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  High affinity for receptors  Active in picomole amounts

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

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

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

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

Cytokine-generating Cells  Innate immunity Macrophages Endothelial cells Fibroblasts  Adaptive immunity T lymphocytes Macrophages NK cells

Cytokine Receptors  Ig super family  Class I- hematopoietin  Class II-interferon  TNF  Chemokine

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

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

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)

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

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

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

 Cytokine antagonism and viral diseases  Using cytokines therapeutically