Immunology 4b - Immune modulation 2

Question 1

MOA of corticosteroids

Answer 1

Inhibit phospholipase A2 thus reduce inflammation, effect on phagocytes, effect on lymphocytes

Question 2

Normal function of phospholipase A2?

Answer 2

This enzyme is involved in the conversion of phospholipids to arachidonic acid which is then converted to leukotrienes and prostaglandins by COX which are pro-inflammatory

Question 3

Effect of steroids on phagocytes

Answer 3

Decrease traffic of phagocytes in to inflamed tissue, reduce expression of adhesion on the endothelium + block signals that tell immune cells to move from blood in to tissue

Question 4

Which WCC marker is transiently affected by taking steroids?

Answer 4

Transient rise in neutrophil count

Question 5

Effect of steroids on lymphocytes

Answer 5

Lymphopenia by sequesteration of lymphocytes in lymphoid tisuse CD4 >CD8 >B cells
Blocks cytokine gene expression
Decreased antibody production
Promotes apoptosis

Question 6

SEs of corticosteroids (metabolic and others)

Answer 6

Metabolic: cushingoid features
Others: cataracts, glaucoma, peptic ulceration, pancreatitis
Immunosuppression

Question 7

Examples of anti-proliferative agents

Answer 7

Mycophenolate mofetil, azathioprine, cyclophosphamide

Question 8

Which antiproliferative agent affects B>T?

Answer 8

Cyclophosphamide

Question 9

MOA of antiproliferative agents

Answer 9

Inhibit DNA synthesis thus inhibit lymphocyte proliferation.

Question 10

MOA cyclophosphamide

Answer 10

Alkylating agent (alkylates guanine base of DNA)

Question 11

Indications for cyclophosphamide

Answer 11

COnnective tissue disease
Vasculitis e.g. SLE, Wegner’s
GvHD

Question 12

SE of cyclophosphamide

Answer 12

BM suppression
Haemorrhagic cystitis (toxic metabolite secreted in urine)
Malignancy - bladder cancer, non-melanoma skin cancer, haematological

Question 13

Azathioprine MOA

Answer 13

Purine analogue so blocks purine de no vo synthesis

T>B

Question 14

Indications of azathioprine

Answer 14

Transplantation
Autoinflammatory disease e.g. IBD
Autoimmune disease

Question 15

SE of azathioprine

Answer 15

Accumulation if have TPMT deficiency
Hepatotoxicity
Infection

Question 16

Mycophenolate MOA

Answer 16

Anti-metabolite, blocks de novo guanine synthesis

Question 17

Indications of mycophenolate

Answer 17

Transplantation (gold standard)

Autoimmune disease and vasculitis

Question 18

SE of mycophenolate

Answer 18

Infection - HSV reactivation and progressive multifocal leukoencephalopathy (JC virus)

Question 19

Indication for plasmapheresis

Answer 19

severe Type II hypersensitivity e.g. Goodpasture’s, myasthenia gravis, AB-mediated rejection

Question 20

Complications of plasmapheresis

Answer 20

Rebound antibody production therefore often given with an anti-proliferative agent, cyclophosphamide

Question 21

4 inhibitors of cell signalling

Answer 21

Calcineurin (tacrolimus, ciclosporin)
mTOR (sirolimus)
JAK (tofacitinib, ruxolitinib)
PDE4 (Apremilast)

Question 22

Calcineurin inhibitor MOA

Answer 22

Prevent T-cell signalling by blocking IL-2 production

Question 23

SE of both tacrolimus and ciclosporin

Answer 23

Nephrotoxic
HTN
Neurotoxic
Diabetogenic
Dysmorphic features

Question 24

Which of the two calcineurin inhibitors –> dysmorphic features more commonly?

Answer 24

CICLOSPORIN –> GUM HYPERTROPHY + HIRSUTISM

Question 25

JAK inhibitor MOA

Answer 25

Interferes with JAK-STAT signalling pathway thus reduces inflammatory molecules

Question 26

JAK inhibitor indications

Answer 26

RA or psoriatic arthritis

Question 27

PDE4 inhibitor indications

Answer 27

Psoriasis or psoriatic arthritis

Question 28

PDE4 inhibitor MOA

Answer 28

Increase cAMP –> activate PKA –> prevent activation of transcription factors –> reduced production of cytokines

Question 29

Agents targeted at T-CELL surface antigents

Answer 29

ABA
Anti-thymocyte globulin (ATG)
Basiliximab (anti-CD25/IL-2R alpha chain)
Abatacept (CTLA-4 Ig)

Question 30

Agent which prevents T cell migration

Answer 30

Natalizumab, targets a4b7 integrin

Question 31

ATG indication and effect

Answer 31

T-cell depletion

Useful in allograft rejection

Question 32

Basiliximab effect and indication

Answer 32

Inhibits T-cell proliferation

Prophylaxis of allograft rejection

Question 33

Abatacept effect and indication

Answer 33

RA
ctla-4 Ig infused protein, enhances the CTLA-4 checkpoint –> inhibits T cell activation
Opposite of ipilimumab

Question 34

What cells express CD20?

Answer 34

Mature B cells, nOT plasma cells

Question 35

SE of rituximab

Answer 35

Infection (PML) , HepB reactivation

Question 36

Indication of natalizumab and SE

Answer 36

Relapsing MS

SE: PML (JC virus)

Question 37

Which 3 agents increase PML risk

Answer 37

Mycophenolate
Rituximab
Natalizumab

Question 38

Tocilizumab target

Answer 38

IL-6 receptor

Question 39

Tocilizumab affects which immune cells?

Answer 39

Reduced activation of macrophages, T cells, B cells and neutrophils (LYMPHOID AND MYELOID CELLS)

Question 40

Tocilizumab indications

Answer 40

Castleman’s disease (IL-6 secreting tumour)

RA

Question 41

Which drug is not useful in IBD?

Answer 41

Etanercept (TNF decoy receptor)

Question 42

2 examples of anti-tNFa drugs

Answer 42

Infliximab, adalimumab

Question 43

Which agent directed at cytokines can be used to treat osteoporosis?

Answer 43

Denosumab

Question 44

Which cytokines shares the p40 subunit and which drug targets both these cytokines?

Answer 44

IL-12 and IL-23, targeted by ustekinumab (psoriatic arthritis, psoriasis)

Question 45

When is the peak of injection site reactions?

Answer 45

~48 hours or at site of old injections = recall reactions (not usually igE or immune complex mediated)