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Innate immunity

Innate immunity. Properties of innate immunity Components of innate immunity Epithelial barriers Cellular mechanisms Humoral mechanisms Role of innate immunity in stimulating adaptive immune response. Principle mechanisms of innate and adaptive immunity. Mechanisms of innate immunity.

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Innate immunity

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  1. Innate immunity • Properties of innate immunity • Components of innate immunity • Epithelial barriers • Cellular mechanisms • Humoral mechanisms • Role of innate immunity in stimulating adaptive immune response

  2. Principle mechanisms of innate and adaptive immunity

  3. Mechanisms of innate immunity - phylogenetically older - exist before or react immediately after contact with pathogen - are not enhanced upon repetead contact with pathogen (no memory) - react predominantly to infectious agents - first line of defense - stimulate and shape adaptive imunity

  4. Components of innate immunity - epithelial barriers (skin and mucosal membranes) - cells (phagocytes,NK cells...) - humoral components (complement, cytokines etc.)

  5. Functions of epithelia in innate immunty • physical barrier

  6. Functions of epithelia in innate immunty • physical barrier • chemical barrier • (production of antimicrobial peptides)

  7. Functions of epithelia in innate immunty • physical barrier • chemical barrier • (production of antimicrobial peptides) • intraepithelial lymphocytes - normal bacterial flora

  8. Cells of innate immunity Pricipal function(s) Cell type Phagocytosis, inflammation, T-cell activation, tissue repair Monocytes/Macrophages Neutrophils Phagocytosis, inflammation NK cells Killing of infected or tumor cells Dendritic cells Phagocytosis, activation of naive T-cells Mast cells Inflammation Eosinophils Defense against parasites

  9. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen

  10. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen (macrophages and dendritic cells) - molecular patterns and receptors

  11. Molecular patterns Structures common for certain groups/classes of pathogens • essential for their life, replication and/or infectivity • not present on human cells Examples: Lipoproteins structures of bacterial cell wall (LPS, peptidoglycan, flagellin...) Flagellin nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)

  12. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen 3. Phagocytosisand killing of a pathogen(macrophages) • reactive oxygen species (ROS), nitric oxide (NO) • and lysosomal enzymes

  13. Phagocytosis and killing of microbes Pathogen recognition

  14. Phagocytosis and killing of microbes Zipping of membrane around microbe

  15. Phagocytosis and killing of microbes Ingestion of microbe

  16. Phagocytosis and killing of microbes Fusion of phagosome with lysosome

  17. Phagocytosis and killing of microbes Phagocyte activation

  18. Phagocytosis and killing of microbes Killing of microbe http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_3.html

  19. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen 3. Phagocytosisand killing of a pathogen 4. Induction of inflammation(macrophages) - production of pro-inflammatory cytokines (TNF, IL-1, chemokines...)

  20. Inflammation induction Proinflammatory cytokines TNF ― Tumor Necrosis Factor IL-1 ― Interleukin-1 Chemokines ― Chemotactic cytokines

  21. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen 3. Phagocytosisand killing of a pathogen 4. Inflammation induction 5. Attraction of cells to infection site - adhesive molecules (selectinsand integrins) andchemokines

  22. Leukocytes arrive at the site of infection (extravasation) http://www.youtube.com/watch?v=WEGGMaRX8f0 http://www.youtube.com/watch?NR=1&v=DMvixApKzKs Various adhesive molecules Integrins Selectins In some inflammatory diseases therapy is directed against proinflammatory cytokines or adhesive molecules (eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis) Weak binding and rolling Activation and firm binding Transmigration Endothelium TNF & IL-1 Arrival to the site of infection Macrophages Chemokines

  23. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen 3. Phagocytosisand killing of a pathogen 4. Inflammation induction 5. Attraction of cells to infection site 6. Pathogen elimination and/oradaptive immunity activation(dendritic cells) - cytokines, costimulatory molecules...

  24. Role of phagocytes in innate immunity Order of events in infection 1. Entry of pathogen 2. Recognition of pathogen 3. Phagocytosisand killing of a pathogen 4. Inflammation induction 5. Attraction of cells to infection site 6. Pathogen elimination and/oradaptive immunity activation 7. Tissue repair and remodeling(macrophages) - enzymesand cytokines (growth factors, metaloproteinases...)

  25. Role of NK cells in innate immunity NK – Natural killer Killing of cellsinfected by intracellular pathogens (eg. viruses) and tumor cells

  26. Role of NK cells in innate immunity NK – Natural killer Killing of cellsinfected by intracellular pathogens (eg. viruses) and tumor cells Activation of macrophages (by IFN-γ)

  27. NK cell killer function Depends on balanse of signals by activating and inhibitory receptors Inhibitory Activating

  28. NK cell killer function Depends on balanse of signals by activating and inhibitory receptors Activating Inhibitory NK cell is inhibited NO KILLING

  29. NK cell killer function Depends on balanse of signals by activating and inhibitory receptors Inhibitory Activating NK cell is activated KILLING

  30. NK cell killer function Depends on balanse of signals by activating and inhibitory receptors Inhibitory Activating • activating receptors recognize stress-derrived structures on cells (including infected and malignant cells) - inhibitory receptors recognize MHC class one molecule

  31. Mechanism of NK cell recognition

  32. Mechanism of NK cell recognition

  33. NK cell killer function Apoptosis induction in infected and tumor cells Killing mechanisms same as in cytotoxic T-cells - Perforin and granzymes - FasL and Fas perforin NK cell granzymes Infected or tumor cell apoptosis FasL Fas

  34. Humoral mechanism ofinnate immunity • complement proteins (8th week seminar) - cytokines - other plasma proteins (CRP, MBL etc.)

  35. Cytokines in innate immunity Inflammation induction (TNF, IL-1, chemokines...)

  36. Cytokines in innate immunity Macrophage and NK cell Activation (IL-12 and IFN-γ) Inflammation induction (TNF, IL-1, chemokines...) Antiviral effects (IFN type I, IFN-α and IFN-β) (eg. INF-αin HCV therapy) Differentiationof T-cell subpopulation (eg. IL-12)

  37. Role of innate immunity in stimulation of adaptive immune response T or B-cells need two signals for activation First signal antigen recognition Second signal derrived by innate immunity

  38. Thanks for your attention! Questions?

  39. 1. Receptors on innate immunity cells recognize a. Production of enzymes, ROS and NO 2. Epithelial cells provide chemical barrier for pathogens by b. Kill our own virus-infected cells 3. Macrophages stimmulate inflammation by production of c. Polysaccharide capsule production 4. Macrophages kill phagocytosed microbes by d. TNF, IL-1 and other mediators 5. NK cells e. molecules that provide “second signal” 6. NK cells are activated f. NK and T- cells 7. Chemokynes are important for g. Structures that a group of pathogens has in common 8. IL-12 produced by macrophages stimulates h. When a target cell does not express MHC class I 9. Bacteria can avoid phagocytosis by i. Leukocyte migration 10. Innate immunity cells stimulate adaptive immunity by j. Peptide antibiotics production 1.____ 2.____ 3.____ 4.____ 5.____ 6.____ 7.____ 8.____ 9.____ 10.____ b h i f c e g j d a

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