CE L3.2 Therapies continued Flashcards
Patients with RA have high/low circulating levels of IL1β?
High
IL1β causes RA symptoms by inducing ……. and …….
PGs and collagenases
To block TNF you need high doses because ………..
TNF binds to trimeric receptors - you need high levels to ensure maximum blockage
TNF is found where in the cell?
membrane associated
Is TNF a
homotrimer
OR
heterotrimer?
homotrimer
TNF is part of ………………………… of cytokines.
Includes TNFα, TNFβm Fas-L and CD40
superfamily
Bac, viruses TNF, IL-1 and IL-2 all increase ………… but not necessarily …………………..
mRNA
but not necessarily protein
……………………… increases the stabilisation of mRNA during TNF production
LPS
TNF is synthesised as ………………………………………..
non-glycosylated membrane bound protein
What cleaves TNF from the membrane?
MMPs
Both membrane bound and soluble forms of TNF are active and mediate ………… and ………. effects
inflammatory and cytotoxic effects
through cell-cell contact
TNF receptors may be membrane bound or soluble (cleaved by ……………………….)
MMP
Two types of TNF receptors and their fucntions
TFNRI - apoptosis (recruits caspases) and gene transcription (TRAFs)
TNFRII - gene transcription (recruits TRAFs)
TNF receptors are basically a molecular switch to determine:
death or activation
How does TNF engage the receptor?
Homotrimerises
-3 chains polymerise to form triangle and C termini engage 3 receptors
