cytokines 1 Flashcards
signalling
initially cytokines interact with the high affinity receptor
leads to heterodimeric complex - low affinity receptir is recruited leading to the phosphorylation of jak
jak phosphos the cytoplasmic tail of the receptor creating a docking site
docking site allows the recruitment of STAT that can be phospho by jak
cytokine families
type 1
short chain cytokines
long chain cytokines
type 2
type1 IFNs
type 2 IFNs
chemokine fam
tumour necrosis fam
IL-2
belongs to common y chain family of cytokines
produced by t cells and dendritic cells
receptor expressed by t b and nks
fine tunes immune response
activates stat 5 - regulates other t subsets and promotes treg prolif and survival
promotes t helpers, t regs, ts, bs, monocytes and nk cells
antigen present ing cell binds to resting t cells
il-2 ar eproduced and activate t cell
il a, b and y bind il2 leading to clonal expansion and differentiation of effector t cells
il-4
produced by t cells, esionphils, nk cells and mast cells
receptor expressed by t b nk mast cells and basophils
activates stat 6 and regulates th2 cells
activates stat 3 via jak1/stat3 kinases
il4 binds high affinity il4a and recruits low affinity common y chain to trigger signalling
il4 deregulation contributes to the development of allergies and asthma
il4 type 1 receptor
il4ra, il4, y chain
signals to hematopoeitic cells, iadaptive immunity and t/b regulation
il4 type 2 receptor
il4ra, il4, il13ra1
non hematopoeitic cells, innate immunity, effector function
il-6
signalling compelx formed by 2 il6, 2 il6ra and 2 gp130
during inflam transmembrane domain of il6ra can be cut off - leads to soluble form of il6ra that upon binding to il6 can signal in every cell type
can have pro or anti inflam functions
deregulation leads to chronic inflam - eg inflam bowel disease
pro-inflam activities of il6
expansion and activation of t cells
diff of b cells
regualtion of acute phase response
anti-inflam activities of il6
metabolic control
il6 dependent regeneration
bone metabolism
pain
gp130
a common y chain shared by many cytokines
il6 activation
fiirst binds high affinity to il6ra
2nd heterodimeric complex formed and signalling occurs
cytokines sites that interact with receptor
site 1 - interface
high affinity interface
hot spots
very specific
site 2 - interface
low affinity
less specific
surface complementarity
stem contact
only in some complexes
helps stabilise the cytokine-cytokine receptor complex
