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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 3- Haqqi), coagulation system, cytokines (lectures 14 & 15- Nyland) • Cellular components • Neutrophils, monocytes & macrophages, NK cells, eosinophils

  5. Anatomical barriers- mechanical

  6. Anatomical barriers- chemical

  7. Anatomical barriers- biological

  8. Humoral components

  9. Cells of the immune system

  10. Cellular components

  11. Phagocytosis and Intracellular killing Neutrophils and Macrophages

  12. Phagocyte response to infection • The SOS signals • N-formylmethionine-containing peptides • Clotting system peptides • Complement products • Cytokines released by tissue macrophages • Phagocyte response • Vascular adherence • Diapedesis • Chemotaxis • Activation • Phagocytosis and killing Source: SOM PathMicro online textbook

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

  14. 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*

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

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

  17. O2-independent killing

  18. Summary of intracellular killing pathways

  19. Nitric oxide-dependent killing • Bacteria binds to macrophage • Production of TNF-alpha • UpregulatesiNOS • Release of NO • NO is toxic to infected cells in vicinity of macrophage NO synthetase O2 + L-arginineNO + citrulline Macrophage TNF IFN-gamma

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

  21. Innate response to virus infection and altered self • Infected or altered self (transformed) cell downregulated MHC • NK does not receive inhibitory signal • Signals kill infected cell NK R Inhibitory R NK cell No MHC Infected/transformed cell

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

  23. Determinants recognized by theinnate immune response • PAMPs- pathogen associated molecular patterns • PRRs- pattern recognition receptors

  24. Pathogen-associated molecular patterns (PAMPs) • Non-specific (not antigen specific) receptor recognition • Part of innate antimicrobial defense • Toll-like receptors on macrophages bind pathogen and cause activation

  25. Determinants recognized by theinnate immune system

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

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