12 Immunotherapeutics

Question 1

Define immunomodulation.

Answer 1

Manipulating the immune system using immunomodulatory drugs to achieve the desired response.

Question 2

What are the three types of immunopotentiation?

Answer 2

Immunisation.
Replacement therapies.
Immune stimulants.

Question 3

What are the types, and risks of passive immunisation?

Answer 3

Pooled specific human immunoglobulin.vAnimal sera (antitoxins as antivenins).
Risk of viral transmission and serum sickness.

Question 4

Why are adjuvants needed in active immunisation?

Answer 4

Stimulates the desired immune response type e.g. predominantly antibody vs cytokine response.

Question 5

Name 5 therapies using immune stimulation

Answer 5

G-CSF/GM-CSF - neutrophil production
IL-2: stimulates T cell activation.
α-interferon: Hep C
β-interferon: MS therapy.
γ-interferon: CGD, atypical mycobacteria infection.

Question 6

How do corticosteroids work? (6)

Answer 6

Less neutrophil margination.
Less cytokines produced.
Inhibition of phospholipase A2 (less arachidonic acid derivatives.
Lymphopenia.
Decreased T cell proliferation.
Reduced immunoglobulin production.

Question 7

Side effects of corticosteroids. (6)

Answer 7

Diabetes and hyperlipidaemia.
Poor wound healing.
Osteoporosis.
Glaucoma and cataracts.
Psychiatric complications.

Question 8

What are the 4 types of lymphocyte targeting drugs?

Answer 8

Antimetabolites/ cytotoxics.
Calcineurin inhibitors.
M-TOR inhibitors.
IL-2 receptor mABs.

Question 9

Name two calcineurin inhibitors. How do they work?

Answer 9

Ciclosporin A (CyA) - binds to cyclophilin.
Tacrolimus (FK506) - binds to FKBP-12.
Prevents NFAT activation (cytokine gene transcription). Inhibit T cell activation, proliferation and expansion.

Question 10

Name an M-TOR inhibitor.
How does it work?
When is it used?

Answer 10

Sirolimus (rapamycin).
Binds to FKBP12, inhibits IL-2 response. Arrests T cell cycle at G1-S phase.
Transplantation and AI diseases.

Question 11

Name 4 cytotoxics/ antimetabolites. How do they work?

Answer 11

Azathioprine (AZA) - guanine anti-metabolite.
Mycophenolate mofetil (MMF) - inhibits IMPDH.
Methotrexate (MTX) - folate.
Cyclophosphamide - cross links DNA.
Impact DNA production, prevents proliferation of B and T cells

Question 12

What are the side effects of cytotoxics/antimetabolites? (4).
Cyclophosphamide specifically?
MTC?

Answer 12

Bone marrow suppression, gastric upset, hepatitis, infection susceptibility.
Cyclophosphamide - cystitis.
MTC - pneumonitis.

Question 13

What are the uses of AZA/MMF (cytotoxics)? (2).

Answer 13

Autoimmune diseases.

Allograft rejection.

Question 14

What are the uses of methotrexate (cytotoxic)? (5).

Answer 14

Rheumatoid arthritis.
Psoriatic Arthritis.
Polymyositis.
Vasculitis.
Graft vs host disease in bone marrow transplant.

Question 15

What are the uses of cyclophosphamide (cytotoxic)? (2).

Answer 15

Vasculitis.

SLE.

Question 16

Name two examples of IL-2 receptor monoclonal antibodies.

Answer 16

Basiliximab.

Daclizumab.

Question 17

What are DMARDs used for?

Answer 17

Disease-modifying anti rheumatic drugs.

Rheumatoid Arthritis.

Question 18

Which anti-cytokines are used as DMARDs? Risks?

Answer 18

Anti TNF. TB risk.
Anti-IL-6 (tocilizumab). Serum lipid control risk.
Anti-IL-1 (anakinra, rilonacept, canakinumab).

Question 19

How does Rituximab function?

What is it used for? (4).

Answer 19

Chimeric mAb against CD20 on the B cell surface. This kills all cells with autoantibody and allows repopulation.
Lymphomas, leukaemias, transplant population, autoimmune disorders.

Question 20

Name two types of adoptive immunotherapy.

Answer 20

Bone marrow transplant.

Stem cell transplant.

Question 21

What types of immunomodulators are used in allergy? (4).

Answer 21

Immune suppressants.
Allergen specific immunotherapy.
Anti-IgE monoclonal therapy.
Ant-IL-5 monoclonal treatment.

Question 22

When is allergen specific immunotherapy indicated?

How does it work? (2).

Answer 22

Uncontrollable allergic rhinoconjuctivis.
Anaphylaxis to insect venoms.

Switches response from Th2 to Th1. Development of Treg cells and tolerance.

Question 23

What is omalizumab?
Rx for? (3)
Possible side effect?

Answer 23

mAb against IgE.
Rx for asthma, chronic urticaria and angiodema.
Severe systemic anaphylaxis.

Question 24

What is mepolizumab
What does it do?
When is it used?

Answer 24

mAb against IL-5.
Prevents eosinophil recruitment and activation.
Asthma (limited effect).