cytokines Flashcards
What are cytokines and how they work
small proteins that modulate the activity of WBC
mainly work by binding to tyrosine kinase receptors and cause alteration in gene expression
Give examples of cytokines
interleukins, chemokine, TNFa, interferons , CSFs
cytokine levels in the blood
very low levels that only increase during inflammation
what are cytokines involved in
- growth factors
- differentiation= causes the precursor of WBC to divide then differentiate into specific WBC
- chemotaxis
- production of antibodies
release + action of cytokines
they are released by macrophages
- can act autrocrine- on the cell that released it e.g. TNFa or paracrine on neighbouring cells
JAK-STAT pathway
- cytokine binds on homodimer cytokine receptor which is associated with tyrosine kinase called JAK
- binding of cytokine causer dimerisation of receptor this activates JAK
- JAK then phosphorylates tyrosine on the intracellular domain of cytokinereceptor
- this phosphorylated tyrosines attracts 2 STAT to bind
- STAT binds and its phosphorylated by JAK causes it dissociate
- STAT dissociates and dimerise makes a complex that enters nucleus acts as a transcription factor binds to a specific gene sequence + promote transcription
what cytokine use JAK- STAT pathway
interferons, interleukins, CSF
this is main pathway
how TNF functions in normal and cancer cells
- normal cells= TNF mitogenic promotes mitosis
- cancer cells= TNF promotes cell death
TNF signalling pathway in inflammation
excess TNF causes proinflammatory cells to be produced
TNF binds to TNFRI receptor this causes phosphorylation of cytosol complex called IKB/NFKB
IKB dissociates and degraded
NFKB is left which enters nucleus and acts to acts as an enhancer to switch on pro-inflammatory genes
not all chemokine are pro-inflammatory give 2 examples of anti-flammatroty cytokine AND their function
IL-4 and TGF Beta
- produces antibodies to reduce inflammation involved in priming (growth + differentiations of b-cells)
- inhibit chemokine
- inbit TH1
2 types of cells made by T-cell CD4 prescursor
TH1 and TH2 these are 2 types of helper t cells
TH1 pathway
- these are pro inflammatory they activate macrophages
- release IL-2 this has positive feedback allows more TH1 to be made
- release IFNg this suppresses TH2 production
TH2 pathway
- anti inflammatory cells that develop into antibodies
- produce IL4 this allows more TH2 production and inhibits TH1 production
TGF B also inhibit TH1 production
example of pro inflammatory cytokines and function
- TNF, IL-1, IL-6
- increase COX2 activity this increases PGE2 this increase temp, vascular permeability
- acts on liver increase CRP
- induces CSF release from macrophages + endothelial cells these act on bone marrow increase WBC production allows WBC to be replenished.
- increase expression of cell adhesion molecules
- TNF= increases MMP that attack bone cartilage causes issues in RA
- TNF= promotes fibroblast proliferation = seal off inflamed areas promotes scarring–> loss function
- TNF promotes iNOS= increase NO= vaso dilation
pro inflammatory cytokine link to inflammation
redness - TNF –> increase NO–> vasodilation
swelling –> increase PGE vasodilation
heat –> IL-1 increase PGE in hypothalamus
loss of function –> TNF activates fibroblast proliferation
pain–> increase PGE sensitises to bradykinin
