Immunosuppressants

Question 1

Describe the activation and the role of interleukin 2

Answer 1

Released by T helper cells, once the T cells recognise a threat. The IL 2 goes on to activate and increase proliferation of B and T cells

Question 2

Describe function of B cells

Answer 2

Mature in the bone marrow
Once stimulated, B cells turn into plasma cells which produce antibodies to destroy an antigen

Question 3

NK cells and phagocytes are involved in which branch of the immune system?

Answer 3

Innate

Question 4

Are T and B cells part of the innate or adaptive immune system?

Answer 4

Adaptive
T and B cells are lymphocytes

Question 5

How does the immune system prevent cancer

Answer 5

Monitors our own cells for abnormal proliferation

Question 6

Which cell type is primarily involved in transplant rejection

Answer 6

T cells

Question 7

With transplants, the donor and recipient must be well matched for which molecule?

Answer 7

HLA (human leukocyte antigens)

Question 8

Name 2 calcineurin inhibitors

Answer 8

Cyclosporin and tacrolimus

Question 9

Explain the action of calcineurin inhibitors

Answer 9

Calcineurin typically promotes the dephosphorylation of NFAT, which then translocates to the nucleus to initiate IL2 transcription following T helper cell activation.
- the inhibitors form complexes with proteins in the cascade, which then complexes with calcineurin to prevent its action

Question 10

Do cyclosporin and tacrolimus effect B or T cells?

Answer 10

T cells

Question 11

Why should cyclosporin inhibitors be commenced prior to transplant

Answer 11

They prevent the production of new immune memory, but do not wipe out old memory

Question 12

Tacrolimus ADRs?

Answer 12

Nephrotoxicity, hypertension, hyperlipidaemia

Question 13

Name 3 anti-proliferative drugs

Answer 13

Rapamycin, azathioprine (6-mercaptopurine), mycophenolate mofetil

Question 14

Which anti-proliferation drug forms a complex with FKBP12 to inhibit ToR signalling, which prevents progression from G1 to S phase of the cell cycle?

Answer 14

Rapamycin

Question 15

Name some side effects of all the anti-proliferative drugs

Answer 15

Given that these are cytotoxic and affect all rapidly dividing cells, has lots of ADRs
-leukopenia, anaemia, increased risk of infection, reduced wound healing, alopecia, nausea, vomiting

Question 16

Which class are cytotoxic, anti-proliferative or calcineurin inhibitors?

Answer 16

Anti-proliferative

Question 17

Azathioprine is a prodrug for which active metabolite?

Answer 17

6-mercaptopurine

Question 18

Action of 6-mercaptopurine?

Answer 18

Mimics purines (guanine and adenine) and blocks the metabolism of purines to prevent DNA synthesis. Prevents the proliferation of B and T cells

Question 19

Explain the action of mycophenolate mofetil

Answer 19

Blocks the enzyme inosine monophosphate dehydrogenase, which is needed to de novo purine synthesis. This prevents the synthesis of DNA

Question 20

Which MAB blocks TNF-alpha

Answer 20

Infliximab

Question 21

Role of TNF-alpha?

Answer 21

Amplifies the immune response by activating fibroblasts and inflammatory cytokines

Question 22

Anti-IL2 receptor antibodies bind to the IL2 receptor and prevent its activation, causing the death of IL 2 dependent cells. Name 2 of these drugs

Answer 22

Basiliximab and daclizumab

Question 23

Side effects of MABs?

Answer 23

Headache, GI effects, fatigue, itch, etc

Question 24

Explain the immunosuppressive effects of glucocorticoids

Answer 24

The bind to an intracellular receptor to reduce the gene expression of pro-inflammatory molecules. Also inhibits IL2 and T helper cell proliferation