM, differing in biological
properties
B cell continued
• Upon activation, B cells produce antibodies, each
of which recognizing a unique antigen, and
neutralizing specific pathogens.
• Like the T cell, B cells express a unique B cell
receptor (BCR).
• All the BCR of any one type of B cells recognizes
and binds to only one particular antigen.
• A critical difference between B cells and T cells is
that whereas T cells recognize their cognate
antigen in a processed form coupled to the MHC
molecule, B cells recognize antigens in their
native/ original form
• Once a B cell encounters its cognate (or specific)
antigen (and receives additional signals from a
helper T cell (esp Th2 type), it undergoes
proliferation and differentiate into effector cells
called:
– Antibody-secreting plasma cells
– Memory B cells
Phases of lymphocyte activation
Proliferation keeps pace with replicating microbes (e.g. 1 B cell
--> 4,000 Ab-secreting cells --> ~1012 antibody molecules/hour)
Differentiation: converts lymphocytes into effective defenders
Antibody Secreting Plasma Cells
• Plasma cells are short-lived cells (2–3 days)
that secrete antibodies. These antibodies bind
to antigens, making them easier targets for
phagocytes, and trigger the complement
system.
• Plasma cells do not have antigen-binding
receptors. These are short-lived cells that
undergo apoptosis when the inciting antigen
that induced the immune response is
eliminated.
• The secreted antibodies bind to antigens on the
surface of pathogens, flagging them for
destruction through pathogen and toxin
neutralization, complement activation, opsonin
promotion of phagocytosis and pathogen
elimination.
• Upon elimination of the pathogen, the antigen-
antibody complexes are cleared by the
complement system.
Five types of antibodies are produced by B cells:
• Immunoglobulin A (IgA)
• Immunoglobulin D (IgD)
• Immunoglobulin E (IgE)
• Immunoglobulin G (IgG) and
• Immunoglobulin M (IgM).
Each of these antibodies has differing biological
functions and recognize and neutralize specific
pathogens.
• Antibodies play an important role in containing
virus proliferation during acute phase when viruses
are still in circulation. However, they are not
generally capable of eliminating a virus once
viruses infect cells.
• Once an infection is established, cell-mediated
immune mechanisms are most important in host
defense. B cells act as APC to T cells
• About 10% of plasma cells will survive to become
long-lived antigen-specific memory B cells
Memory B cells
• Memory B cells are “long-lived” survivors of
past infection and continue to express
antigen-binding receptors.
• These cells can be called upon to respond
quickly and eliminate an antigen upon re-
exposure while the host experiences few, if
any, symptoms
Primary and secondary immune responses illustrate
specificity and memory in adaptive immunity
Antibodies
• The terms antibody/ immunoglobulin are
found in the blood and tissue fluids, as well as
many secretions.
• In structure, they are large Y-shaped globular
proteins.
• There are five types of antibody: IgA, IgD, IgE,
IgG, and IgM. Each differs in its biological
properties and deals with different antigens.
• Antibodies are synthesized and secreted by
plasma cells that are derived from the B cells
of the immune system.
Antibodies contribute to immunity in three
ways:
–They prevent pathogens from entering or
damaging cells by binding to them;
–They stimulate removal of pathogens by
macrophages and other cells by coating
the pathogen; and
–They trigger destruction of pathogens by
stimulating other immune responses such
as the complement pathway
• Each antibody recognizes a specific antigen
unique to its target.
• By binding their specific antigens,
–Antibodies can cause agglutination and
precipitation of antibody-antigen products,
prime for phagocytosis by macrophages and
other cells,
–Block viral receptors,
–Stimulate other immune responses, such as the
complement pathway.
Example of antibody – antigen
reaction
• An incompatible blood transfusion causes a
transfusion reaction, which is mediated by the
humoral immune response. This type of
reaction, called an acute hemolytic reaction,
results in the rapid destruction (hemolysis) of
the donor RBCs by host antibodies. The
symptoms are fever and chills, back pain and
pink or red urine (hemoglobinuria). The major
complication is that hemoglobin released by
the destruction of RBCs can cause acute renal
failure
Antibodies
IgA
• Found in secretions in mucosal areas, such
as the gut, respiratory tract and urogenital
tract, and prevents colonization by
pathogens. Also found in saliva, tears, and
breast milk.
IgD
• It has been shown to activate basophils
and mast cells to produce antimicrobial
factors.
IgE
• Binds to allergens and triggers histamine release from
mast cells and basophils, and is involved in allergy.
• Also protects against parasitic worms
IgG
• Provides the majority of antibody-based immunity
against invading pathogens. Most abundant antibody
(70-80% of all Ig).
• The only antibody capable of crossing the placenta to
give passive immunity to the fetus
IgM
• Found on the surface of B cells and in circulation.
• Eliminates pathogens in the early stages of B cell-
mediated (humoral) immunity before there is sufficient
IgG.
• Humans also produce "natural antibodies"
that are present in serum before microbial
infection.
• Natural antibodies have been defined as
antibodies that are produced without any
previous infection, vaccination, other foreign
antigen exposure or passive immunization.
– These antibodies can activate the classical complement
system leading to lysis of enveloped bacteria and viruses
particles long before the adaptive immune response is
activated
Antibody-mediated (Humoral) vs. cell-
mediated immunity
• Humoral immunity – Immunity provided
through antibodies
• Cell mediated immunity does not involve
antibodies, but works through:
–Activation of Ag-specific cytotoxic T cells
–Activation of macrophages and NK cells,
to destroy intracellular pathogens
- The stimulation of cytokine production
• Cell-mediated immunity is most effective in
eliminating virus-infected cells, but can also
participate in defending against fungi, protozoa,
cancers, and intracellular bacteria. It plays a big
role in transplant rejection
Passive vs. Active immunization
• Acquired immunity is attained through either passive or
active immunization
Passive immunization refers to the transfer of active humoral
immunity, in the form of “ready-made” antibodies, from one
individual to another.
• It can occur naturally by transplacental transfer of maternal
antibodies to the developing fetus, or
• It can be induced artificially by injecting a recipient with
exogenous antibodies targeted to a specific pathogen or
toxin.
– This is used when there is a high risk of infection and
insufficient time for the body to develop its own immune
response
• Active immunization refers to the
production of antibodies against a specific
agent after exposure to the antigen.
• It can be acquired through either
– Natural infection with a microbe or
– Through administration of a vaccine that can consist
of attenuated (weakened) pathogens or inactivated
organisms,
Active and passive immunity
Active immunity: long-lasting protection (memory),
multiple effector mechanisms activated, lag time
Passive immunity: rapid protection, short duration
Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011
Immunopathology
Defects or malfunctions in either the innate
or adaptive immune response can provoke
illness or disease.
Such disorders are generally caused by:
• An overactive immune response (known
as hypersensitivity reactions)
• An inappropriate reaction to self (known
as autoimmunity)
• Ineffective immune responses (known as
immunodeficiency).
Hypersensitivity reactions
Hypersensitivity reactions refer to undesirable
responses produced by the normal immune
system.
There are four types of hypersensitivity reactions
• Type I: immediate hypersensitivity
• Type II: cytotoxic or antibody-dependent
hypersensitivity
• Type III: immune complex disease
• Type IV: delayed-type hypersensitivity
Type I - immediate hypersensitivity (anaphylaxis)
– Antibodies (igE)bind to certain cells, causing re-
lease of chemical substances that produce an
inflammatory reaction. E.g Extrinsic asthma,Hay
fever
Type II - Cytotoxic or antibody dependent rx
– Antibodies cause activation of complement system,
which leads to tissue damage. Examples
Transfusion reaction, ABO incompatibility,
Hemolytic disease of the newborn
Type III - Immune-complex reactions
– Immune complexes are deposited in tissues, where they
activate complement which results in a generalized
inflammatory reaction. Examples Acute
glomerulonephritis, Serum sickness
Type IV - Delayed reactions
– Antigens stimulate T cells that release lymphokines,
which cause inflammation and tissue damage. Examples
Contact dermatitis, Tuberculin skin test, Graft-versus-
host disease, Allograft rejection
Autoimmunity
• Autoimmunity involves the loss of normal immune
homeostasis such that the organism produces an
abnormal response to its own tissue.
• The hallmark of autoimmunity is the presence of self-
reactive T cells, auto-antibodies, and inflammation.
• Prominent examples of autoimmune diseases include:
– Celiac disease – Small intestines
– Type 1 diabetes mellitus – Islets of Langerhan
– Addison’s disease – Adrenal gland
– Graves’ disease – Thyroid gland
Immunodeficiency
• Refers to a state in which the immune
system's ability to fight infectious disease is
compromised or entirely absent.
• Immunodeficiency disorders may result from
a primary congenital defect (primary
immunodeficiency) or may be acquired from
a secondary cause (secondary
immunodeficiency), such as viral or bacterial
infections, malnutrition or treatment with
drugs that induce immunosuppression.
• Certain diseases can also directly or
indirectly impair the immune system such as
leukemia and multiple myeloma.
• Immunodeficiency is also the hallmark of
acquired immunodeficiency syndrome
(AIDS), caused by the human
immunodeficiency virus (HIV).
• HIV directly infects Th cells and also impairs
other immune system responses indirectly.

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combined notes on microbiology and immunolgy.pptx

  • 1. Combine Notes Microbiology And Immunology welcome
  • 2. Course outline Microbiology • Historical background • Classification & properties of microorganisms • Clinical importance of micro-organisms • Sources of micro-organisms
  • 3. • Modes of transmission of infections • Concept of infection (definition of terms related to infection; stages of development of infection; common nosocomial infections)
  • 4. Immunology Types of immunity;  humoral cell mediated Passive active herd immunity
  • 5. • Antigen-antibody reaction • Types of antibodies • Modes of action of antibodies • Complement system of immunity
  • 6. MICROBIOLOGY • Microbiology is the study of organisms too small to be seen by the naked eye • Microbiology is the branch of science that deals with the study of micro organisms • these organisms include viruses, bacteria, fungi and protozoa
  • 7. • Medical microbiology is the study of causative agents of infectious diseases of humans and their reaction to such infections • it deals with etiology, pathogenesis, laboratory diagnosis, specific treatment and control of infection (immunization) • It deals with microbes-the causative agent of infectious diseases
  • 8. Historical background Microbiology had its beginning in the ancient times with an awareness in sanitation ( Hippocrates) Historical eras of microbiology 1. Biblical times- 1500 BC Levitical law with strict laws concerning sanitation, an diseases like leprosy 2. Ancient times of the Greeks and Romans – 146- 476 AD They insisted on sewage systems, clean water, regular bathing, latrines and ventiltion
  • 9. Dark ages ( 400 AD- 1100 AD) This was a period of loss of knowledge and practice was based on superstition and forces 4. Renaissance/ Enlightment age-1200 AD-1700AD There was a hunger for knowledge and reasons and facts became the basis for actions and procedures 5. Golden Age- 1800 AD This was the advent of microbiology and microscopy
  • 10. Principal Contributors to Microbiology 1674 Anton Van Leeuwenhoek • Dutch biologist – was the first man to observe bacteria and other microorganisms using a single lens microscope of his own design and drew them and documented them, forming the basis of microbiology 1796 Edward Jenner • using ancient Chinese technique for small pox vaccination developed a method of using cowpox to immunize a child against small pox. The same principles are used for developing vaccines today
  • 11. 1840 Friedrich Henle • proposed a criteria for proving that microorganisms caused human diseases (germ theory of disease) 1857 Louis Pasteur • Father of modern medicine • He was a French chemist who disapproved the theory of spontaneous generation
  • 12. • He proved that lactic fermentation was due to living organisms and based on experiments proved that fermentation of wine was caused by bacteria • designed vaccines against anthrax, cholera and rabies as well as pasteurization for food preservation.
  • 13. 1867 • Joseph Lister; father of antiseptic surgery; first to sterilize instruments and reduce infections 1884 • Hans Christian Gram; developed a method of staining bacteria to make them visible under a microscope
  • 14. 1842-1910 Robert Koch • German physician • Studied the disease anthrax • Developed a method to identify the etiologic agent • First to identify Bacillus anthracis as etiologic agent to anthrax (1877) • Developed a set of postulates
  • 15. The germ theory of disease • States that micro-organisms known as pathogens or “germs” can lead to disease. These small organisms, too small to see without magnification, invade humans, other animals and other living hosts. • Their growth and reproduction within their hosts can cause disease.
  • 16. Scope and Importance of microbiology • Production of antibiotics e.g. penicillin from penicillium • Production of enzymes, vaccines, biosurfactants, alcoholic and other pharmaceutical products • Diagnosis of disease and treatment e.g. ELISA, widal test • Treatment of industrial waste material • Plant growth promotion
  • 17. • Sterile product preparation and Sterilization(process of killing microorganisms) • Identification of microorganisms e.g. morphological, cultural or microscopic study • Testing of pharmaceutical products and raw materials
  • 18. Importance of microbiology in nursing • Helps the nurse to know pathogens, their sources and composition • Helps to know how these micro organisms are transmitted and how they spread diseases • It is a step in prevention and cure of many diseases • Helps the nurse to take universal precautions when in the hospital environment • It an important aspect in infection control • Forms a rich source in health education, immunization and surveillance
  • 19. Definitions of term • Ecology – relations of microorganisms to one another and to their physical surroundings • Saprophytes – a term used for plants, fungi or bacteria which obtain nutrients from dead organic matter • Symbiosis – the relationship between 2 different kinds of organisms living in close physical association to the advantage of both
  • 20. sometimes referred to as mutualism e.g. gut protozoa in herbivores – receive nutrients, help animals digest, nitrogen fixing bacteria that live in the roots of legumes, lactobacillus in stomach • Commensal - an organism living with, on or in another without causing injury. Refers to a relationship in which one organism derives food and other benefits from another without hurting or helping it e.g normal flora in the mouth
  • 21. Parasite • an organism that obtains shelter and nourishment on another organisms (host). It is a non mutual relationship where one species benefits at the expense of the other • They are capable of causing harm and disease to their host and are generally much smaller than their host e.g Macroparasites -ticks, lice, tapeworm or microparasites- bacteria, viruses, fungi
  • 22. • Pathogen – microorganism capable of causing disease • Virulence – the degree of pathogenicity of an organism or measure of the ability of an organism to cause disease • Pathogens/causative agent: Microbes that are capable of causing disease are called pathogenic.
  • 23. • Infectious disease process: The interaction be tween the pathogen microorganism, the envir onment and the host • An infection: when pathogen invades the bod y and the conditions are favorable for it to mul tiply and cause injurious effects or disease.
  • 24. • Vaccine: an antigenic substance prepared fro m the causative agent of a disease or a synthe tic substitute, used to provide immunity again st one or several diseases • Incubation period – the time between exposu re to a pathogenic organism and when first sy mptoms apparent
  • 25. Modes of transmission of microorganisms Direct transmission: • Direct contact • Droplet infection • Innoculation into skin or mucosa • Transplacental (vertical
  • 26. Indirect transmission: • Vehicle borne (water/ blood) • Vector borne • Air borne • Fomite borne
  • 27. Nosocomial infections • Nosocomial infections are also referred to as hospital acquired infections • Infections are considered nosocomial if they first appear 48hours or more after hospital admission or within 30 days after discharge
  • 28. Causes of rise in nosocomial infections • Crowded hospital conditions • New microorganisms • Increasing number of people with compromised immune system • Increasing bacterial resistance
  • 29. • Contaminated hospital environment • Contaminated instruments (invasive devices) • Medical personel; colonized infected transient carriers • Patient flora: cutaneous, gastrointestinal, respiratory, genitourinary
  • 30. Common sites of infection • Surgical wounds • Urinary tract • Skin • Respiratory tract
  • 31. Impact of nosocomial infections • Prolonged hospital stay • Additional morbidity • Increased mortality • Long-term physical and psychological consequences • Increased cost of care
  • 32. SOURCES AND SPREAD OF INFECTION Sources of infection Environmental sou rces Person- to-person Medical or surgical proce dures Self-infection Inanimate/nonlivin g objects Water, food, soil, etc. Animals (bites and scratches; zoonoses) Arthropod vectors Airborne infection Direct contact (touching, kissing, etc.) Maternal transmission (intrauterine, transplacental) Sexual transmission Instrumentation, operation s Transfusion (blood and blood products) Transplants (tissues, organs) Endogenous s ources (n ormal flor a) Shared needles Needlestick injuries Infected person or he althy carriers
  • 33. Basic classifications of microorganisms –Eukaryotic microorganisms – organisms whose cells contain a nucleus and other structures enclosed within membranes e.g. fungi, protozoa, slime moulds, algae –Prokaryotic microorganisms – is a single- celled organism that lacks a membrane- bound nucleus , mitochondria, or any other membrane-bound organelle e.g. bacteria
  • 34. Differences between prokaryote and eukaryote cells Prokaryotic cells Eukaryote cells 1. Small cell (<5µm) Larger (>10µm) 2. Always unicellular Often multicellular 3. No nucleus or any membrane bound organelles Always have nucleus and membranes bound organelles 4. DNA circular, without proteins DNA is linear and associated with proteins to form chromatin 5. Cell division is by binary fission Cell division is by meiosis and mitosis
  • 35. 6 . Ribosmes are small Ribosomes are large 7. No cytoskeleton Always have cytoskeleton 8. Motility by rigid rotating flagellum made from flagellin Motility by flexible waving cilia or flagella made from tubulins 9. Reproduction is always asexual Reproduction is sexual or asexual
  • 36. Factors promoting Growth and Development of Micro-organisms 1. Temperature: • Determines the rate of growth, multiplication, survival and death of all living organisms. • High temperatures damage microbes by denaturing enzymes, transport carriers, and other proteins; Microbial membranes are disrupted by temperature extremes; At very low temperatures, membranes also solidify and enzymes also do not function properly
  • 37. • Can be divided into: • Psychrophilles – prefer temperature of 0-5 degrees • Mesophilles - prefer temperature of 20- 45 degrees • Thermophilles – prefer temperature of above 55 degrees
  • 38. 2. PH Levels: • Refers to negative logarithm of hydrogen ion concentration • Microbial growth is strongly affected by the PH of the medium • Drastic variations in cytoplasmic PH disrupt the plasma membrane or inhibit the activity of enzymes and membrane transport proteins • Acidophiles, alkalophiles, neutrophiles; Most prefer neutral PH
  • 39. 3. Moisture – free flow of water is important to microorganisms for their cells to exchange nutrients and for metabolic processes. All microorganisms require water, some less. The more moisture, the more microorganisms will be found 4. Oxygen and nitrogen–Many microorganism require an oxygen rich environment (aerobic) but others flourish in low oxygen surroundings (anaerobic) or some can survive in either
  • 40. Classification of micro-organism • Bacteria • Viruses • Fungi • Parasites
  • 41. BACTERIA • Are unicellular prokaryocytes, have neither a well defined nucleus nor a nucleus membrane • It consists of a unique cell wall, cytoplasmic membrane enclosing the cytoplasm, mesosomes, a nucleus apparatus, ribosomes and cytoplasmic granules. Some have flagella, pili and can produce spores • They have a large surface area to volume ratio and can gain food rapidly from their environment by diffusion and active transport
  • 42. • Unlike most other organisms, bacteria have few morphological differences that can be used to classify them • Bacteria do not vary in size and shape to the extent that other types of organisms do • They reproduce by binary fission (asexually) and branching (budding)
  • 43. • Classically, bacteria have been grouped and based on structure, physiology, molecular composition and reaction to specific stains (gram stain) • The three common types of bacterial morphology are cocci/ coccus bacilli/ bacillus spirillum/spirochetes
  • 44.
  • 45. • Bacteria are classified according to their cell wall characteristics as either gram positive or gram negative. • Differences in the cell wall account for the differences in their functional properties as well as their susceptibility to antimicrobial agents. • In gram positive bacteria the cell wall called peptidoglycan forms a thick layer to the cell membrane and may contain other macromolecules.
  • 46. • In gram negative bacteria the peptidoglycan is thin and is overlaid by an outer membrane, anchored to lipoprotein molecules. • Many bacteria species are less demanding nutritionally and may require a single organic compound to meet all of their biosynthetic needs • The cell must encounter acceptable conditions of temperature, oxygen, PH, moisture and ionic strength • Some bacteria are obligate aerobes i.e. Require oxygen while others are anaerobes
  • 47. • Facultative bacteria is one that can survive in both aerobic and anaerobic conditions. • Bacteria obtain nutrients mainly by taking up small molecules across the cell wall. • In human beings the optimum PH for bacterial growth is between 7.2- 7.6.
  • 48.
  • 49. Gram staining (or Gram's method) is a method of differentiating bacterial species into two large groups (Gram- positive and Gram-negative). It is based on the chemical and physical properties of their cell walls. Primarily, it detects peptidoglycan, which is present in a thick layer in Gram positive bacteria. A Gram +ve results in a purple/blue color while a Gram -ve results in a pink/red color.
  • 50. • Gram stain is almost always the first step in the identification of a bacterial organism, and is the default stain performed by laboratories over a sample when no specific culture is referred.
  • 51. While Gram staining is a valuable diagnostic tool in both clinical and research settings, not all bacteria can be definitively classified by this technique, thus forming Gram-variable and Gram-indeterminate groups as well. The word Gram is always spelled with a capital, referring to Hans Christian Gram, the inventor of Gram staining.
  • 52. Gram-positive bacteria have a thick mesh-like cell wall made of peptidoglycan (50-90% of cell envelope), which are stained purple by crystal violet. Gram-negative bacteria, on the other hand, have a thinner layer (10% of cell envelope), which are stained pink by the counter-stain.
  • 53. There are four basic steps of the Gram stain: (i) Applying a primary stain (crystal violet) to a heat-fixed smear of a bacterial culture. Heat fixing kills some bacteria but is mostly used to affix the bacteria to the slide so that they don't rinse out during the staining procedure. (ii) The addition of a mordant, which binds to crystal violet and traps it in the cell (Gram's iodine)
  • 54. iii) Rapid decolorization with alcohol or acetone, and (iv) Counterstaining with safranin. Carbol fuchsin is sometimes substituted for safranin since it will more intensely stain anaerobic bacteria but it is much less commonly employed as a counterstain.
  • 55.
  • 56.
  • 57.
  • 58. Bacterial cell division 1. Bacteria reproduce asexually via binary fusion • Replication of bacterial chromosome triggers initiation of cell division • Cell wall extends, septum is formed • Septum grows and cleaves the daughter cell. • Incomplete cleavage of the septum can cause bacteria to remain linked forming chains – streptococcus or clusters – Staphylococcus
  • 59.
  • 60. 2. spore formation • Some gram +ve bacteria species form spores e.g Bacillus sp. and Clostridia Sp. Esp in harsh environment such as lack of nutrients • Gram –ve bacteria do not form spores • The spore has a copy of the chromosome, ribosomes and essential proteins, outer membrane, 2 peptidoglycan layers and an outer keratin like protein layer.
  • 61. • The spore protects bacterial DNA from desiccation, intense heat, radiation and attack by enzymes and chemicals • Are so resistant that they can remain viable for centuries • They are difficult to decontaminate with standard disinfectants.
  • 62.
  • 63. Bacterial metabolism • In general, bacteria require a source of carbon, nitrogen, an energy source, water and various ions for growth. Pathogenic bacteria derive energy from metabolizing sugars, fats and proteins.
  • 64. • Not all bacteria require oxygen for growth: –Obligate anaerobes – cannot grow in the presence of oxygen e.g clostridium perfringes –Obligate aerobes – require oxygen for growth e.g Mycobacterium tuberculosis –Facultative anaerobes – grow in either the presence or absence of oxygen
  • 65. Bacterial growth • For bacterial growth to occur, there must be sufficient metabolites to support synthesis of bacterial components. – When bacteria are added to a medium, they require time to adapt to the new environment before they start dividing. This is the lag phase – They then grow and divide during the log or exponential phase – Eventually the culture runs out of metabolites and toxins build up . the bacteria stop growing and enter the stationary phase.
  • 66. GRAM –ve GRAM +ve Borellia – spirochete Streptomyces Bordatella – Rod Streptococcus – cocci in chains Campylobacter – curved rod Staphylococcus – cocci in clusters Treponema - spirochete Nocardia Vibrio – rod Listeria - rods Yersinia – rod Lactobacillus Chlamydia Gardnerella - rods Enterobacter Enterococcus Escherichia – Rods Corynebacteria Helicobacter – curved Rods Clostridium- spore forming Hemophillus - Rods Bacillus – rods, some spore forming Klebsiella – rods Actinomyces Legionella – rods Leptospira - spirochete EXCEPTIONS Nesseria – diplococcus Mycoplasma – No cell wall Pseudomonas - rod Mycobacteria – Acid fast bacilli Ricketssia Salmonella – rod Shigella – rod
  • 67. FUNGI Study of fungi is referred to as mycology – Fungi cause diseases in humans – They also contribute to food spoilage, are a major cause of plant disease and destroy timber, textiles and several synthetic materials – They play a role in the decay of plant and animal remains in the soil – Fungi are also beneficial to humans in that they are used in production of antibiotics, steroids, products of fermentation – alcohol, cheese, wine, bread making
  • 68. • They occupy many niches in the environment • They are free living and abundant in nature, only few exist as normal flora in humans • Fewer of them are associated with human disease • Fungi do not need to colonise or infect tissues of animals or man to perpetuate or preserve the species ( with the exception of candidiasis and tinea versicolor)
  • 69. Structure • Have a typical eukaryotic cell • They have a cell wall made of chitin • Some fungi have a polysaccharide capsule around the cell wall to isolate it from the environment. This helps in virulence if the fungi are pathogenic • Most fungi respire aerobically, others are strict anaerobes and others are facultative anaerobes • They have special staining to identify them
  • 70. • fungi are heterotrophic ( “other feeding,” must feed on preformed organic material), not autotrophic ( “self feeding,” make their own food by photosynthesis). • - Unlike animals (also heterotrophic), which ingest then digest, fungi digest then ingest: they produce exoenzymes to accomplish this • Most fungi store their food as glycogen (like animals). Plants store food as starch.
  • 71. • Fungal cell membranes have a unique sterol, ergosterol, which replaces cholesterol found in mammalian cell membranes • The body of fungi is termed thallus (nonreproductive) –The thalli of yeast are small, globular and are single celled –The thalli of mold are composed of long, branched tubular filaments called hyphae.
  • 72.
  • 73. classification • Fungi can be divided into 2 basic morphological forms: –Yeast – unicellular, reproduce asexually by budding or fission –Molds (Hyphae) – branching, thread like, tubular filaments.they elongate at their tips by a process called apical extension. A mass of hyphae forms a mycelium ( commonly known as mold)
  • 74. • The morphology of fungi is not fixed. Some can exist in hyphae or yeast form (dimorphic) depending on the environment (i.e in soil, decaying tissue or in host tissue) • Most pathogenic fungi are dimorphic fungi –At 37° C; yeast-like –At 25° C: mold-like –Can also occur with changes in CO2
  • 76. Most reproduce by budding
  • 77. examples • Candida albicans – part of the normal flora of mouth, GIT and vaginal wall • Malassezia furfur – causes skin infection • HIstoplasma capsulatum • Blastomyces dermatitidis • Coccidiodes immitis • Trichophyton and Microsporum sp. – cause ring worm • Cryptococcus neoformans – cryptococcal meningitis in ISS
  • 78.
  • 79. Human pathological fungi • The majority of most human pathogenic fungi appear to be soil inhabiting species where they live as saprobes • Given the appropriate conditions, i.e. if the person is not healthy, an open wound is present, direct injection of fungus into the system, a particular life-style, AIDS, etc., they will aggressively attack people
  • 80. Superficial infections/ cutaneous • Are caused by fungi that attack the skin or its appendages (nail, feathers and hair). • Some examples of these infection include ringworms, jock-itch(tinea cruris) and athlete's foot. • These fungi are known as dermatophytes
  • 81. Ringworm and Related Dermatophytes • Ringworm usually occurs on the exposed parts of the body, forming circular growths that may appear darker or lighter than the normal skin color, with symptoms that include skin lesion, rash and itching of the infected area • Caused by Trichophyton and Microsporum
  • 82. • They include; – Tinea capitis: Ringworm of the scalp, eyebrow and lashes. – Tinea corporis: Ringworm of the body. – Tinea cruris: Ringworm of the groin, perineum and perianal region. Infections are commonly referred to as "jock itch". – Tinea unguium: Ringworm of the nail. – Tinea barbae: Ringworm of the beard. – Tinea pedis: Ringworm of the feet. Infections are commonly referred to as athlete's foot. – Tinea manuum: Ringworm of the hand.
  • 83. Systemic or Deep-Seated Mycoses Coccidioides immitis • The cause of Coccidioidomycosis (Valley Fever) –Coccidioides immitis is contracted by inhalation of spores and primarily causes a respiratory disease in animals and people, but from the lungs it may spread throughout the body by way of the bloodstream
  • 84. • Histoplasma capsulatum and Histoplasmosis –Histoplasmosis occurs in people and dogs, rarely has it occurred in other domestic or wild animals. –Infection occurs through inhalation of spores from this fungus.
  • 85. • Blastomyces and Blastomycosis – There are two species of this genus, Blastomyces dermatitidis and B. brasiliensis Infection apparently comes from spores or mycelium in the soil and any part of the body may be invaded. – Infections usually are first detected as skin lesions; the lesions may remain localized or may gradually enlarge. In some case the fungus can spread throughout the whole body, resulting in extensive ulceration.
  • 86. Intermediate Infections (subcutaneous • These are diseases that are intermediate between the first two categories. • These fungal infections may extend to a considerable depth within the tissue, but unlike the systemic diseases will not be distributed to the rest of the body. • One of the most common intermediate infection is Candida albicans.
  • 87. Candida albicans and Candidiasis – Candida albicans is a dimorphic fungus. That is, it grows as both mycelium and yeasts.. – This fungus normally occurs in the mouth, digestive tract, and vagina of perfectly healthy people, but under some circumstances, and for reasons unknown, it may cause severe and even fatal infections, with lesions and eruptions of the skin, nails, mouth, bronchial tubes and lungs. – Oral infections known as thrush is relatively common..
  • 88. Aspergillus fumigatus and Aspergillosis – Aspergillus fumigatus sometimes parasitizes animals, especially birds, infecting mainly lungs and causing heavy mortality in birds. – In people, the disease can lead to a chronic lung infection which is apparently very contagious. The fungus is thought to cause death, but that is not certain. In patients that have died and A. fumigatus has been isolated, many have also had underlying disease that possibly lowered their resistance to the fungus.
  • 89. PARASITES Types of parasites according to living environment: • Ectoparasite: Living on the surface of other organisms lice, ticks, mites, etc. • Endoparasites: Live inside the body of other organism, e.g. Entamoeba histolytica, Ascaris lumbricoides, etc. • Obligate parasites: spend some part of their life cycle in or on host, e.g. plasmodium.
  • 90. • Facultative parasites: may be free living but can obtain the nutrition from hosts too. • Accidental parasites: when parasite attacks unnatural host. • Aberrant parasite: when the parasite comes to a site, during migration where it cannot live or develop further
  • 91. Types of host • Definitive host: when it harbors parasite in adult form or where parasite utilizes sexual method of reproduction). • Intermediate host: harbor’s larval stages of parasite). • Paratenic host: when host harbors parasite exhibiting no development but this parasite remains viable).
  • 92. • Reservoir host: which make parasites available for transmission to other hosts. • Natural host: which is naturally infected with certain species of parasite. • Accidental host: one who is not usually infected with parasite.
  • 93. The Effect of Parasites on their Host 1. Mechanical Injury: –Pressure created in tissues as it grows larger, e.g. hydatid cyst –Blockage of ducts such as • Blood vessels producing infarction, e.g. strongyloides • Lymphatic vessels to produce edema and elephantiasis, e.g. filariasis
  • 94. • The intestinal tract to produce obstruction, perforation and necrosis, e.g. Ascaris lumbricoides –Destruction of architecture of the human red blood cells by Plasmodium falciparum.
  • 95. 2. Producing toxic substances –Plasmodium falciparum, produce toxic substances may cause rigors and other symptoms characteristic of clinical malaria. –Entamoeba histolytica lesions in human gut may be due to the production of histolytic enzyme (tissue dissolving).
  • 96. 3. Deprivation of Nutrients, Fluids and Metabolites – Diphylobothrium latum (fish tapeworm) is known to deprive its host of vitamin B12 thus causing megaloblastic anemia. – Ancylostoma duodenale and some other blood sucking arthropod parasites quickly lead to severe iron deficiency anemia in patients infested by large numbers of these parasites
  • 97. 4. Introduction of Pathogenic Microorganisms – Bacterial infection of lesions produced initially by a parasite may occur and in some cases may prove lethal, e.g. tetanus is a well-known complication of Dracunculus medinensis infection. – This is the result of the spores of Clostridium tetani contaminating the ulcers of the foot and digit, produced by Dracunculus medinensis.
  • 98. Classification of parasites 1. According to their anatomical habitat in humans, they are classified into two groups a) ectoparasites (parasitizing the skin surface b) Endoparasites: parasitizing the internal tissues 2. According to their cellular structure, they are classified into two groups: a) Protozoa (each is unicellular b) Metazoa (multicellular)
  • 99. PROTOZOA According to the body systems they are classified into : a) Hemopoietic b) Intestinal c) Genitourinary d) Cutaneous e) Others
  • 100. 1. Hemopoietic protozoa: –Plasmodium species –Leishmania species –Trypanosoma species –Toxoplasma species
  • 101. 2. Intestinal protozoa: –Entamoeba histolytica –Blantidium coli –Giardia lamblia –Cryptosporidium parvum –Isospora belli 3. Genitourinary: Trichomonas vaginalis
  • 102. Metazoa • Classified into nematodes, helminthes • Helminthes are further classified into: 1. Cestodes 2. Nematodes 3. Trematodes
  • 103. Cestodes (tapeworms) 1. Taenia saginata and Taenia solium 2. Hymenolepis nana 3. Diphyllobothrium latum 4. Dipylidium caninum 5. Echinococcus granulosus 6. Echinococcus multolocularis
  • 104.
  • 105. Nematodes (roundworms) • Further classified into intestinal nematodes, tissue nematodes and trematodes • Ascaris lumbricoides • Hookworms • Enterobius vermicularis • Trichuris trichiura
  • 106. Trematodes (flukes) • Schistosoma masoni • Schistosoma haematobium • Schistosoma japonicum • Hermaphroditic flukes
  • 107. Adult Schistosoma (male and female)
  • 109. VIRUSES • Viruses are the smallest microorganism – smaller than bacteria. • The smallest viruses are about 0.02 μm (20 nanometers), while the large viruses measure about 0.3 μm (300 nanometers). Smallpox viruses are among the largest viruses; polio viruses are among the smallest.
  • 110. • Viruses are noncellular genetic elements that use a living cell for their replication and have an extracellular state. • Viruses are ultramicroscopic particles containing nucleic acid surrounded by protein, and in some cases, other components such as a membrane like envelope.
  • 111. • Viruses are obligate intracellular parasites – depend on the host cell for replication. • Viruses cannot make energy, proteins or replicate their genome outside the host cell. • The virus therefore must adapt to the biochemical nature of the host cell to use its systems. They therefore must be infectious to survive. • Outside the host cell, the virus particle is also known as a virion. The virion is metabolically inert and does not grow or carry on respiratory or biosynthetic functions.
  • 112. Classification of viruses • Viruses can be classified according to : – Structure – size, morphology – Genome – mode of replication – DNA or RNA – Disease they cause – Means of transmission e.g air, waterborne – Host cell – plants, animals and bacteria • For our level, viruses will be classified according to their genetic material or means of replication.
  • 113. DNA viruses RNAViruses Family Members Family Members Poxviridae Smallpox, Herpes simplex, Varicella zoster virus Cytomegalovirus paramyxoviridae measles virus mumps virus Adenoviridae Adenovirus Orthomyxoviridae Influenza virus
  • 114. Hepadnaviridae Hepatitis B virus Rhabdoviridae Rabies virus Papoviridae Human papilloma virus Filoviridae Ebola virus Marbug virus Retroviridae Human immunodeficiency virus (HIV) Human T cell leukemia virus DNA viruses RNAViruses
  • 115. DNA RNA Reoviridae Rotavirus Picornavirida e Polio virus Rhinoviruses Togaviridae Rubella virus Coronaviridae Corona Virus
  • 116. Viral Structure and Replication • Certain viruses contain ribonucleic acid (RNA), while other viruses have deoxyribonucleic acid (DNA). The nucleic acid portion of the viruses is known as the genome. • The nucleic acid may be single-stranded or double-stranded; it may be linear or a closed loop; it may be continuous or occur in segments.
  • 117. • The genome of the virus is surrounded by a protein coat known as a capsid, which is formed from a number of individual protein molecules called capsomeres. Capsomeres are arranged in a precise and highly repetitive pattern around the nucleic acid. The combination of genome and capsid is called the viral nucleocapsid.
  • 118. • A number of kinds of viruses contain envelopes. An envelope is a membrane like structure that encloses the nucleocapsid and is obtained from a host cell during the replication process. • The envelope contains viral-specified proteins that make it unique. Among the envelope viruses are those of herpes simplex, chickenpox, and infectious mononucleosis
  • 120. Viral replication • Attachment. , the virus adsorbs to a susceptible host cell using spikes. Cell surface receptors may exist on bacterial pili or flagella or on the host cell membrane. • Penetration of the virus or the viral genome into the cell. May occur by phagocytosis; or the envelope of the virus may blend with the cell membrane • Replication; – The protein capsid is stripped away from the genome, and the genome is freed in the cell cytoplasm where it either act as a messenger RNA (in RNA viruses)or synthesize messenger RNA from DNA (in DNA viruses)that provides codes for synthesis of enzymes
  • 121. • Viral protein synthesis – carried out on host cell ribosomes • Assembly - viral parts come together and enclose viral genome in a functional package • Release of new viral particles; NB; The replication process in which the host cell dies is called the lytic cycle of reproduction. The viruses so produced are free to infect and replicate in other host cells in the area.
  • 122.
  • 123.
  • 124. Lysogeny • Not all viruses multiply by the lytic cycle of reproduction. • Certain viruses remain active within their host cells for a long period without replicating. This cycle is called the lysogenic cycle. • The viruses are called temperate viruses, or proviruses, because they do not bring death to the host cell immediately. • The temperate virus exists in a latent form within the host cell and is usually integrated into the chromosome.
  • 125. • An example of lysogeny occurs in HIV infection. In this case, the human immunodeficiency virus remains latent within the host T-lymphocyte. An individual whose infection is at this stage will not experience the symptoms of AIDS until a later date
  • 126.
  • 129. Introduction • The word Immune if from latin word “immunus” meaning to be free • Immunity also refers to when people survive a calamity of epidemic diseases when faced with the same disease again • Immunology is the study of physiological mechanisms that humans and other animals use to defend their bodies from invading organisms e.g bacteria, viruses, fungi, parasites and toxins
  • 130. Definition of terms 1. Antigen: any molecule that binds to immunoglobulin or T cell receptor e.g. bacteria, fungi, viruses, cancer cells and toxins 2. Pathogen: Microorganisms that can cause disease 3. Antibody: a toxin or other foreign substance that induces an immune response; produced in response to a specific antigen 4. Immunoglobulin (Ig): antigen binding molecules of B cells 5. Vaccination: deliberate induction of protective immunity to a pathogen 6. Immunization: The ability to resist infection
  • 131. Cells of the immune system • White blood cells also called leukocytes are the cells of the immune system • All leukocytes are produced and derived from the hematopoietic stem cell in the bone marrow • They are found throughout the body; in blood lymphatic system and tissues
  • 132. • Types of leukocytes: –Monocytes –Granulocytes: neutrophils, basophils, eosinophils –Lymphocytes: B lymphocytes, T lymphocytes and natural killer cells
  • 133. Organs of the immune system The cells involved in the immune response are effectively organized into tissues and organs. The major lymphoid organs are classified into either primary or secondary organs • Primary lymphoid organs (thymus and bone marrow) are the major sites of lymphocyte development (lymphopoiesis). • Secondary lymphoid organs (spleen, lymph nodes, mucosal associated lymphoid tissue) provide the environment for the proliferation and maturation of cells involved in the adaptive immune response
  • 134.
  • 136. Ct. Lines of defense When a foreign antigen is introduced into an animal, the animal will respond immunologically to it using either of the two lines of defense. 1. Innate immunity (non specific)-first line of defense 2. Adaptive immunity or Acquired immunity (Specific)- second line of defense
  • 137. 1. Innate immunity (non specific)-first line of defense • It is an antigen-independent (non-specific) defense mechanism that is used by the host immediately or within hours of encountering an antigen. • It has no immunologic memory and, therefore, it is unable to recognize or “memorize” the same pathogen should the body be exposed to it in the future.
  • 138. Involves; 1. Barriers: –Skin (epidermis and dermis) –Mucous membranes: respiratory, GI, genitourinary tracts –Lacrimal apparatus; tears –Saliva
  • 139. 2. Chemical: –Sebum: acids –Perspiration; lysozyme –Gastric juice –Urine
  • 140. The skin • Serves both as mechanical and chemical barrier • Microorganisms normally associated with skin prevent potential pathogens from colonizing • Sebaceous glands secrete fatty acids and lactic acid which lower the skin PH (PH 4-6) • Unbroken skin is a contiguous barrier
  • 141. Mucosal membranes • Consist of epithelial layers and underlying connective tissue layer • Mucosal membranes of respiratory tract contains hair like projections called cilia that remove microbes inhaled through the nose and mouth • Mucus secreted by goblet cells prevent the microbes from associating too closely with the cells • Mucous membrane’s microbial activity owed due to presence of lysozyme, mucopeptide and secretory immunoglobulin A
  • 142. Lacrimal apparatus • Tear mechanically removes the foreign particles and also contains lysozyme which constantly baths surface of the eye. • Lysozyme breaks the peptidoglycan layer, causing bacteria to lyse
  • 143. Saliva • Saliva mechanically washes pathogens off teeth and reduces the number of pathogens • Saliva contains an antibody called secretory immunoglobulin which coats every tooth from harmful bacteria that may cause decay
  • 144. The major functions of the innate immune system include: 1. Acting as a physical and chemical barrier to infectious agents. 2. Recruiting immune cells to sites of infection, (such as phagocytes (macrophages and neutrophils), dendritic cells, mast cells, basophils, eosinophils, natural killer (NK) cells and lymphocytes) to sites of infection) through the production of chemical factors, including specialized chemical mediators, called cytokines/ chemokines (small proteins involved in cell-cell communication).
  • 145. • Cytokine production leads to the release of antibodies and other proteins and glycoproteins which activate the complement system 3. Activation of the complement cascade to identify bacteria, activate immune cells and to promote clearance of antibody complexes or dead cells
  • 146. 4. The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialized white blood cells 5. Activation of the adaptive immune system through a process known as antigen presentation
  • 147. Cells of innate immunity • Cells of innate immunity are majorly leukocytes (WBC) • Leukocytes are able to move freely and interact with and capture cellular debris, foreign particles, or invading microorganisms. • Unlike many other cells in the body, most innate immune leukocytes cannot divide or reproduce on their own, but are the products of multipotent hematopoietic stem cells present in the bone marrow
  • 148. The innate leukocytes include: • Natural killer cells • Mast cells • Eosinophils • Basophils • Phagocytic cells includes macrophages, neutrophils, and dendritic cells
  • 149. 1.Mast cells • These cells reside in connective tissue and in the mucous membranes. • They are intimately associated with wound healing and defense against pathogens, but are also often associated with allergy and anaphylaxis
  • 150. 2.Phagocytic cells • The word 'phagocyte' literally means 'eating cell'. • These are immune cells that engulf, i.e. phagocytose, pathogens or particles. (i.e., the particle is now inside the cell). Once inside the cell, The phagocytes releases lysosome that contains enzymes and acids that kill and digest the particle or organism
  • 151. • They are also able to react to a group of highly specialized molecular signals produced by other cells, called cytokines. • They include macrophages, neutrophils, and dendritic cells • Phagocytosis of the hosts’ own cells is common as part of regular tissue development and maintenance
  • 152. • When host cells die, either internally induced by processes involving programmed cell death (also called apoptosis) or caused by cell injury due to a bacterial or viral infection, phagocytic cells are responsible for their removal from the affected site. – This helps in growth and development of new healthy cells, phagocytosis is an important part of the healing process following tissue injury.
  • 153. a)Macrophages • Macrophages, from the Greek, meaning "large eaters," are large phagocytic leukocytes, which are able to move outside of the vascular system by moving across the walls of capillary vessels and entering tissues in pursuit of invading pathogens. • In tissues, organ-specific macrophages are differentiated from phagocytic cells present in the blood called monocytes.
  • 154. • Unlike neutrophils (which are short-lived cells), macrophages are long-lived cells that not only play a role in phagocytosis, but are also involved in antigen presentation to T cells. • Macrophages are named according to the tissue in which they reside. For example, –In blood - monocytes
  • 155. –In the liver are called Kupffer cells –In the connective tissue are termed histiocytes –Dust cells (within pulmonary alveolus), –Microglial cells (neural tissue), –Epithelioid cells (granulomas), –Osteoclasts (bone), –Mesangial cells (kidney)
  • 156. • Macrophages are the most efficient phagocytes, and can phagocytose substantial numbers of bacteria or other cells or microbes. • The binding of bacterial molecules to receptors on the surface of a macrophage triggers it to engulf and destroy the bacteria . • Pathogens also stimulate the macrophage to produce chemokines, which summons other cells to the site of infection
  • 157. b)Neutrophils • Neutrophils, along with two other cell types; eosinophils and basophils are known as: –Granulocytes due to the presence of granules in their cytoplasm, or as –Polymorphonuclear cells (PMNs) due to their distinctive lobed nuclei.
  • 158. • Neutrophils are the most abundant type of phagocyte, normally representing 50 to 60% of the total circulating leukocytes, and are usually the first cells to arrive at the site of an infection • In addition to their phagocytic properties, neutrophils contain granules that, when released, assist in the elimination of pathogenic microbes by killing or inhibiting growth of bacteria and fungi
  • 159. • The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times the number per day during acute inflammation.
  • 160. c)Dendritic cells • Dendritic cells are phagocytic cells present in tissues that are in contact with the external environment, mainly; –The skin (where they are often called Langerhans cells) –The inner mucosal lining of the nose, lungs, stomach, and intestines.
  • 161. • They resemble neuronal dendrites in shape but are not connected to the nervous system. • Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive immune systems
  • 162. 3.Basophils and eosinophils Basophils When activated by a pathogen encounter, basophils release histamine that plays a role in allergic reactions (such as asthma). • Unlike mast cells, which generally reside in the connective tissue surrounding blood vessels, basophils reside in the circulation. – Along with mast cells, basophils also control mechanisms associated with allergy and asthma.
  • 163. eosinophils • Play an important role in the destruction of parasites that are too large to be phagocytosed. • Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effective in killing bacteria and parasites, but are also responsible for tissue damage occurring during allergic reactions. • This process is tightly regulated to prevent any inappropriate tissue destruction.
  • 164. 4.Natural killer cells • Natural killer cells, or NK (also known as large granular lymphocytes (LGLs) cells, are a component of the innate immune system that does not directly attack invading microbes. • Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self."
  • 165. • This term describes cells with low levels of a cell- surface marker called MHC I (major histocompatibility complex) - a situation that can arise in viral infections of host cells. • NK cells play a major role in the rejection of tumours and the destruction of cells infected by viruses. • Destruction of infected cells is achieved through the release of perforins and granzymes from NK- cell granules which induce apoptosis (programmed cell death)
  • 166. • They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self.”
  • 167. 2.Adaptive immunity or Acquired immunity (Specific)- second line of defense • Is antigen-dependent and antigen-specific; • It has the capacity for memory, which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. This is its hallmark • It takes a longer time to build
  • 168. • Involves the T and B cells • Humoral immunity (mediated by B cells) and cell mediated immunity (mediated by T cells) • It has the ability to distinguish between self and non-self
  • 169. Second line of defense; • Phagocytosis • Inflammation • Complement • Interferon
  • 170. phagocytosis Process of phagocytosis involves: • Phagocytosis of enemy cell (antigen) • Fusion of lysosome and phagosome • Enzymes start to degrade enemy cell • Enemy cell broken into small fragments • Fragments of antigen presented on APC surface • Leftover fragments released by exocytosis
  • 171.
  • 172. Interferon (INF) • Interferon are proteins released by virus infected cells and which react with uninfected cells so as to render them resistant to infection by viruses • The name originates from the fact that they interfere with viral infection • Produced by fibroblast, macrophages, plasmacytoid cells
  • 173. • Are of three types, alpha, beta and gamma interferons: – ᾳ interferons are produced by B lymphocytes and Monocytes – β interferons are produced from fibroblasts and epithelial cells – ϒ interferons are produced by t cells
  • 174. Complement system Is a biochemical reaction of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or marks pathogens for destruction by other cells (phagocytes). The cascade is composed of many plasma proteins, synthesized in the liver
  • 175. Basic functions of the complement system – Opsonization – coats pathogens ‘tagging’ them for destruction and this enhances phagocytosis of the antigens – Chemotaxis – attracting macrophages and neutrophils (trigger recruitment of inflammatory cells) – Cell lysis – rupturing membranes of foreign cells – Agglutination – clustering and binding pathogens together – Clearing antigen/ antibody complexes and dead cells
  • 176. Inflammation • It is defined as a programmed local tissue response to local injury or tissue damage • Inflammation is one of the first protective responses to infection or irritation. • It is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens
  • 177. Signs of inflammation • Rubor (redness) • Tumor (swelling) • Calor (heat) • Dolor (pain) • Functiolaesa (loss of function) NB: the first four are referred to as the four cardinal signs
  • 178. Types of inflammation • Acute inflammation • Chronic inflammation • Chronic active inflammation
  • 179. • The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, (dendritic cells, histiocytes, Kupffer cells, and mastocytes). • At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation.
  • 180. • Chemical factors are produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause vasodilation of the blood vessels at the scene, and attract phagocytes, especially neutrophils.
  • 181. Type 1 hypersensitivity • Type 1 hypersensitivity reaction is commonly called allergic or immediate hypersensitivity reaction • Type 1 reaction is always rapid, occurring within minutes of exposure to an antigen, and always involves IgE-mediated degranulation of basophils or mast cells
  • 182. • Type 1 reactions are also known as IgE- mediated hypersensitivity reaction • IgE is responsible for sensitizing mast cells and providing recognition of antigen for immediate hypersensitivity reactions • Normaly occur in two forms: anaphylaxis and atopy
  • 183. Anaphylaxis: • acute potentially fatal and systemic manifestation of immediate hypersensitivity reaction • It occurs when an antigen (allergen) binds to IgE on the surface of mast cells with the consequent release of several mediators of anaphylaxis • Binding of IgE to the mast cells is also known as sensitization, because IgE –coated mast cells are ready to be activated on repeat antigen encounter
  • 184. • The initiater of type 1 reaction is otherwise known as an allergen • Examples or allergens: plant pollen, proteins, certain food items (eggs, milk, seafood), nuts, drugs (e.g. penicillin, sulphonamides, aspirin, local anesthetics, animal hair e.t.c.
  • 185. Mediators of anaphylaxis • Histamine • Slow reacting substances of anaphylaxis (SRS- A) i.e. leukotrienes • Serotonin • Eosinophilic Chemotactic Factors of Anaphylaxis • Prostaglandins and Thromboxanes
  • 186. histamine • It is the most important mediators of anaphylaxis • It is found in a preformed state in granules of mast cells and basophils • Causes vasodilatation, increased capillary permeability and smooth muscle contraction • It is the principal mediator of allergic rhinitis, urticaria, and angioedema
  • 187. Clinical manifestations of anaphylaxis • Anaphylaxis is an acute, life-threatening reaction usually affecting multiple organs • The time of onset of symptoms depends on the level of hypersensitivity and amount, diffusibility and site of exposure to the antigen Organs involved: • Skin: pruritus, flushing, urticarial, angioedema • Respiratory tract: bronchospasm and laryngeal edema • Cardiovascular system: hypotension an cardiac arrhythmias
  • 188. Atopy • Recurrent non-fatal and local manifestation of immediate hypersensitivity reaction • Localized to a specific tissue, often involving epithelial surfaces at the site of antigen entry • Mediated by IgE antibodies; atopic individuals produce high levels of IgE in response to allergens as against the normal individuals who do not • Common manifestations are: asthma, rhinitis, urticarial and atopic dermatitis
  • 189. Type II(cytotoxic) hypersensitivity • Mediated by antibodies directed against antigens on the cell membrane that activates complement thereby causing antibody mediated destruction of cells • The cell membrane is damaged by a membrane attack complex during activation of the complement • The reactions involve combination of IgG or IgM antibodies with the cell-fixed antigens or alternatively circulating antigens absorbed into cells
  • 190. • Antigen antibody reaction leads to complement activation resulting to formation of membrane attack complex • Antibody-dependent cell-mediated cytotoxicity (ADCC) is another mechanism which involves the binding of cytotoxic cells with Fc receptors in the Fc binding part of the antibodies coating the target cells
  • 191. • In type II reactions, the antigens may be blood platelets, red or white blood cells with drugs attached to their surface and the immune response may thus cause thrombocytopenia, hemolytic anemia or agranulocytosis
  • 192. Examples of type II • AB and Rh blood group reactions: Transfusion reactions Erythroblastosis fetalis (hemolytic disease of newborns • Autoimmune disease such as: Rheumatic fever where antibodies result in joint and heart valve damage Idiopathic thrombocytopenic purpura where antibodies result in the destruction of platelets • Transplant rejection • Drug induced hemolysis
  • 193. Innate Adaptive Definition Immediate protective response that does not require previous exposure to antigen Immune resp a specific ant Type of defense Nonspecific immune response; can be first line or second line of defense specific: Seco defense Differences between Innate and adaptive immunity
  • 194. nnate immunity Adaptive immunity ormal flora, physical arriers, chemical barriers, hagocytes, histamine, nflammation, fever, omplement proteins Humoral and cell mediated immunity hagocytes such as macrophages, neutrophils, atural killer cells, monocytes, mast cells and endritic cells Lymphocytes and antigen presenting cells hey don’t have memory ecause they don’t generate mmunological memory They have long term memory because they ge immunological memory
  • 195. Innate Adaptive Effectiveness Less effective than adaptive More effectiv Presence Present at birth Created in re foreign subst Response Rapid or quick response Slow respons Inheritance Inherited from parents and passed to offsprings Cannot be inh
  • 196. Innate immunity Adaptive im system involvement Alternative and lectin pathways Classical pathwa antigen Genetically determined, no prior exposure or antibody production Produced by prio antibody produc ion None Immediate and d hypersensitivity Microbes Microbes and no agents (antigens
  • 197. Passive and active immunity • Active immunity: Naturally acquired active immunity Artificially acquired active immunity • Passive immunity: Naturally acquired passive immunity Artificially acquired passive immunity
  • 198. Active immunity • Naturally acquired: –Infection after contact with pathogens • Artificially acquired: –Vaccine; dead or attenuated pathogens
  • 199. Passive immunity • Naturally acquired: Antibodies passed from mother to fetus via placenta, or infant in milk • Artificially acquired: Injection of immune serum (gamma globulin)
  • 200. Herd immunity • Also referred to as Herd effect, community immunity, population immunity or social immunity • Protection from disease in a group, due to a large enough proportion of the population having immunity to prevent the disease from spreading from person to person • It is the reduced probability of an individual becoming infected when part of a vaccinated population
  • 201. • Protection by herd immunity applies to vaccinated as well as unvaccinated individuals • The chance of becoming infected in a population decreases with increasing density of individuals being vaccinated • Individuals who are immune to a disease act as a barrier in the spread of disease
  • 202. Continuation of Adaptive Immunity Also Called Acquired or Specific Immunity
  • 203. Adaptive immunity • Usually awakened when innate immunity is ineffective in eliminating infectious agents and the infection is established Primary functions of adaptive immunity include: • The recognition of “non-self” antigens in the presence of “self” antigens • The generation of pathogen/ antigen-specific immunologic pathways that eliminate specific pathogens or pathogen infected cells • The development of an immunologic memory that can quickly eliminate a specific pathogen should subsequent infections occur
  • 204. The cells of the adaptive immune system • The cells of the adaptive immune system are: – T lymphocytes and – B lymphocytes. • They are a subset of leukocytes, derived from the same multipotent hematopoietic stem cells
  • 205. Congenital immunodeficiency diseases are often caused by blocks at different stages of lymphocyte maturation Development of B and T lymphocytes
  • 206. Classes of lymphocytes Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier
  • 207. • The peripheral lymphoid organs contain a mixture of B and T cells in at least three stages of differentiation: – Naive cells that have not matured, left the bone marrow or thymus, have entered the lymphatic system, but that have yet to encounter their specific antigen, – Effector cells that have been activated by their specific antigen and are actively involved in eliminating a pathogen. – Memory cells – the long-lived survivors of past infections.
  • 208. Adaptive cont’ • B lymphocytes – are involved in ‘humoral’ or ‘antibody mediated’ immunity • T lymphocytes – are involved in ‘cell mediated’ immunity
  • 209. Different types of immune responses are mediated by different classes of lymphocytes and defend against different types of microbes Types of adaptive immunity
  • 210. Cell-mediated immunity does not involve antibodies, but rather protects an organism through : – The activation of antigen-specific cytotoxic T cells that induce cell death – The activation of macrophages and NK cells – The stimulation of cytokine production Cell-mediated immunity is directed primarily at microbes that survive in host cells. This type of immunity is most effective in eliminating virus- infected cells, but can also participate in defending against fungi, protozoa, cancers, and intracellular bacteria.
  • 211. Phases of adaptive immune responses
  • 213. T Lymphocytes and Antigen Presenting Cells (APCs) • T cells derive from hematopoietic stem cells in bone marrow and migrate to mature in the thymus. • These cells express a unique antigen-binding receptor on their membrane, known as the T- cell receptor (TCR) • They require the action of APCs (usually dendritic cells, macrophages, B cells and epithelial cells) to recognize a specific antigen.
  • 214. APCs • APCs include Dendritic cells, B-cells and macrophages They are equipped with special chemicals recognized by T Cell receptors on T lymphocytes Antigen presentation stimulates T cells to become either • “T - cytotoxic“ or CD8+ cells • “T - helper" or CD4+ cells. • T regulatory cells
  • 215. Exogenous antigen presentation • Dendritic cells engulf exogenous pathogens, such as bacteria or toxins in the tissues and then migrate to the T cell-enriched lymph nodes. • During migration, dendritic cells develop an ability to communicate with T-cells. • The dendritic cell uses enzymes to chop the pathogen into antigen pieces. In the lymph node, the dendritic cell will display these "non-self" antigens on its surface by coupling them to a "self"-receptor called the major histocompatibility complex (MHC) (also known in humans as Human leukocyte antigen (HLA)). • This MHC: antigen complex is recognized by T-cells passing through the lymph node which activate CD4+ helper T-cells.
  • 216. Endogenous antigen presentation • Endogenous antigens are produced by intracellular bacteria and viruses replicating within a host cell. • The host cell uses enzymes to digest virally associated proteins, and displays these pieces on its surface to T-cells by coupling them to MHC. • Endogenous antigens are typically displayed on MHC molecules and activate CD8+ cytotoxic T-cells.
  • 217. T Lymphocytes • CD8 or T cytotoxic lymphocytes • CD4 or T Helper lymphocytes • Regulatory T cells (T suppressor cells)
  • 218. CD8+ T lymphocytes or cytotoxic T lymphocytes • Cytotoxic T cells (also known as CD8, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a sub- group of T cells that induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional cells – Naive T cells are activated when their T-cell receptor (TCR) strongly interacts with MHC – antigen complex on APCs and is what keeps the CTL and infected cell bound together. – Once activated, the CTL gains functionality, and divides rapidly, to produce an army of “armed”-effector cells. Activated CTL will then travel throughout the body in search of cells bearing that unique MHC + antigen complex
  • 219. • When exposed to these infected or dysfunctional host cells, effector CTL release perforin and granulysin: cytotoxins that form pores in the target cell's plasma membrane and causing it to burst or lyse. • CTL also releases granzyme that enters cells via pores to induce apoptosis (cell death). – To limit extensive tissue damage during an infection, CTL activation is tightly controlled and in general requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T-cells
  • 220. • Upon resolution of the infection, most of the effector cells will die and be cleared away by phagocytes, but a few of these cells will be retained as memory cells. • Upon a later encounter with the same antigen, these memory cells quickly differentiate into effector cells, dramatically shortening the time required to mount an effective response
  • 221. Helper T-cells/ CD4+ • Are immune response mediators that play an important role in establishing and maximizing the capabilities of the acquired immune response • These cells have no cytotoxic or phagocytic activity; and cannot kill infected cells or clear pathogens, but, in essence "manage" the immune response, by directing other cells to perform these tasks.
  • 222. • Helper T cells express T cell receptors (TCR) that recognize antigen bound to I MHC molecules. • The activation of a naive helper T-cell causes it to release cytokines, which influences the activity of many cell types, including the APC (Antigen-Presenting Cell) that activated it. • Helper T-cells require a much milder activation stimulus than cytotoxic T cells. • They can provide extra signals that "help" activate cytotoxic cells.
  • 223. Types of CD4+ T helper cells responses Two types of effector CD4+ T helper cell responses can be induced by a professional APCs, • T helper 1 ( Th1) and • T helper 2 (Th2) Each designed to eliminate different types of pathogens
  • 224. • The Th1 response –Is characterized by the production of mediators (interferons) which activates the bacteriacidal activities of macrophages, and induces B cells to make opsonizing (coating) and complement- system antibodies, and leads to "cell-mediated immunity”. • The Th2 response –Is characterized by the release of Mediators (interleukins), which results in the activation of B cells to make neutralizing antibodies, leading to "humoral immunity” or “antibody mediated immunity”
  • 225. • ]In general, Th1 responses are more effective against intracellular pathogens (viruses and bacteria that are inside host cells), whereas Th2 responses are more effective against extracellular bacteria, parasites including helminths and toxins. • Like cytotoxic T cells, most of the CD4+ helper cells will die upon resolution of infection, with a few remaining as CD4+ memory cells
  • 226.
  • 227. What is unique about HIV? .
  • 228. HIV • HIV is able to weaken the immune system by attacking the CD4+ T cells, precisely the cells that could drive the destruction of the virus, • CD4 are also the cells that drive immunity against all other pathogens encountered during an organism's lifetime.
  • 229. Regulatory T cells (T-reg)/ suppressor cells • Limits and suppresses the immune system, and may control abnormal immune responses to self-antigens; an important mechanism in controlling the development of autoimmune diseases.
  • 230.
  • 231. conclusion T cells contribute to immune defenses in two major ways: • Some direct and regulate immune responses – T helper or CD4 cells • Others directly attack infected or cancerous cells – T cytotoxic or CD8 cells
  • 233. • B cells arise from hematopoietic stem cells in the bone marrow, mature and leave the marrow expressing a unique antigen-binding receptor on their membrane. • Unlike T cells, B cells can recognize free antigen directly, without the need for APCs. The principal function of B cells is the production of antibodies against foreign antigens.
  • 234. B lymphocytes and antibody production • B Cells are the major cells involved in the creation of antibodies that circulate in blood plasma and lymph, known as humoral immunity. • Antibodies (also known as immunoglobulin, Ig), are large Y-shaped proteins used by the immune system to identify and neutralize foreign objects • In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM, differing in biological properties
  • 235. B cell continued • Upon activation, B cells produce antibodies, each of which recognizing a unique antigen, and neutralizing specific pathogens. • Like the T cell, B cells express a unique B cell receptor (BCR). • All the BCR of any one type of B cells recognizes and binds to only one particular antigen. • A critical difference between B cells and T cells is that whereas T cells recognize their cognate antigen in a processed form coupled to the MHC molecule, B cells recognize antigens in their native/ original form
  • 236. • Once a B cell encounters its cognate (or specific) antigen (and receives additional signals from a helper T cell (esp Th2 type), it undergoes proliferation and differentiate into effector cells called: – Antibody-secreting plasma cells – Memory B cells
  • 237. Phases of lymphocyte activation Proliferation keeps pace with replicating microbes (e.g. 1 B cell --> 4,000 Ab-secreting cells --> ~1012 antibody molecules/hour) Differentiation: converts lymphocytes into effective defenders
  • 238. Antibody Secreting Plasma Cells • Plasma cells are short-lived cells (2–3 days) that secrete antibodies. These antibodies bind to antigens, making them easier targets for phagocytes, and trigger the complement system. • Plasma cells do not have antigen-binding receptors. These are short-lived cells that undergo apoptosis when the inciting antigen that induced the immune response is eliminated.
  • 239. • The secreted antibodies bind to antigens on the surface of pathogens, flagging them for destruction through pathogen and toxin neutralization, complement activation, opsonin promotion of phagocytosis and pathogen elimination. • Upon elimination of the pathogen, the antigen- antibody complexes are cleared by the complement system.
  • 240. Five types of antibodies are produced by B cells: • Immunoglobulin A (IgA) • Immunoglobulin D (IgD) • Immunoglobulin E (IgE) • Immunoglobulin G (IgG) and • Immunoglobulin M (IgM). Each of these antibodies has differing biological functions and recognize and neutralize specific pathogens.
  • 241. • Antibodies play an important role in containing virus proliferation during acute phase when viruses are still in circulation. However, they are not generally capable of eliminating a virus once viruses infect cells. • Once an infection is established, cell-mediated immune mechanisms are most important in host defense. B cells act as APC to T cells • About 10% of plasma cells will survive to become long-lived antigen-specific memory B cells
  • 242. Memory B cells • Memory B cells are “long-lived” survivors of past infection and continue to express antigen-binding receptors. • These cells can be called upon to respond quickly and eliminate an antigen upon re- exposure while the host experiences few, if any, symptoms
  • 243. Primary and secondary immune responses illustrate specificity and memory in adaptive immunity
  • 245. • The terms antibody/ immunoglobulin are found in the blood and tissue fluids, as well as many secretions. • In structure, they are large Y-shaped globular proteins. • There are five types of antibody: IgA, IgD, IgE, IgG, and IgM. Each differs in its biological properties and deals with different antigens. • Antibodies are synthesized and secreted by plasma cells that are derived from the B cells of the immune system.
  • 246. Antibodies contribute to immunity in three ways: –They prevent pathogens from entering or damaging cells by binding to them; –They stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and –They trigger destruction of pathogens by stimulating other immune responses such as the complement pathway
  • 247. • Each antibody recognizes a specific antigen unique to its target. • By binding their specific antigens, –Antibodies can cause agglutination and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, –Block viral receptors, –Stimulate other immune responses, such as the complement pathway.
  • 248. Example of antibody – antigen reaction • An incompatible blood transfusion causes a transfusion reaction, which is mediated by the humoral immune response. This type of reaction, called an acute hemolytic reaction, results in the rapid destruction (hemolysis) of the donor RBCs by host antibodies. The symptoms are fever and chills, back pain and pink or red urine (hemoglobinuria). The major complication is that hemoglobin released by the destruction of RBCs can cause acute renal failure
  • 249. Antibodies IgA • Found in secretions in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens. Also found in saliva, tears, and breast milk. IgD • It has been shown to activate basophils and mast cells to produce antimicrobial factors.
  • 250. IgE • Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in allergy. • Also protects against parasitic worms IgG • Provides the majority of antibody-based immunity against invading pathogens. Most abundant antibody (70-80% of all Ig). • The only antibody capable of crossing the placenta to give passive immunity to the fetus IgM • Found on the surface of B cells and in circulation. • Eliminates pathogens in the early stages of B cell- mediated (humoral) immunity before there is sufficient IgG.
  • 251. • Humans also produce "natural antibodies" that are present in serum before microbial infection. • Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination, other foreign antigen exposure or passive immunization. – These antibodies can activate the classical complement system leading to lysis of enveloped bacteria and viruses particles long before the adaptive immune response is activated
  • 252. Antibody-mediated (Humoral) vs. cell- mediated immunity • Humoral immunity – Immunity provided through antibodies • Cell mediated immunity does not involve antibodies, but works through: –Activation of Ag-specific cytotoxic T cells –Activation of macrophages and NK cells, to destroy intracellular pathogens - The stimulation of cytokine production • Cell-mediated immunity is most effective in eliminating virus-infected cells, but can also participate in defending against fungi, protozoa, cancers, and intracellular bacteria. It plays a big role in transplant rejection
  • 253.
  • 254. Passive vs. Active immunization • Acquired immunity is attained through either passive or active immunization Passive immunization refers to the transfer of active humoral immunity, in the form of “ready-made” antibodies, from one individual to another. • It can occur naturally by transplacental transfer of maternal antibodies to the developing fetus, or • It can be induced artificially by injecting a recipient with exogenous antibodies targeted to a specific pathogen or toxin. – This is used when there is a high risk of infection and insufficient time for the body to develop its own immune response
  • 255. • Active immunization refers to the production of antibodies against a specific agent after exposure to the antigen. • It can be acquired through either – Natural infection with a microbe or – Through administration of a vaccine that can consist of attenuated (weakened) pathogens or inactivated organisms,
  • 256. Active and passive immunity Active immunity: long-lasting protection (memory), multiple effector mechanisms activated, lag time Passive immunity: rapid protection, short duration Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011
  • 257. Immunopathology Defects or malfunctions in either the innate or adaptive immune response can provoke illness or disease. Such disorders are generally caused by: • An overactive immune response (known as hypersensitivity reactions) • An inappropriate reaction to self (known as autoimmunity) • Ineffective immune responses (known as immunodeficiency).
  • 258. Hypersensitivity reactions Hypersensitivity reactions refer to undesirable responses produced by the normal immune system. There are four types of hypersensitivity reactions • Type I: immediate hypersensitivity • Type II: cytotoxic or antibody-dependent hypersensitivity • Type III: immune complex disease • Type IV: delayed-type hypersensitivity
  • 259. Type I - immediate hypersensitivity (anaphylaxis) – Antibodies (igE)bind to certain cells, causing re- lease of chemical substances that produce an inflammatory reaction. E.g Extrinsic asthma,Hay fever Type II - Cytotoxic or antibody dependent rx – Antibodies cause activation of complement system, which leads to tissue damage. Examples Transfusion reaction, ABO incompatibility, Hemolytic disease of the newborn
  • 260. Type III - Immune-complex reactions – Immune complexes are deposited in tissues, where they activate complement which results in a generalized inflammatory reaction. Examples Acute glomerulonephritis, Serum sickness Type IV - Delayed reactions – Antigens stimulate T cells that release lymphokines, which cause inflammation and tissue damage. Examples Contact dermatitis, Tuberculin skin test, Graft-versus- host disease, Allograft rejection
  • 261. Autoimmunity • Autoimmunity involves the loss of normal immune homeostasis such that the organism produces an abnormal response to its own tissue. • The hallmark of autoimmunity is the presence of self- reactive T cells, auto-antibodies, and inflammation. • Prominent examples of autoimmune diseases include: – Celiac disease – Small intestines – Type 1 diabetes mellitus – Islets of Langerhan – Addison’s disease – Adrenal gland – Graves’ disease – Thyroid gland
  • 262. Immunodeficiency • Refers to a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. • Immunodeficiency disorders may result from a primary congenital defect (primary immunodeficiency) or may be acquired from a secondary cause (secondary immunodeficiency), such as viral or bacterial infections, malnutrition or treatment with drugs that induce immunosuppression.
  • 263. • Certain diseases can also directly or indirectly impair the immune system such as leukemia and multiple myeloma. • Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). • HIV directly infects Th cells and also impairs other immune system responses indirectly.