Lecture 3

Define innate immunity and describe differences between innate and adaptive immunities.

Describe the role of the epithelial layer as a barrier to infection.

Epithelium is a general name for the layers of cells that lines the outer surfaces and the inner
cavities of the body. Skin is composed of impenetrable barrier of epithelium protected by layer
of keratinized cells. Epithelial also contain tissues such as mucosal surface which continuous bath
in mucous which contains glycoproteins, proteoglycans and enzymes that protect the epithelial
cells from damaged and limit infection.

All epithelial surfaces secrete antimicrobial substances. The sebum secreted by sebaceous glands
associated with hair follicle contains fatty acids and lactic acids both of which inhibit bacterial
growth on the surface of the skin.

All epithelia surfaces secrete antimicrobial peptide that kill bacteria, fungi, and enveloped
viruses by perturbing their membranes. Tears and saliva contain lysozyme, an enzyme that kill
bacteria by degrading their cell walls. Microorganisms are also deterred by the acidic
environments within the stomach, the vagina and the skin.

Understand the biology and action of defensins.

Large family, small peptides. Gene copy numbers vary among individual. Two subclasses: alpha
and beta

Alpha-defensins: neutrophils, and Paneth cells (small intestine).

Beta-defensin: various epithelial cells

Mechanism of action: proform cleaved to active-form

 Activation: act both intracellular and extracellular by penetration into microbial membrane and
disrupt the membrane integrity.

Know the major functions of macrophages, neutrophils, and NK cells.

Neutrophil: recognizing and phagocytosis: phagocytosis relies on signaling through cell surface
receptors that recognize the Fc region of bound antibody, or the C3b o iC3b fragment on
opsonized pathogens.

1. Recognition of bacterial by using cell surface receptor

2. Phagocytosis of invading pathogen and dead cells
3. Production of cytokines to initiates tissue inflammation
Macrophage:
1. Recognition of pathogens by Pathogen Recognition Receptor (PRR).
2. Release of soluble mediators
3. Phagocytosis

NK Cells:

1. Cell cytotoxicity against virally infected cells.

2. Cytokine production
3. Producing important cytokine IFN-gamma (activating Macrophages)
4. Activates by INF alpha, IL-12, TNF-alpha
5. Antibody-dependent cell mediated cytotoxicity, ADCC.
6. Fxn is inhibited by IL-10

Describe how macrophages or neutrophils kill the engulfed bacteria (respiratory burst).

Neutrophils: phagocytosis cause intracellular oxidative burst which generates highly reactive
oxygen intermediates that contribute to the microbial killing and to tissue injury during
inflammation.

Activates NADPH oxidase convert O2 to superoxide and hydrogen peroxide which responsible
for destroy pathogens.

Describe how NK cells distinguish healthy and

unhealthy cells

Interaction of NK cell with uninfected cell that expressed no MIC ligand for NKG2D

Interaction of NK cell with infected cell that express MIC ligands for NKG2D. Activated NKG2D
cause release of lytic granule to kill virus infected cell.
Innate Immunity

Defensins

Macrophage

Neutrophils

Natural Killer (NK) Cells

Phagocytosis

Interferons

Epithelial layer

Respiratory burst