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I mmunity

I mmunity. BY GHADA FAWZY. Innate immunity. Definition: Non specific early line of defense , it is the first line ofdefense against infection. This prevent entery of micro-organisms, or they eliminate them prior to occurance of the disease. Elements of innate immunity.

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I mmunity

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  1. Immunity BY GHADA FAWZY

  2. Innate immunity Definition: Non specific early line of defense , it is the first line ofdefense against infection. This prevent entery of micro-organisms, or they eliminate them prior to occurance of the disease

  3. Elements of innate immunity Anatomical Cellular Barriers components Secretory Molecules

  4. Anatomical barriers: • Skin: sweat, normal flora, intact skin. • Intestinal movements • Oscillation of bronco-pulmonary components

  5. Secretory molecules: • Organic acids&thiocyanate in saliva. • Low molecular weight fatty acids in GIT. • transferrin,lactoferrin,acute phase proteins,lysozymes,interferons,fibronectins, complements in serum • Interferons and tumor necrosis factor at site of inflammation.

  6. Transferrin&lactoferrin deprive organism from iron. • Interferon inhibits viral replication& activates other cells to kill pathogens • Lysozyme breaks down bacterial cell wall. • Fibronectin coat(opsonize) bacteria rapid phagocytosis. • TNF viral replication & phagocytosis. • Complements direct &indirect (via phagocytic cells destruction of organisms • Acute phase proteins(CRP)+complement compat infection.

  7. Antimicrobial peptides • Small molecular weight proteins with broad spectrum antimicrobial activity against viruses, bacteria&fungi • Types: *Definsins:( α&β). *cathelecidines. *saposines • Function: 1- preserving normal epithelium by promoting epithelial growth&angiogenesis. 2- secreted by moist airway epithelium as biofilm 3- act as chemokines attract neutrophils,dendreticcells&Tlymphocytes 4- antimicrobial activity: desrupting membrane integrity of their victims&interact with negatively charged targets within the microbes

  8. COMPLEMENTS • A system of 20 glycoproteins circulating in blood &bathing in tissue fluids that share in both innate &adaptive immunity through: • The classical complement pathway. Activated by Ag-Ab complexes. • The lectin pathway activated by plasma lectins (mannose binding proteins) that bind to microbial carbohydrates. • The alternative pathway activated by C3b binding to microbial surface and to Ab molecules. The end result is the production of a key enzyme (C3 convertase C3a&C3b , C4a, C5a.

  9. Function: • Binds to the suface of the microbes (the phagocytic cells express Rs for C3b- opsonization) to enhance phagocytosis. • Chemotactically attract the phagocytes (esp. C5a). • Triggers inflammation (release of inflammatory mediators from mast cells &increase vascular permeability(C3a, C4a&C5a). • Cause lysis of G-ve bacteria & human cells displaying foreign epitopes. • Play role in activation of naive B cells. • Remove harmfull immune complexes from the body

  10. Cytokines: • Interferon: antiviral activity&inhibit Th2 cytokines. • Interleukins: exert effect on leucocytes. Inflammatory mediators(IL-1,IL-6,IL-8&TNF-α). Anti-inflammatory mediators(IL-10) • Chemokines: with chemoattractantactivity • TNF: induce MHC-II expression on keratinocytes • CAM(cellular adhesion molecules): Surface glycoproteinswhich are important in the interaction of lymphocytes with APC, keratinocytes, endothelial cells and also in their trafficking in skin during inflammation Eg.: Cadherins, Ig, integrin, selectins

  11. Toll like recptors(TLs) • A family of receptors that play important role in recognition of micobial components • TLR2 (lipoproteins&peptidoglycan), TLR4(lipopolysaccharides),TLR5(flagellin) • Dederitic cells express many TLRs- on activation- presnt antigen to naive T cells

  12. Cellular components • Neutrophils (PMN): • Azurophilic granules : cationic proteins, definsins, proteases, lysozymes esp. Myeloperoxidase. • Secondary granules: lysozymes, NADPH oxidase cofactors, lacto-ferrin&B-12 binding protein . • Mononuclear phagocytes: monocytes&macrophages(have Rs for IgGFc, C, interferon, TNF and some bacterial componentsphagocytosis. • Eosinophils: Rs for IgEFccytotoxicity to parasites coated with IgE • Basophils: play role in immediate allergic reaction (anaphylaxis&angioedema) • Mast cells: type1 hypersensitivity reaction

  13. Natural killer cells(NK) • Resemble lymphocyte in morphology. • Participate in both innate &adaptive immunity • Concerned mainly in killing virus-infected cells&certain mutant cells Target cell Nk STRESS INDUCED GLYCOPROTEIN KILLER ACTIVATING RECEPTOR + + + + - - - - MHC1 KILLER INHIBITORY RECEPTOR

  14. Phagocyte response to infection • At site of infection phagocytes can attach bacteria via: • Rs for bacterial polysaccharides(scavenger rs) • Host proteins that act as opsonins (fibronectin,C,IgG) • After attachment , phagosomeformation,activation of respiratory burst(hexosemonophosphate shunt)&production of super oxide anion,H2O2,NO (MICOBICIDAL SUBSTANCES)

  15. Adaptive immunity • Antigen specific long term response mediated by lymphocytes&their products Antigen: a substance that react with antibody or antigen receptors on lymphocytes. Epitopes: the actual portion of antigen that react with antibodies or lymphocyte Rs. - the epitope Rs on B lymphocyte (BCR- sIg)& on T lymphocytes (TCR) Hapten: low molecular weight chemicals unable to provoke immune response unless they combine with protein Superantigen: unusual bacterial toxins bind directly to outside of MHC-ІІ & activate large number of T4 lymphocytes

  16. STEPS OF ADAPTIVE IMMUNITY • Step 1: antigen must encounter APC & naive lymphocytes • Step 2: clonal selection (recognition of Ag epitopes by naive lymphocytes) • Step 3:clonal expansion (proliferation, differentiation of B-T4-T8 to exert successful immune response • Step 4: • B cells Igs • T4 Th1&Th2 • T8 CytotoxicT lymphocytes(CTL) • Step 5:Formation of memory cells

  17. T4 IL12 IL4 Th1 Th2 IL2,IFNδ,TNF --- IL2,4.5.10,13 cell mediated humoral activate CTL,NK production of Igs &macrophages &activate eoinophils Th3: has suppressive effect on Th1&2 with production of IgE

  18. MHC molecules: Antigens located on HLA gene on chromosome 6 1- MHC-I: • expressed on all nucleated cells • Can bind endogenous antigens (viruses, intracellular bacteria,tumor antigens) • MHC-I+bound peptide stimulate TCR-CD8 (CELL MEDIATED IMMUNITY) 2- MHC-II: • expressed on macrophages,B&T cells • Can bind exogenous antigens • MHC-II+bound peptide recognized by TCR-CD4(humoral&cell mediated)

  19. Antigen presenting cells(APC): • They capture & process antigen for presentation toTcells • They produce signals required for proliferation &differentiation of lymphocytes

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