Principles of Immunology

Cytokines
2/2/06

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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 cells 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