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Cytokines: Key Signaling Molecules in Immunology

Explore the diverse family of cytokines, from their chemical structure to their role in immune responses, and their impact on cell communication. Learn about cytokine receptors, signal transduction, hematopoiesis, and their involvement in viral diseases. Discover how cytokines regulate innate and adaptive immunity.

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Cytokines: Key Signaling Molecules in Immunology

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  1. Principles of ImmunologyCytokines

  2. Cytokines (Greek cyto-, cell; and -kinos, movement) are small cell-signaling proteinmoleculesthat are secreted by the cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication. Cytokines can be classified as proteins, peptides, or glycoproteins; the term "cytokine" encompasses a large and diverse family of regulators produced throughout the body by cells of diverse embryological origin.

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

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

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

  6. Names of Cytokines • Source • e.g.,Lymphokines(secreted by lymphocyte) • Function • e.g.,Chemokines(low molecular weight) • Intercellular action • e.g., Interleukins(secreted by leukocyte)

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

  8. 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

  9. Redundancy

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

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

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

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

  14. 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)

  15. 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

  16. 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

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

  18. Cytokine antagonism and viral diseases • Using cytokines therapeutically

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