19- Cytokines

• Three Signals Needed for T cell activation

  • MHC to TCR
  • Second signal: CD80 (APC) to CD28 (TH)
  • Cytokines
• Cytokines

  Depends on stimulation of APC, results in different Th types
• What do activated T cells Do?

  1. Make lots of Self

  2. Autocrine cytokine induction stimulates self growth

  3. Increase IL-2: causes proliferation

  4. Decide the Best TH Cell to Become
• Decide the Best TH Cell to Become

  Depends on what cytokines are released by the APC that activates the T cell: direct T cell polarization
• Virus/Bacteria

  • APC produce IL-12: TH1
• Worms

  • APC or eosinophil produce IL-4: TH2
• Parasites and allergy aren't as big of an issue and body will be hesitant to respond
• TH1 Subset: Intracellular pathogens


  • Cell mediated response
  • Induced by IL-12 and IFNy
  • Strong production of more IFNy
  • Enhances phagocytosis and complement (isotype switching to IgG)
  • Helps activate CD8 T cells (antiviral cytotoxic Tc)
• IFNY:

  1. Activates macrophages which then produce IL-12

  2. IL-12 activates NK cells and T cells which then produce IFNy and creates positive feed back loop back up to macrophages

  3. Supresses Th2 response: don't need it, why waste the energy
• Other involved cytokines produced by TH1 cell:

  • IL-2: T cell proliferation
  • IL-3 induce macrophage differentiation
  • TNFa+TNF B: activate endothelium to induce macrophage binding
• TH2 Subset

  • Humoral response: Activates mast cells and eosinophils which degranulate
  • Signature cytokine produced: IL-4
  • Stimulates IgE in B cells
  • Also produced by mast cells, CD4 Th2 cells, Basophils and eosinophils
  • Supresses TH1 proliferation
• IL-5:

  • Stimulates growth and differentiation of eosinophils
  • Activates eosinophils
  • Stimulates IgE production in B cells
  • Supresses Th1 proliferation
• TH17 Subtype

  • Early Response
  • Produce IL-17
  • Activates and recruits neutrophils (phagocytic)
  • Targets extracellular bacteria and fungi
  • Induced by IL-1B, IL-6, TGFB ( early inflammatory cytokines)
• Treg Subtypes

  • Produces TGFB and IL-10
  • Supresses APC, T and B cell responses
  • Limits immune response and prevent autoimmunity
  • Inhibits immature dendritic cells which then cannot activate T cells
  • Induced by TGFB from APC
• TH17 vs Treg

  • Both need TGFB for differentiation, but the addition of IL-6 is the switch that induces TH17
  • Oppose each other:
  • Healthy: maintain Treg to keep inflammation down
  • Infected: 11-6 will stimulate more TH17
• T reg

  TGF-B

  IL-10, TGF-B

  Regulates and Supresses immune response
• Th 17

  Il-1B, IL-6, TGF-B

  IL-17

  Inflammation, for extracellular bacteria, fungi
• Th2

  IL-4

  IL-4, IL-5

  Allergic and anti-parasitic respone
• Th1

  IFN-y, IL-12

  IFN-y, TNF-a

  Cell-mediated immunity, macrophage activates, inflammation