Christine Edmead

Question 1

What are the effects of cytokines?

Answer 1

1. induces T and B cell differentiation
2. Activation of macrophages
3. Cellular migration (chemokines)
4. Apoptosis (TNF and FasL)

Question 2

What cytokines do TH2 cells release?

Answer 2

TH2 releases anti-inflammatory cytokines IL-10, IL-11 and IL-4

Question 3

Chronic inflammation is largely driven by what cytokines?

Answer 3

TNF and IL-1

Question 4

What is the first line treatment of RA?

Answer 4

NSAIDS

Question 5

What is the second line treatment for RA?

Answer 5

DMARDS

generally monotherapy

Question 6

Why aren’t combination therapies of DMARDs recommended in RA?

Answer 6

Only have a limited no. of options, combinations will use these up quickly
Generally have no synergistic response

Question 7

What is methotrexate?

Answer 7

Folate antagonist, antiproliferative effect via inhibition of dihydrofolate reductase

Question 8

What does of methotrexate should be given in RA?

Answer 8

7.5mg-15mg/week

Question 9

What are the side effects of methotrexate?

Answer 9

Depression of bone marrow and GI tract damage

Question 10

What are the side effects of penicillamine?

Answer 10

Side effects in 40% of patients. Taste disturbances, rashes, thrombocytopenia, autoimmune disease

Question 11

What is the general MOA of DMARDs?

Answer 11

Inhibit macrophage activation
Inhibit cell proliferation
Decrease the release of proinflammatory cytokines and ROS

Question 12

Where are endogenous corticoids released from?

Answer 12

Adrenal cortex

Question 13

Mineral corticoids affect what?

Answer 13

Water-electrolyte balance

Question 14

Addisons is caused by what?

Answer 14

Deficiency in glucocorticoid

Question 15

Cushings syndrome is caused by what?

Answer 15

Excessive glucocorticoid

Question 16

Conns syndrome is caused by what?

Answer 16

Excessive mineralcorticoid

Question 17

What is the MOA of glucocorticoids?

Answer 17

Glucocorticoids enter cells and bind to cytoplasmic receptors
This complex translocated to the nucleus to act as a transcription factor
Binds to response elements and activates gene transcription
Can interact and inhibit binding of other transcription factors (AP-1, NFKB)

Question 18

What are the metabolic side effects of steroids?

Answer 18

Osteoporosis - decrease collagen synthesis, osteoblast functions, Cas absorption
Diabetogenic plus increase in appetite
Mineralcorticoid effects - water retention, hypertension, oedema, and CV events.

Question 19

What are the two forms of IL-1 and the difference between them?

Answer 19

Il-1 alpha - mainly cystolic or membrane bound

IL-1 beta - most common circulating form

Question 20

Where is IL-1 synthesised?

Answer 20

Microtubules of monocytes/macrophages

Question 21

How is IL-1 activated?

Answer 21

IL-1 is synthesised as a precursor in microtubules. CD40L activates ICEC in EC and SM cells. Cleaved by ICE (IL-1 converting enzyme), which is also known as capsases. This release is facilitated by ATP acting on receptor P2X7.

Question 22

What are the effects of IL-1?

Answer 22

High concentration enters the blood and causes fever
Increased synthesis of COX-2 and iNOS
Increased expression of VCAM and ICAM
Increased bone erosion
Doesn’t induce apoptosis and septic shock

Question 23

What is the MOA of Enlionamab?

Answer 23

Anti-Icam

Blocks cellular adhesion molecules with an ab so T cells cannot migrate into the tissue

Question 24

What kind of immunotherapy is infliximab?

Answer 24

Chimeric ab

Question 25

What kind of immunotherapy is Humira?

Answer 25

Fully humanised ab