CE L3.2 Therapies continued

Question 1

Patients with RA have high/low circulating levels of IL1β?

Answer 1

High

Question 2

IL1β causes RA symptoms by inducing ……. and …….

Answer 2

PGs and collagenases

Question 3

To block TNF you need high doses because ………..

Answer 3

TNF binds to trimeric receptors - you need high levels to ensure maximum blockage

Question 4

TNF is found where in the cell?

Answer 4

membrane associated

Question 5

Is TNF a
homotrimer
OR
heterotrimer?

Answer 5

homotrimer

Question 6

TNF is part of ………………………… of cytokines.

Includes TNFα, TNFβm Fas-L and CD40

Answer 6

superfamily

Question 7

Bac, viruses TNF, IL-1 and IL-2 all increase ………… but not necessarily …………………..

Answer 7

mRNA

but not necessarily protein

Question 8

……………………… increases the stabilisation of mRNA during TNF production

Answer 8

LPS

Question 9

TNF is synthesised as ………………………………………..

Answer 9

non-glycosylated membrane bound protein

Question 10

What cleaves TNF from the membrane?

Answer 10

MMPs

Question 11

Both membrane bound and soluble forms of TNF are active and mediate ………… and ………. effects

Answer 11

inflammatory and cytotoxic effects

through cell-cell contact

Question 12

TNF receptors may be membrane bound or soluble (cleaved by ……………………….)

Answer 12

MMP

Question 13

Two types of TNF receptors and their fucntions

Answer 13

TFNRI - apoptosis (recruits caspases) and gene transcription (TRAFs)
TNFRII - gene transcription (recruits TRAFs)

Question 14

TNF receptors are basically a molecular switch to determine:

Answer 14

death or activation

Question 15

How does TNF engage the receptor?

Answer 15

Homotrimerises

-3 chains polymerise to form triangle and C termini engage 3 receptors

Question 16

When we target TNF we mainly target soluble OR membrane bound form?

Answer 16

Soluble

Question 17

Where does TNF act to cause fever?

Answer 17

hypothalamus

Question 18

Prolonged TNF exposure causes (2)

Answer 18

muscle wasting

septic shock

Question 19

What is TNF’s effect on hepatocytes

Answer 19

increased release of APP

Question 20

What is TNF’s effect on EC

Answer 20

induces expression of cytokines and adhesion molecules (from macrophages)

Question 21

ACUTE controlled release of TNF is good,

PROLONGED is bad

Answer 21

.