2.

INNATE IMMUNITY
2.1 – INNATE IMMUNITY
 No need for prolonged induction of pathogen
 No antigen specificity
 Acts quickly, in 0-4 hours
 Failure to eliminate a foreign antigen results in adaptive response kicking in
 Dependence on germ line encoded receptors
 Able to discriminate between host and pathogen and commensals and pathogens

ANATOMICAL BARRIERS AGAINST INFECTION

System/Organ Cell Mechanism Type of
Type/Component Defense
Squamous Physical Barriers Mechanical
Skin Epithelium Desquamation
Sweat Antimicrobial fatty acids Chemical
Skin and Normal Flora Antimicrobial substances Biological
Mucous Competition for nutrients
Membranes and colonization
Non-ciliated Peristalsis Mechanical
Epithelium (ex. GI
Tract)
Ciliated Epithelium Mucocilliary elevator Mechanical
(ex. respiratory tract)
Epitheliums (ex Flushing actions of tears, Mechanical
nasopharynx) saliva, mucous, urine
Mucous
HCl (parietal cells), Low pH Chemical
Membranes
tears, and saliva Lysozyme and phospholipase
Defensins (in Antimicrobial Chemical
respiratory and GI
tract)
Surfactants; Opsonin (a substance that Chemical
phospholipoproteins promotes the phagocytosis of
(lungs) antigens by binding to them)
Cell Inductive: Toll-Like Receptors that recognize Biological
membranes Receptors pathogens

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HUMORAL IMMUNITY: host defenses mediated by antibodies and other factors in the
plasma, lymph, and tissue fluids. Composed of soluble innate elements (collectins,
complement) and adaptive antibodies.

HUMORAL COMPONENTS
Component Mechanism
 Lysis of bacteria and some viruses
Complement  Opsonin
 Increase in vascular permeability
 Recruitment and activation of phagocytic cells
 Increase vascular permeability
Coagulation system  Recruitment of phagocytic
 B-lysin from platelits – a cationic detergent
Lactoferrin and transferrin  Compete with bacteria for iron
Lysozyme  Breaks down bacterial cell wall
Cytokines  Various effects

CELLULAR IMMUNITY: host defenses mediated by adaptive antigen-specific T cells

and innate non-specific cells which involves the activation of immune cells that can
release various cytokines in response to an antigen. Also includes the sentinel innate
immune cells of tissues, which act like guards.

CELLULAR COMPONENTS
Cell Mechanism
Neutrophils  Phagocytosis and intracellular killing
 Inflammation and tissue damage
Macrophages and  Phagocytosis and intracellular killing
Dendritic Cells  Extracellular killing of infected or altered-self
targets
 Tissue repair
 Antigen presentation for specific immune responses
Natural Killer (NK) Cells  Killing of virus-infected altered-self targets
Eosinophils, Basophils,  Killing of certain parasites
and Mast Cells

COMPONENTS RECOGNIZED BY THE INNATE IMMUNE RESPONSE

PAMPs: Pathogen Associated Molecular Patterns are used in innate immune
recognition of bacterial cell wall components

PRRs: Pattern Recognition Receptors which have non-specific recognition

 NODs: nucleotide-binding oligomerization domain
 TLRs: toll-like receptors; activated by specific microbial ligands
o TLRs that recognize nucleic acids are localized inside cells

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2.2 - IMMUNE RESPONSE TO DAMAGE
ACUTE INFLAMMATION: rich in neutrophils (dedicated to killing host bacteria and
are short-lived; often damage host tissue as a by-product); later it is more monocytes
and macrophages. This type of inflammation is controlled by chemokines expressed by
endothelial and epithelial cells.

B cells

Cytotoxic T
cells

Helper T cells

Mononuclear phagocytes

Neutrophils
Days 0 47 Weeks: 246
:

Monocytes are multi-potential, depending on cytokine signals

 +IFN-γ: Vigorous killing phenotype similar to neutrophils
 +IL-10: Wound-healing type phenotype to clean up after infection is cleared
 +GM-CSF + IL-4: Dendritic Cell phenotype; propagates adaptive priming
 +CSF: Macrophage phenotype

How do cells get to the site of infection?

 Leukocytes circulate through the blood and secondary lymphoid organs
 Usually an injury or infection does not occur first in the blood stream but
rather in various organs and tissues of the body
 Problem: leukocytes are contained within the blood vessels and restrained from
attacking the infection at its source, but if the blood vessels become freely
permeable to cells and fluid, it would be fatal (anaphylactic shock: system
vasodilation which results in low blood pressure)
 Cells have to get out of the blood stream at the right place and time without
letting everything else escape: extravasation

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2.3 - SEPSIS SYNDROME
 Systemic or blood infection
 Bacterial septicaemia leads to activation of TLRs on monocytes in the blood
 Systemic release of TNF and IL-1 leads to ‘inflammation’ all over the body
 Shock from loss of blood pressure (vasodilation and leakage of fluid into tissues)
 Leads to multi-organ failure and death

PHAGOCYTOSIS: process by which leukocytes contact, surround, consume, and

destroy microorganisms and other foreign particles

2.4 - SIX STEPS OF PHAGOCYTOSIS:

1. Activation
 By inflammatory mediators
(cytokines); stimulates production of
glycoprotein receptors on leukocyte
cell membrane -- increased
adherence to surfaces and foreign
objects (such as bacteria) and
triggering of respiratory burst.
2. Chemotaxis
 Rapid migration along chemical
gradient towards tissues with a high
concentration of inflammatory
mediators: chemokines
3. Recognition and adherence
 Mediated by glycoprotein receptors
on phagocyte membrane, which displays several TLRs
4. Ingestion
 Pseudopodia engulf attached bacterium and tips meet and fuse  phagosome,
which separates from cell membrane and becomes an internal structure
5. Killing and digestion
 Phagosomes fuses with lysosome (containing microbiocidal chemicals) 
phagolysosome, which usually causes bacterial death and digestions
6. Expulsion of debris
 Phagolysosome fuses with cell membrane and expels indigestible debris
(exocytosis)

Inside the phagosomes, enzymes transfer oxygen into reactive oxygen or nitrogen
species, which can kill microbes.

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2. 5 - PHAGOCYTOSIS NO-DEPENDENT KILLING AND KILLING
1. Bacteria binds to macrophage
2. Production of TNF-α
3. Upregulates iNOS
4. Release of NO (Nitric Oxide)
o NO is toxic to infected cells in vicinity of macrophage

2.6 - INNATE RESPONSE TO VIRUS INFECTION

1. Infected or altered self (cancerous) cell downregulates MHC
2. NK does not receive inhibitory signal
3. Signals kill infected cell