Flashcards in 48-Cytokines Deck (44)
1
What is a cytokine?
proteins released by cells that participate in the immune response
2
How is cytokine expressed?
released extracellularly or expressed on surface of the cell
3
How are cytokines recognized?
unique receptors in surface of immune cells. activation of receptor results in changes in the function
4
what are the functions of cytokines in the immune response?
hematopoiesis
chemotaxis
inflammation
antiviral response (interferons)
immune cell activation
suppression
5
how do cytokines act?
autocrine, paracrine, endocrine
6
what is pleiotropy?
a single cytokine has more than 1 function depending on the cell it targets
B cell-activation, proliferation, differentiation
thymocyte-proliferation
mast cell-proliferation
7
what is redundancy?
cytokines have the same action
IL2, 4, 5 do proliferation
8
what is synergy?
cytokines act together for a response
IL4 and 5 induce class switch to IgE
9
what is antagonism?
cytokines inhibit one another
Il4 and IFNy block class switch to IgE
10
How is a cell fate decided?
cells integrate signals from many cytokines
11
what are the phases of sepsis?
cytokine storm and immune suppression?
12
what is the cytokine storm?
1st phase in sepsis, driven by release of inflammatory cytokines
13
what is the immune suppression in sepsis?
2nd phase, days to weeks after onset, immunosuppressive cytokines released. this phase is resolved with elimination of infection or death
14
cytokine treatments for sepsis
most have failed. have not shown and increase in survival and have worsened death
15
what are the 7 cytokine families
growth factory family
TGF-B
IL-1
TNF
IL-17
chemokine
classical
16
how are the cytokine families delineated
by their receptor which have distinct signaling pathway. signaling pathway defines the treatment for cytokine
17
Growth factor family receptor
tyrosine kinase domains
18
growth factor family action
increased tyrosine phosphorylation signaling, immune cell differentiation
19
TGF-B receptor
serine/threonine kinase domains, tetramerization of 2 type 1 and 2 type 2 for phosphorylation of SMAD proteins
20
TGF-B action
inhibit immune cell function, t cell differentiation, antibody production, promote tissue repair
21
IL-1 Family receptor
TIR domain, binding of MyD88
22
IL-1 family action
MyD88 induces downstream signaling to activation NF-kB for inflammation
23
What does IL-1Ra do?
inhibit IL-1
24
TNF family receptor
TRAF and TRADD
25
TNF family action
TRAF is inflammatory
TRADD does apoptosis
26
What does TNF alpha and TNFR1 (receptor) do?
part of TNF family that can be inflammatory or do apoptosis
27
IL-17 Family receptor
TLR and TNF
28
IL-17 family action
dimerization and bind ACT1 which interacts with TRAF for inflammation
29
Chemokine family receptor
7 transmembrane g protein coupled receptor
30
chemokine family action
activation of small molecular weight g proteins, chemotaxis (migration of immune cells)
31
what are the functions of chemokine receptors
inflammatory: movement towards infection
homeostatic: movement before an infection during homeostasis
atypical: silent and act as negative regulators
viral: allow pathogens to modulate immune responses
32
Classical cytokine family receptor
JAK/STAT, heterodimeric or trimeric
33
Classical cytokine family action
activation of JAK kinases to phosphorylate STAT, lots of functions
34
Type I Cytokine
Hemopoietin, conserved structural elements
Conserved cysteines, conserved WSXWS, conserved y, conserved B, conserved gp130
differentiation, homeostasis, activation, suppression
35
Type II Cytokine
Interferon
conserved cysteines, use distinct pools of JAK and STAT
antiviral responses
36
Three main classes of drugs targeting cytokine function
actual cytokine: EPO
antibody inhibitors of cytokines (anti-TNF)
small molecule drugs (anti-JAK kinase)
37
How do recombinant cytokines work
15 recombinations
enhance immune function (interferon a, b, y, epo, il-2, il-11, G-CSF, GM-CSF)
38
what is the exception to recombinant cytokines?
anakinra
39
how does anakinra work?
IL-1Ra which inhibits IL-1
40
what is the problem with recombinant cytokines
very powerful and substantial side effects
41
how do antibodies targeting cytokines work?
treat rheumatic disease, target IL-6, Blys, TNF-a, interferon-a
42
what is the problem is antibody cytokine drugs?
increased infection, expensive, not as dangerous because of redundancy and low level activation
43
how do small molecule inhibitors work?
inhibit JAK/STAT
44