INNATE IMMUNTY If any invader penetrate the bodys

INNATE IMMUNİTY

If any invader penetrate the body’s first line defense mechanisms: The second line or the first line immunologic defense Innate immunity l Always active or nearly active l Adaptive responses devolope usually later (after 96 hours) l

l - Innate immunity is prorammed to: To recognize broad range of molecules asscociated with pathogens To destroy the invaders rapidly: Activation of the phagocytic system and devoloping an inflmmatory response

Recognition of the microbes by innate immunity To recognize those structures, common to the various agent, but bor present in human l Phagocytes have LPS specific receptors l Phagocytes recognize mannose residues which are present only in glycoproteins of mammalian origine l

Phagocytes recognise and response also to: l Ds RNA, unmethylated Cp. G oligonucleotides l

The molecules of the microbes targeted by th immune system are - pathogen asscociated molecular patterns (PAMPs) l The receptors of the innate immunity for these molecules are “pattern recognition receptors” (PRRs) l The targets of the innate immunity are critical regarding the survival and infectivity of the microbes l

l Innate immunity can also recognise those molecules released from demaged or stressed cells of the body damage asscociated molecular patterns (DAMPs)

These receptors are encoded in the germline Receptors expressed on all cells of a certain type (not clonal) l Innate immunity does not reat against the host l İnnate immunity respond in the same way to repeated invasions l

l The main goals of the innate immunity - To induce inflammation To achieve antiviral defense -

Receptors expressed on Phagocytes, DC, lynphocytes, epithelial and endothelial cells l Receptors are expressed on different compartments of these cells l

Toll like receptors (TLR)

l TLR activates transcrition factors, which stimulate the expression of genes encoding cytokines, enzymes and other proteins Most important transcription factors are: Nuclear factor-kappa. B (NFkappa. B) and interferon response factor -3 (IRF-3) l

l NF-kappa. B promotes expression of cytokines and endothelialadhesion factor l IRF-3 stimulates type I interferons and cytokines with antiviral activity

Soluble defense mechanisms l l TYpe I interferons: DC (IFNalfa), fibroblasts (IFN-beta) Microbicidal molecules: Epithelial cells, PMN and macrophages secrete cystein rich peptides (defensines). Others are cathelicdine, lysozyme, DNAase, RNAase

Complement

Steps in Phagocytosis l Attachment l bacterial carbohydrates (lectins) l receptor for opsonins l fibronectin receptors l Fc receptors l Internalization l Digestion (phagocytic vacuole) (phagosome)

Antibacterial compounds of the phagolysosome I l Oxygen-dependent l Hydrogen compounds peroxide: NADPH oxidase and NADH l Superoxide l Hydroxil radicals (OH) _ _ _ l Activated halides (Cl , I , Br ): myeloperoxidase l Nitrous oxide

Antibacterial compounds of the phagolysosome II l Oxygen-independent compounds l Acids l Lysosome (degrades bacterial peptidoglycan) l Lactoferrin (chelates iron) l Defensin and other cationic proteins (damage membranes) l Proteases, elastase, cathepsin G

Phagocytosis & killing of bacteria

Macrophages in antibacterial response l Important antibacterial phagocytic cells l Killing by oxygen-dependent and oxygenindependent mechanisms l Production of IL-1, IL-6, and IL-12; TNF-a and TNF-b, and interferon-a l Activation of acute-phase and inflammatory responses l Presentation of antigen to CD 4 T cell

1. 2. 3. Expansion of capilaries to increase blood flow (seen as blushing or a rash) Increase in the permeability of the microvasculature structure to allow escape of fluid, plasma proteins, and leukocytes from the circulation edema Exit of leukocytes from the capillaries and their accumulation at the site of injury

Acute-Phase Reactants a 1 -antitrypsin l a 1 -glycoprotein l Amyloid A & P l Antithrombin III l C-reactive protein l C 1 esterase inhibitor l C 3 complement l Ceruloplasmin l Fibrinogen l Haptoglobulin l Orosomucoid l Plasminogen l Transferrin l Lypopolysaccharidebinding proteins l