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Principles of Immunology Cytokines 2/2/06 “Live simply so others can simply live.” Anonymous
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Word List Autocrine Endocrine Immunoglobulin superfamily Interleukin Paracrine Pleiotropy Stem cell factor
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Chemical Structure Low molecular weight proteins, <30kD High affinity for receptors Active in picomole amounts
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Chain of Cytokine Action Stimulus>Cytokine-producing cell> Cytokine>Target cell>Receptor> Biological effect(s)
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Names of Cytokines Source e.g.,Lymphokines Function e.g.,Chemokines Intercellular action e.g., Interleukins
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Action of Cytokines Autocrine Affects the generating cell (self) Paracrine Affects cells in the immediate vicinity Endocrine Affects cells remote from the secreting cell
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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
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Cytokine-generating Cells Innate immunity Macrophages Endothelial cells Fibroblasts Adaptive immunity T lymphocytes Macrophages NK cells
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Cytokine Receptors Ig super family Class I- hematopoietin Class II-interferon TNF Chemokine
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Cytokine Receptors Multimeric receptors Common signal-transducing subunits Unique high affinity subunits High affinity subunits associated with activation of target cell
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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
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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)
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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
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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
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Subsets of T helper Cells T helper 1 IgG production/Complement fixation Macrophage activation DTH CTL production T helper 2 IgE production Eosinophils
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Cytokine antagonism and viral diseases Using cytokines therapeutically
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