3. 3
Helper T Lymphocytes
B Lymphocytes Antibodies
Cell-mediated Immunity
Humoral Immunity
Cytotoxic T Lymphocytes
Interleukins
Direct killing
of Microbes
4. ACTIVATION OF B LYMPHOCYTES
On entry of a foreign antigen, macrophages in the
lymphoid tissue phagocytize the antigen and then
present it to adjacent B lymphocytes
In addition, the antigen is presented to T cells at the
same time, and activated helper T cells are formed.
These helper cells also contribute to extreme
activation of the B lymphocytes
6. An antigen is a substance that evokes the
production of one or more antibodies
An immunogen is a specific type of antigen. An
immunogen is a substance that is able to provoke
an adaptive immune response if injected on its own
7. ANTIGENICITY
Foreignness
Size
The larger the molecule the more immunogenic it is
Chemical Composition
In general, the more complex the substance is chemically the
more immunogenic it will be
Physical form
In general particulate antigens are more immunogenic than
soluble ones
Degradability
Antigens that are easily phagocytosed are generally more
immunogenic. This is because for most antigens the development
of an immune response requires that the antigen be
phagocytosed, processed and presented to helper T cells by an
antigen presenting cell (APC)
8. ANTIGENICITY
Host Factors:
Genetic Factors
Some substances are immunogenic in one species but
not in another. Similarly, some substances are
immunogenic in one individual but not in others (i.e.
responders and non-responders)
Age
Age can also influence immunogenicity. Usually the very
young and the very old have a diminished ability to
mount and immune response in response to an
immunogen
9. HAPTENS
Haptens are small molecules which could never
induce an immune response when administered by
themselves but which can when coupled to a carrier
molecule
Free haptens, however, can react with products of
the immune response after such products have
been elicited
Haptens have the property of antigenicity but not
immunogenicity
10. SUPERANTIGENS
When the immune system encounters a
conventional T-dependent antigen, only a small
fraction of the T cell population is able to recognize
the antigen and become activated
However, there are some antigens which
polyclonaly activate a large fraction of the T cells
(up to 25%). These antigens are called
superantigens…
Examples of superantigens include: Staphylococcal
enterotoxins (food poisoning), Staphylococcal toxic
shock toxin (toxic shock syndrome) and Streptococcal
pyrogenic exotoxins (shock)
12. FORMATION OF ANTIBODIES
B lymphocytes specific for the antigen immediately
enlarge and take on the appearance of
lymphoblasts
Lymphoblasts further differentiate to form
plasmablasts, which are precursors of plasma cells
The mature plasma cell then produces gamma
globulin antibodies at an extremely rapid rate-about
2000 molecules per second
This process continues for several days or weeks
until finally exhaustion and death of the plasma
cells occur
13. MEMORY CELLS
A few of the lymphoblasts formed by activation of a
clone of B lymphocytes do not go on to form
plasma cells but instead form moderate numbers of
new B lymphocytes similar to those of the original
clone
These lymphocytes are called memory cells
Subsequent exposure to the same antigen will
cause a much more rapid and much more potent
antibody response this second time around
14.
15. PRIMARY RESPONSE AND SECONDARY RESPONSE
There is usually a 1-week delay in the appearance
of the primary response, its weak potency, and its
short life
The secondary response, by contrast, begins
rapidly after exposure to the antigen, is far more
potent, and forms antibodies for many months…
16. PRIMARY RESPONSE AND SECONDARY RESPONSE
The increased potency and duration of the
secondary response explain why immunization is
usually accomplished by injecting antigen in
multiple doses with periods of several weeks or
several months between injections
17. WHAT ARE ANTIBODIES
The antibodies are gamma globulins called
immunoglobulins (Ig), and they have molecular
weights between 160,000 and 970,000
All the immunoglobulins are composed of
combinations of light and heavy polypeptide chains
Most are a combination of two light and two heavy
chains
However, some of the immunoglobulins have
combinations of as many as 10 heavy and 10 light
chains
18.
19. STRUCTURE OF ANTIBODIES
A designated end of each light and heavy chain,
called the variable portion; the remainder of each
chain is called the constant portion
The variable portion is different for each specificity
of antibody, and it is this portion that attaches
specifically to a particular type of antigen
The constant portion of the antibody determines
other properties of the antibody
such as diffusivity of the antibody in the tissues and
other biological properties of the antibody
20. SPECIFICITY OF ANTIBODIES
Each antibody is specific for a particular antigen;
this is caused by its unique structural organization
of amino acids in the variable portions of both the
light and heavy chains
On a bivalent antibody, there are two variable sites
for attachment of antigens
A small proportion of the antibodies, which consist
of combinations of up to 10 light and 10 heavy
chains, have as many as 10 binding sites
21. TYPES OF ANTIBODIES
There are five general classes of antibodies,
respectively named IgM, IgG, IgA, IgD, and IgE
IgG, a bivalent antibody, constitutes about 75
percent of the antibodies of the normal person
The IgM class is also interesting because a
large share of the antibodies formed during the
primary response are of this type. These
antibodies have 10 binding sites that make
them exceedingly effective in protecting the
body against invaders
23. ANTIGEN ANTIBODY INTERACTIONS
Lock and Key Concept- The combining site of an
antibody is located in the Fab portion of the
molecule and is constructed from the hypervariable
regions of the heavy and light chains
Non-covalent Bonds- The bonds that hold the
antigen to the antibody combining site are all non-
covalent in nature. These include hydrogen bonds,
electrostatic bonds, Van der Waals forces and
hydrophobic bonds
Since antigen-antibody reactions occur via non-
covalent bonds, they are by their nature reversible
24. AFFINITY AND AVIDITY
Affinity- is the strength of the reaction between a single
antigenic determinant and a single combining site on the
antibody
Affinity is the equilibrium constant that describes the
antigen-antibody reaction. Most antibodies have a high
affinity for their antigens
Avidity- is a measure of the overall strength of binding of
an antigen with many antigenic determinants and
multivalent antibodies
Affinity refers to the strength of binding between a single
antigenic determinant and an individual antibody
combining site whereas avidity refers to the overall
strength of binding between multivalent antigens and
antibodies
25. SPECIFICITY AND CROSS REACTIVITY
Specificity- refers to the ability of an individual antibody
combining site to react with only one antigenic
determinant. In general, there is a high degree of
specificity in antigen-antibody reactions. Antibodies can
distinguish differences in:
The primary structure of an antigen
Isomeric forms of an antigen
Secondary and tertiary structure of an antigen
Cross reactivity- Cross reactivity refers to the ability of
an individual antibody combining site to react with more
than one antigenic determinant
Cross reactions arise because the cross reacting
antigen shares an epitope in common with the
immunizing antigen
27. TESTS FOR ANTIGEN-ANTIBODY REACTIONS
Some examples…
Blood typing…..
Qualitative Agglutination Test
Bacterial Infections…..
Quantitative Agglutination Test
Detection of Rh antibodies…..
Coomb’s Test
Qualitative analysis of complex mixtures of antigens…..
Immunoelectrophoresis
Quantitative analysis of Antigens/ Antibodies…..
ELISA
Detection of cell-associated antigens…..
Immunofluorescence, Flow Cytometry
28. HOW DO ANTIBODIES WORK?
Antibodies act mainly in two ways to protect the
body against invading agents:
(1) by direct attack on the invader (Antigen-
Antibody Interaction), and
(2) by activation of the "complement system" that
then has multiple means of its own for destroying
the invader
29. DIRECT ACTION OF ANTIBODIES ON INVADING
AGENTS
Agglutination: multiple large particles with antigens on
their surfaces, such as bacteria or red cells, are bound
together into a clump
Precipitation: the molecular complex of soluble antigen
and antibody becomes so large that it is rendered
insoluble and precipitates
Neutralization: the antibodies cover the toxic sites of the
antigenic agent
Lysis: some potent antibodies attack membranes of
cellular agents and cause their rupture
30.
31. COMPLEMENT SYSTEM FOR ANTIBODY ACTION
"Complement" is a collective term that describes a
system of about 20 proteins, many of which are enzyme
precursors
All these are present normally in the blood
When an antibody binds with an antigen, a specific
reactive site on the "constant" portion of the antibody
becomes "activated," and this in turn binds directly with
the C1 molecule of the complement system…
32.
33. COMPLIMENT CASCADE
Activation of C1 molecule of the complement
system, sets into motion a "cascade" of sequential
reactions
There is successively increasing quantities of
enzymes in the complement cascade
Multiple end products are formed, and several of
these cause important effects that help to prevent
damage to the body's tissues caused by the
invading organism or toxin…
34. FUNCTIONS OF COMPLEMENT
Opsonization and phagocytosis: One of the
products of the complement cascade, C3b, strongly
activates phagocytosis by both neutrophils and
macrophages
Lysis: One of the most important of all the products
of the complement cascade is the lytic complex,
C5b6789. This has a direct effect of rupturing the
cell membranes of bacteria or other invading
organisms
Agglutination: The complement products also
change the surfaces of the invading organisms,
causing them to adhere to one another, thus
promoting agglutination
35. FUNCTIONS OF COMPLEMENT
Neutralization of viruses: The complement enzymes
and other complement products can attack the
structures of some viruses
Chemotaxis: Fragment C5a initiates chemotaxis of
neutrophils and macrophages, thus causing large
numbers of these phagocytes to migrate into the
tissue area adjacent to the antigenic agent
Activation of mast cells and basophils: Fragments
C3a, C4a, and C5a activate mast cells and
basophils, causing them to release histamine,
heparin, and several other substances into the local
fluids. This causes local Inflammatory effects
37. IMMUNIZATION BY INJECTION OF ANTIGENS
Immunization has been used for many years to
produce acquired immunity against specific
diseases
A person can be immunized by
Injecting dead organisms that are no longer capable of
causing disease but that still have some of their
chemical antigens
Immunity can be achieved against toxins that have been
treated with chemicals so that their toxic nature has
been destroyed even though their antigens for causing
immunity are still intact
And, finally, a person can be immunized by being
infected with live organisms that have been "attenuated"
38. PASSIVE IMMUNITY
Temporary immunity can be achieved in a person
by infusing antibodies obtained from the blood of
someone else or from some other animal that has
been actively immunized against the antigen
Antibodies last in the body of the recipient for 2 to 3
weeks, and during that time, the person is protected
against the invading disease
39. SOME DRUGS MAY ACT AS HAPTENS !!
Hydralazine, a blood pressure-lowering drug
occasionally can produce drug-induced lupus
erythematosus in certain individuals
The anaesthetic gas halothane can cause a life-
threatening hepatitis
Some penicillin-class drugs may cause
autoimmune hemolytic anemia
40. REFERENCES
Guyton and Hall Textbook of Medical Physiology, 12th
edition, 2011
Naish Medical Sciences, 1st edition, 2011