Cytokines Principles of Immunology 2/2/06 “Live simply so others can simply live.”

Principles of Immunology
Cytokines
2/2/06
“Live simply so others can simply live.”
Anonymous
Word List
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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
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Ig super family
Class I- hematopoietin
Class II-interferon
TNF
Chemokine
Cytokine Receptors
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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
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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)
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
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IgG production/Complement fixation
Macrophage activation
DTH
CTL production
 T helper 2
 IgE production
 Eosinophils
 Cytokine antagonism and viral
diseases
 Using cytokines therapeutically