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Innate Immune Response

Innate Immune Response. Jennifer Nyland, PhD Office: Bldg #1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu. Teaching objectives. Understand the mechanisms of combating infection/disease How does the body kill pathogens?

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Innate Immune Response

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  1. Innate Immune Response Jennifer Nyland, PhD Office: Bldg #1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu

  2. Teaching objectives • Understand the mechanisms of combating infection/disease • How does the body kill pathogens? • To know the humoral and cellular components of the innate immune response • What are the key features and timing? • What is the mechanism of action of the components of the innate immune response?

  3. Overview of the immune system

  4. Innate host defenses against infection • Anatomical barriers • Mechanical, chemical, biological • Humoral components • Complement (lecture 9- Robinson), coagulation system, cytokines (lectures 7 & 8- Nyland) • Cellular components • Neutrophils, monocytes & macrophages, NK cells, eosinophils

  5. Anatomical barriers- mechanical

  6. Anatomical barriers- chemical

  7. Anatomical barriers- biological

  8. Innate host defenses against infection • Anatomical barriers • Mechanical, chemical, biological • Humoral components • Complement (lecture 9- Robinson), coagulation system, cytokines (lectures 7 & 8- Nyland) • Cellular components • Neutrophils, monocytes & macrophages, NK cells, eosinophils

  9. Humoral components

  10. Innate host defenses against infection • Anatomical barriers • Mechanical, chemical, biological • Humoral components • Complement (lecture 9- Robinson), coagulation system, cytokines (lectures 7 & 8- Nyland) • Cellular components • Neutrophils, monocytes & macrophages, NK cells, eosinophils

  11. Cells of the immune system

  12. Innate cellular components

  13. Phagocytosis and Intracellular killing Neutrophils and Macrophages

  14. Phagocyte response to infection • Vascular adherence • The SOS signals • N-formylmethionine-containing peptides • Clotting system peptides • Complement products • Cytokines 2. diapedesis 3. chemotaxis 4. activation, phagocytosis & killing Source: SOM PathMicro online textbook

  15. Phagocytosis A. • Attachment via receptors • FcR, complement R, scavenger R, Toll-like R • Pseudopod extension • Phagosome formation • Granule fusion and Phagolysosome formation B. Cytoplasm C. D.

  16. G-6-P-dehydrogenase NADPH oxidase Cytochrome B Superoxide dismutase Glucose + NADP+ NADPH +O2 2O2- + 2H+ 2O2- + H2O2 OH* + OH-+1O2 Pentose-P + NADPH NADP+ + O2- H2O2+1O2 Respiratory burst O2-dependent MPO-independent reactions Toxic compounds: superoxide anion O2-, hydrogen peroxide H2O2, singlet oxygen1O2 , hydroxyl radical OH*

  17. myeloperoxidase H2O2+ Cl- 2OCl- + H2O 1O2 + Cl-+H2O OCl-+H2O Respiratory burst O2-dependent MPO-dependent reactions Toxic compounds: hypochlorous acid OCl-, singlet oxygen1O2

  18. Superoxide dismutase Catalase O2- + 2H+ 2H2O2 H2O2+O2 H2O+O2 Respiratory burst Detoxification reactions

  19. O2-independent killing

  20. Summary of intracellular killing pathways

  21. Nitric oxide-dependent killing • NO is toxic to infected cells in vicinity of macrophage TNFα NO Synthase Arginine NO (rapid diffusion)

  22. Non-specific killer cells NK cells Eosinophils Mast cells

  23. Innate response to virus infection and altered self MICA MICB KAR KIR perforin Killing of Infected cell X

  24. Innate response to intracellular pathogens • Activated NK cells (LAKs) • Release Lytic granule components • perforin • granzymes

  25. Innate response to extracellular microorganisms (parasites) • Activated eosinophils release granule components • Major basic protein • Major component of granules • Eosinophil peroxidase • Cationic hemoprotein • Eosinophil cationic protein • ribonuclease

  26. Pathogen recognition by innate immune system PAMPs PRRs

  27. PAMPs- pathogen associated molecular patterns • LPS: • Gram-pos: • Gram-neg: (gly)5 CO-NH

  28. PRRs – pathogen recognition receptors • Soluble receptors: • complement, mannose binding protein • Host cell receptors: • TLRs, scavenger O-antigen Core oligosaccharide Lipid A

  29. Determinants recognized by the innate immune system • Non-specific (not antigen specific) receptor recognition • Part of innate antimicrobial defense • Toll-like receptors on macrophages bind pathogen and cause activation

  30. Determinants recognized by theinnate immune system

  31. Immune response to damage • Dependent on what, where and how bad • Phased response with critical timing • Requires chemokine signaling, receptor binding, etc Days: 0 4 7 Weeks: 2 4 6

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