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Cytokines and Chemokines

Cytokines and Chemokines. Chapter 12 Karl A. Brokstad. Cytokines - Nomenclature. Monokines Lymphokines Cytokines (generic term) interleukins. Cytokine actions. Development of cellular and humoral immune responses Induction of inflammation Regulation of hematopoiesis

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Cytokines and Chemokines

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  1. Cytokines and Chemokines Chapter 12 Karl A. Brokstad

  2. Cytokines - Nomenclature • Monokines • Lymphokines • Cytokines (generic term) • interleukins

  3. Cytokine actions • Development of cellular and humoral immune responses • Induction of inflammation • Regulation of hematopoiesis • Control of cellular proliferation and differentiation • Induction of wound healing • Chemotaxis

  4. Main classes of cytokines • Interleukins (IL) • Interferons (IFN) • Chemokines (CXC, CC, C, CX3C) • Colony stimulating factors (CSF) • Tumor necrosis factors (TNF)

  5. properties • Antagonistic • Synergistic • Redundancy • Pleiotropism • Cascade action

  6. Figure 8-32

  7. Cytokine receptors • Type I cytokine receptors • Type II cytokine receptors • IL-1 family receptors • TNF receptor • Chemokine receptors

  8. Function Deliver effector cells Construct barrier Repair damage Stages Recognise pathogen/damage Express signalling molecules Increase vascular diameter, higher flow, lower velocity Vascular permeability Clothing microvessels Inflammation IL1, IL6, TNF-, INF-, IFN-, IFN-IL-8

  9. Figure 2-15

  10. Figure 2-39

  11. Figure 2-46

  12. Figure 2-48

  13. Inflammatory cytokines Pro-inflammatory: IL-1, IL-6, TNF-, IL-12, IL-18, (IFN-, chemokines) Anti-inflammatory: IL-4, IL-10, IL-13, TGF-

  14. Chemokines • Migration factors

  15. Figure 2-41 part 1 of 2

  16. Figure 2-41 part 2 of 2

  17. Th1-3 Cytokines Th1: IL-2, IFN- Th2: IL-4, IL-5, IL-13 Th3/Tr: IL-10, TGF- Th17: IL-17

  18. TH17 MAST NK NK TH0 M M TH1 TH3 TR1 TH2 TC B CD4+ T helper cells Cellular immunity IL-17 IL-23 Inflammation TGF-, IL-6, IL-1 Humoral immunity IL-12, IFN-, IL-18 IL-4 IFN- IL-4 IFN- IL-4, IL-10 IL-2, IFN-, TNF- IL-4, IL-5, IL-6, IL-10, IL-13 CD4+ CD25+ FOXP3+ CD4+ CD25+ Regulatory actions anti-inflammation TGF-, IL-10 40

  19. B B B Proliferation cytokines IL-2, IL-4, IL5 Diffentiating cytokines IL-2, IL-4, IL5 IL-4 TGF- IFN- IgM IgE / IgG1 IgA / IgG2b IgG2a / IgG3

  20. Functional categories • Mediate/regulate innate immunity • TNF, IL-1, IL-12, IFN type1, IL-10 • Mediate/regulate adaptive immunity • IL-2, IL-4/13, IFN-γ, TGF-β • Stimulates hematopoiesis • development / differetiation / maturation • IL-3, IL-7

  21. TNF • Innate immunity • Acute inflammation • Produced by monocytes/macrophages

  22. IL-1 • Innate immunity • Acute inflammation • fever IL-1α IL-1β IL-1RA sIL-1R IL-1R

  23. IL-12 Innate immunity Cell mediated immunity MØ, act.DC Th1  IFN-gamma

  24. IFN-α + IFN-β (type 1 IFN) Produced by virusinfected cells TLR-3, 7, 9

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