2. Immunity to bacteria

4. Barrier defenses of human body

5. Antibacterial Responses “ Protection is initiated on activation of innate responses on a local basis and progress to acute-phase and antigen specific responses on a systemic scale ”

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

7. Bacterial components that activate Protective Responses I Direct activation –LPS –Lipoteichoic acid –Lipoarabinomannan –Glycolipids and glycopeptides –Polyanions –N-Formyl peptides

8. Bacterial components that activate Protective Responses II Chemotactic –Peptidoglycan fragments –Cell surface activation of alternative pathways of complement (C3a, C5a)

9. Complement in antibacterial response Alternative and Lectin pathways activated by bacterial surfaces Classic pathway activated later by antibody-antigen complexes Production of chemotactic and anaphylotoxic proteins (C3a, C5a) Opsonization of bacteria (C3b) Promotion of killing of gram-negative bacteria Activation of B cells (C3d)

10. Complement cascade

11. Neutrophil diapedesis in response to inflamatory signals

12. Phagocytes & Phagocytosis PMNs, monocytes, and eosinophils are the first cells to appear in response to acute inflammation; they are followed later by macrophages

13. Neutrophils major antibacterial response an increased number of neutrophils in the blood, body fluids or tissue indicates: “bacterial infection” “left shift”

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

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

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

17. Phagocytosis & killing of bacteria

18. Macrophages in antibacterial response Important antibacterial phagocytic cells –Killing by oxygen-dependent and oxygen- independent mechanisms –Production of IL-1, IL-6, and IL-12; TNF-  and TNF- , and interferon-  –Activation of acute-phase and inflammatory responses –Presentation of antigen to CD4 T cell

19. Antibacterial responses

20. Acute-Phase Reactants  1 -antitrypsin  1 -glycoprotein Amyloid A & P Antithrombin  C-reactive protein C1 esterase inhibitor C3 complement Ceruloplasmin Fibrinogen Haptoglobulin Orosomucoid Plasminogen Transferrin Lypopolysaccharide- binding proteins

21. Specific Immune Responses to Bacteria I Macrophages move to lymph nodes and interact with CD4 T cells after ingestion of bacteria initially:Macroph(APC).CD4 TH0 cells antigenic peptides + class  MHC TCR + CD4, on TH0

22. Specific Immune Responses to Bacteria II costimulatory signals from the interaction of CD28 (T cells) B7 molecule (macrophage) + IL -1, IL -12 TH0 produce IL-2, IFN-  and IL-4 B cells produce IgM LPS and cell wall polysaccharides activate B cells

23. Specific Immune Responses to Bacteria III TH0TH1( IL-12 & IFN-  ) –activation of Macrophages, T cells, B cells –important for intracellular infections CD4 TH2 T-cell response –occur later –initiated by the B cell presentation of antigen –presentation to TH2 cell (Ag + class II MHC) –TH2 IL-4, IL-5, IL-6, IL-10IgG, Plasma-cells, memory cells

24. T cells in antibacterial response TH1 CD4 responses important for intracellular bacterial infections TH2 CD4 response important for all bacterial infections CD8 cytolytic T cells not very important

25. Antibody in antibacterial response primary protection against extracellular bacteria and reinfection Binding to surface structures of bacteria (fimbriae,lipoteichoic acid, capsule) –Blocking attachment –Opsonization of bacteria for phagocytosis –Promotion of complement action –Promotion of clearence of bacteria –Neutralization of toxins and toxic enzymes

26. Bacterial Immunopathogenesis “tissue and systemic damage” IL-1, IL-6 and TNF-  life-threatening in systemic infection endotoxinmacrph.TNF-  in the blood symptomes of sepsis antibodies which share determinants with human proteinspost-streptococcal glomerulonephritis and rheumatic fever superantigensSTSS

27. Bacterial Evasion of Protective Responses 1.the inhibition of phagocytosis and intracellular killing in the phagocyte 2.inactivation of complement function 3.cleavage of IgA 4.intracellular growth (avoidance of antibody) 5.change in bacterial antigenic appearence