Cytokines Flashcards
cytokines act through cell-surface protein receptors which trigger signaling pathways typically activated through _____
protein phosphorylation, leading to activation of specific transcription factors
explain how cytokines are pleiotropic, redundant, and potent
pleiotropic: 1 cytokine can have multiple and different effects on the same cell and on many cell types (may depend on exposure time or concentration)
redundant: difference cytokines can have same or overlapping effects
potent: present in small concentrations, so receptors have very high affinity for their cytokine
cytokines vs chemokines (functions and signaling)
cytokines: small soluble proteins (can be filtered out by kidney), signal to receptors coupled to protein kinases, stimulate growth/differentiation/immunity
chemokines: smaller, signal through GPCR, chemotactic and cellular activation, cell trafficking
identify each as a characteristic of either cytokines or chemokines:
a. signal through protein kinases
b. signal through GPCR
c. stimulate growth, differentiation, defensive capacity of immune system
d. chemotactic, cellular trafficking
cytokines:
a. signal through protein kinases
c. stimulate growth, differentiation, defensive capacity
chemokines:
b. signal through GPCR
d. chemotactic, cellular trafficking
what do IL-1 and TNF-alpha do
cause inflammation
what role do IL-2 and IFN-alpha/beta/gamma have?
- T-cell growth and division
- viral defense
- cell-mediated immunity
effect of IL-8
chemotaxis
function of TGF-alpha vs TGF-beta
TGF-alpha: inflammation
TGF-beta: downregulation of immune response, regulation of embryonic development
Type I cytokine (hemopoietin) receptors (IL-2-7, IL-9) and Type II cytokine receptors (IFN-a/b, IFN-y, IL-10) signaling through _____ pathway
JAK-STAT signaling:
1. cytokine mediated receptor dimerization
2. JAK-mediated phosphorylation of receptor chains
3. recruitment of STAT to cytokine receptor
4. JAK-mediated phosphorylation/dimerization of STAT
5. STAT translocation to nucleus —> transcription
*depending on what JAK/STAT combination you have, different genes transcribed
describe JAK-STAT signaling in cytokine receptors (Type I and II cytokine receptors)
JAK-STAT signaling:
1. cytokine mediated receptor dimerization
2. JAK-mediated phosphorylation of receptor chains
3. recruitment of STAT to cytokine receptor
4. JAK-mediated phosphorylation/dimerization of STAT
5. STAT translocation to nucleus —> transcription
*depending on what JAK/STAT combination you have, different genes transcribed
match the cytokine receptor component with the cytokines it binds:
TRAF, IRAK, G proteins,
TNF-a/b, FasL, IL-1, chemokines
TNF-a/b and FasL act through TNF receptor family which utilizes TRAF
IL-1 acts through IL-1 receptor family which utilizes IRAK
chemokines act through GPCR which utilize G proteins
what is the negative consequence of cytokine receptors having conserved regions in their chains?
mutation in conserved region effects interaction with many different cytokines —> many effects
example:
- X-SCID: mutation in gamma chain, blocks T cell and NK (but normal B cells)
- Steve-Wiedemann-like Syndorme: mutations in gp130 (component of IL-6 receptor family), lethal disease
how does mutation in cytokine receptors cause X-SCID and lethal Stuve-Wiedemann-like syndrome?
- X-SCID: mutation in gamma chain, blocks T cell and NK (but normal B cells)
- Steve-Wiedemann-like Syndorme: mutations in gp130 (component of IL-6 receptor family), lethal disease
*consequence of conserved regions of cytokine receptors is that binding of many cytokines is affected and therefore many downstream effects
IFN-alpha and IFN-beta vs IFN-lambda (what family of interferons do they belong to, what is their role)
IFNa/b: Type I IFNs, act on most nucleated cells
IFN-lambda: Type III IFN, act only on epithelial cells on mucosal surfaces, respiratory tract, gut, reproductive system (targeted protection for cells often exposed to viral entry)
*both types induce antiviral state, and both types signal through Type II cytokine receptors (JAK-STAT)
interferons are sometimes used as therapeutics.
what type of IFN is used to treat HBV, HCV, and papillomavirus?
IFN-alpha
