Cytokines

• Mediators and regulators of innate immunity

  • TNF
  • Type 1 IFN
  • chemokines
  • IL-1
  • IL-6
  • IL-12
  • IL-15
  • IL-18
• mediators and regulators of adaptive immunity

  • IL-2
  • IL-4
  • IL-5
  • IFN-g
  • TGF-B
  • LT(TNF-B)
  • IL-13
• Stimulators of hematopoiesis

  • granulocyte-CSF (G-CSF)
  • macrophage-CSF (M-CSF)
  • granulocyte-macrophage-CSF (GM-CSF)
  • erythropoietin (EPO)
  • TPO
  • stem cell factor (SCF)
• Both TH1 and TH2 subsets secrete IL-3 and GM-CSF
• TH1 subset is responsible for:

  • many cell-mediated functions
  • production of opsonization-promoting IgG antibodies
  • promotion of excessive inflammation and tissue injury
• Secretions of TH1 subset

  • IFN-y
  • activates macrophages, to increase microbicidal activity
  • up-regulate the level of class II MHC
  • induce antibody-class switching to IgG classes enhancing phagocytosis and fixation of complement
  • exhibits expansion of the TH2 population
  • IL-12
  • induces TH cells to differentiate into the TH1 subset
  • TNF-B and IFN-y
  • mediating inflammation
  • IL-2 and IFN-y
  • promote differentiation of fully cytotoxic TC cells from CD8+ precursors
• TH2 subset is responsible for:

  • eosinophil activation and differentiation
  • providing help to B cells
  • supports allergic reactions
• Secretions of TH2 subset

  • IL-4 and IL-5
  • induces production of IgE and supports eosinophil-mediated attack on helminth
  • increases Fc receptors on eosinophils
  • IL-4
  • promotes class switch from IgM to IgG and IgE
  • IL-4 and IL-10
  • suppress expansion of TH1 cell
• TH cell that does not show either a TH1 or TH2 profile

  TH0
• Comparing functions of TH1 and TH2 subsets

  • Help for total antibody production - both but TH2 better
  • help for IgE production - TH2
  • help for IgG2a production - both but TH1 better
  • eosinophil and mast-cell production - TH2
  • macrophage activation - TH1
  • delayed-type hypersensitivity - TH1
  • TC-cell activation - TH1
• Cytokines secreted by TH1

  • IL-2
  • IFN
  • TNF
  • GM-CSF
  • IL-3
• Cytokines secreted by TH2

  • GM-CSF
  • IL-3
  • IL-4
  • IL-5
  • IL-10
  • IL-13
• What chain is shared by the IL-2 receptor family


  y (gamma)
• Proinflammatory cytokines

  • TNF
  • IL-1
  • IL-6
• TYPE I IFNs

  Major cellular sources of Type I IFNs

  • IFN-a: mononuclear phagocytes
  • IFN-B: fibroblasts

  Potent stimulus

  • viral infection

  Function

  • mediate the early innate immune response to viral infections
  • increase expression of class I MHC molecules
  • stimulates the development of TH1 cells in human
• IL-2

  • growth factor for antigen-stimulated T lymphocytes
  • responsible for T cell clonal expansion after antigen recognition
• IFN-y is a principal macrophage-activating cytokine
• IFN-y inhibits the propagation of Leishmania
• Cytokine associated diseases

  • IFN-B: multiple sclerosis
  • IFN-y: chromic granulomatous disease
  • IL-2: kidney cancer, melanoma
  • IL-11: thrombocytopenia
  • TNFa mAb: infliximab for rheumatoid arthritis and Crohn's disease
• Bacterial Septic Shock

  • develops because bacterial cell-wall endotoxins stimulate macrophages to overproduce IL-1 and TNF-
• cytokine associated with myeloid cancer: IL-6