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Principles of Immunology Cytokines 2/2/06

Principles of Immunology Cytokines 2/2/06. “Live simply so others can simply live.” Anonymous. Word List. Autocrine Endocrine Immunoglobulin superfamily Interleukin Paracrine Pleiotropy Stem cell factor. Chemical Structure. Low molecular weight proteins, <30kD

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Principles of Immunology Cytokines 2/2/06

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  1. Principles of ImmunologyCytokines2/2/06 “Live simply so others can simply live.” Anonymous

  2. Word List • Autocrine • Endocrine • Immunoglobulin superfamily • Interleukin • Paracrine • Pleiotropy • Stem cell factor

  3. Chemical Structure • Low molecular weight proteins, <30kD • High affinity for receptors • Active in picomole amounts

  4. Chain of Cytokine Action Stimulus>Cytokine-producing cell> Cytokine>Target cell>Receptor> Biological effect(s)

  5. Names of Cytokines • Source • e.g.,Lymphokines • Function • e.g.,Chemokines • Intercellular action • e.g., Interleukins

  6. Action of Cytokines • Autocrine • Affects the generating cell (self) • Paracrine • Affects cells in the immediate vicinity • Endocrine • Affects cells remote from the secreting cell

  7. Action of Cytokines • Pleiotropy • Affects multiple cell types • Redundancy • Multiple cytokines affects cells of the same type • Synergy • Cytokines acting in concert on the same cell • Antagonism • Competing actions • Cascading • Cytokines acting sequentially

  8. Cytokine-generating Cells • Innate immunity • Macrophages • Endothelial cells • Fibroblasts • Adaptive immunity • T lymphocytes • Macrophages • NK cells

  9. Cytokine Receptors • Ig super family • Class I- hematopoietin • Class II-interferon • TNF • Chemokine

  10. Cytokine Receptors • Multimeric receptors • Common signal-transducing subunits • Unique high affinity subunits • High affinity subunits associated with activation of target cell

  11. Signal Transduction • Initiated by cytokine binding • Activates JAK (Janus kinase) • Phosphorylation of tyrosine • Binding of STAT(Signal transducers and activators of transcription) • Translocation of STAT to cell’s DNA • Transcription of specific target genes

  12. Role of Cytokines in Hematopoiesis • SCF (Stem cell factor) • GM-CSF (Granulocyte-macrophage colony-stimulating factor) • IL-3 (Interleukin 3) • IL-5 (Interleukin 5) • IL-7 (Interleukin 7) • IL-11(Interleukin 11)

  13. Cytokines in the Immune Response • Innate immune response • IL 1-(Macrophage)-fever, capillary effects • IL 6-(Macrophage)-adaptive immunity via B cells • IL 12(Macrophage)-adaptive immunity via T helper cells • TNF (Macrophage)-capillary effects, activates neutrophils • IFN alpha (Macrophage)-multiple effects • IFN beta (Fibroblasts)-multiple effects

  14. Cytokines in the Immune Response • Adaptive immune response • IL 2-(T cells)-multiple effects) • IL 4-(T cells & mast cells)-T cell differentiation, IgE production • TGF beta –(T cells, macrophages)-inhibits adaptive immune response • IFN gamma-(T cells, NK cells)-Macrophage activation

  15. Subsets of T helper Cells • T helper 1 • IgG production/Complement fixation • Macrophage activation • DTH • CTL production • T helper 2 • IgE production • Eosinophils

  16. Cytokine antagonism and viral diseases • Using cytokines therapeutically

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