2. INNATE
IMMUNITY
• Recall: always present;
ready to recognize and
eliminate microbes
(natural or native
immunity)
• powerful early defense
mechanism capable of
controlling and
eradicating infections
Tuesday, July 3, 2012
3. HOW IT DIFFERS FROM ADAPTIVE
IMMUNITY
Tuesday, July 3, 2012
4. How do INNATE immunity
recognize microbes?
• The components of
innate
immunity
recognize
structures that are shared by various classes of
microbes and are not present on host cells
• e.g. phagocytes express receptors for bacterial
lipopolysaccharide (LPS,also called endotoxin), which is
present in many bacterial species but is not produced by
mammalian cells
• The receptors of the innate immune system are
encoded in the germline and are not produced by
somatic recombination of genes
• e.g. germline-encoded pattern recognition receptors
have evolved as a protective adaptation to potentially
harmful microbe
Tuesday, July 3, 2012
5. How do INNATE immunity
recognize microbes?
• The innate immune system responds in the
same way to repeat encounters with a microbe
(no memory)
• The innate immune system does not react
against the host
• rationale #1: because of the inherent
specificity of innate immunity for microbial
structures
• rationale #2: partly because mammalian cells
express regulatory molecules that prevent
innate immune reactions
Tuesday, July 3, 2012
6. COMPONENTS OF THE
INNATE IMMUNITY
• The innate immune system
consist of epithelia which provide
barriers to infection, cells in the
circulation and tissues, and
several plasma proteins
• These components play different
but complementary roles in
blocking the entry of microbes
and in eliminating microbes that
enter the tissues of the host
Tuesday, July 3, 2012
7. EPITHELIAL BARRIERS
• The common
portals entry of
microbes: skin,
gastrointestinal
tract and
respiratory tract
• They are
protected by
continuous
epithelia that
provide physical
and chemical
barriers against
infections
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10. PHAGOCYTES
• The two types of circulating phagocytes:
neutrophils and monocytes
• they are recruited to the sites of
infection where they recognize and ingest
microbes for intracellular killing
Tuesday, July 3, 2012
12. 1. Neutrophils: Phagocytic
2. Basophils: Produce histamine
3. Eosinophils: Toxic to
parasites and some
phagocytosis
4. Dendritic cells: Initiate
adaptive immune response
5. Monocytes: Phagocytic as
mature macrophages
a. Fixed macrophages in lungs,
liver, and bronchi
b. Wandering macrophages
roam tissues
6. Lymphocytes: Involved in
specific immunity
Tuesday, July 3, 2012
14. NEUTROPHILS
• also called polymorphonuclear leukocytes (PMNs)
• most abundant leukocytes in blood (4,000-10,000/mm)
• during infections productions increases rapidly (up to
20,000/mm)
• production is stimulated by cytokines (colony-
stimulating factors/CSFs)
• first cell type to respond to most infections (bacterial
and fungal)
• ingest microbes in the circulation, and they rapidly enter
extravascular tissues at sites of infection where they
also ingest microbes and die after a few hours
Tuesday, July 3, 2012
15. MONOCYTES
• Less abundant than neutrophils (500-1,000/
mm)
• ingest microbes in the blood and in tissues
• monocytes that enter extravascular tissues
survive in these sites for long periods = in
the tissues, these monocytes differentiate
into cells called macrophages
Tuesday, July 3, 2012
22. NATURAL KILLER (NK) CELLS
• class of lymphocytes that respond
to intracellular microbes by killing
infected cells and by producing the
macrophage activating cytokine
IFN-a
• comprise about 10% of the
lymphocytes in the blood and
peripheral lymphoid organs
• recognize host cells that have been
altered by microbial infections
• NK cells and macrophages function
cooperatively to eliminate
intracellular microbes:
macrophages ingest microbes and
produce1L-12 = IL12 activates NK
cells to secrete IFN-g = IFN-g in
turn activates the macrophages to
kill the ingested microbes
Tuesday, July 3, 2012
24. THE COMPLEMENT
SYSTEM
• a collection of circulating and membrane-associated proteins that are
important in defense against microbes
• 3 pathways : alternative, classical and lectin
• ALTERNATIVE: triggered when some complement proteins are activated
on microbial surfaces and cannot be controlled because complement
regulatory proteins are not present on microbes (but are present on host
cells). = INNATE
• CLASSICAL: triggered after antibodies bind to microbes or other antigens
and is thus a component of the humoral arm of adaptive immunity
• LECTIN: activated when a plasma protein, mannose-binding lectin, binds to
terminal mannose residues on the surface glycoproteins of microbes = lectin
activates proteins of the classical pathway, but because it is initiated in the
absence of antibody it is a component of innate immunity
Tuesday, July 3, 2012
27. IMPORTANT
FUNCTIONS
• C3b coats microbes and promotes the binding of these
microbes to phagocytes, by virtue of receptors for C3b
that are expressed on the phagocytes
• Some breakdown products of complement proteins are
chemoattractants for neutrophils and monocytes and
promote inflammation at the site of complement
activation
• Complement activation culminates in the formation of a
polymeric protein complex that inserts into the microbial
cell membrane, forming pores that lead to the influx of
water and ions and death of the microbe
Tuesday, July 3, 2012
29. CYTOKINES OF THE
INNATE IMMUNITY
• In response to microbes, macrophages and other cells secrete proteins
called cytokines that mediate many of the cellular reactions of innate
immunity
• Macrophages responding to microbes produce cytokines that stimulate
inflammation (leukocyte recruitment) and activate NK cells to produce
the macrophage-activating cytokine IFN-g
Tuesday, July 3, 2012
32. PLASMA PROTEINS OF
THE INNATE IMMUNITY
• Plasma mannose-binding lectin (MBL): recognizes
microbial carbohydrates and can coat microbes for phagocytosis or
activate the complement cascade by the lectin pathway.
• belongs to the collectin family of proteins, which share
homology to collagen and contain a carbohydrate-binding
(lectin) domain
• Surfactant proteins (in the lung): protect the airways from
infection
• belongs to the collectin family of proteins
• C-reactive protein (CRP): binds to phosphorylcholine on
microboes and coat and coats the microbes for phagocytosis by
macrophages, which express a receptor for CRP
Tuesday, July 3, 2012
33. PLASMA PROTEINS OF
THE INNATE IMMUNITY
• The circulating levels of many of these plasma protein
increase rapidly after infection
• protective response or acute phase response to
infection
• Extracellular bacteria and fungi are combated by
phagocytes and the complement system and by acute
phase proteins
• Defense against intracellular bacteria and viruses is
mediated by phagocytes and NK cells, with cytokines
providing the communications between the phagocytes
and NK cells
Tuesday, July 3, 2012
34. EVASION OF THE INNATE
IMMUNITY BY MICROBES
Tuesday, July 3, 2012
35. STIMULATING THE
ADAPTIVE IMMUNE
RESPONSE
• lnnate immune responses
generate molecules that
function as "second signals”
together with antigens, to
activate T and B lymphocytes
(co-stimulators)
• The requirement for these
second signals ensures that
adaptive immunity is elicited by
microbes (the natural inducers
of innate immune reactions)
and not by non-microbial
Tuesday, July 3, 2012
