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

Principles of Immunology

Cytokines2/2/06

“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