Immunomodulation and Immunosuppression

Question 1

Immunomodulation

Answer 1

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

Question 2

Biologics- Immunomodulators

Answer 2

Products using molecular biologic techniques including recombinant DNA technology e.g. monoclonal antibodies, fusion proteins etc.

Question 3

An example of a biologic immunomodulator

Answer 3

anti-TNF (pro-inflammatory cytokine) e.g. infliximab, etanercept

Question 4

Passive immunisation is used for what infectious agents?

Answer 4

Hep B, botulism, VZV, antivenom

Question 5

Give 2 examples of immunostimulation

Answer 5

Pooled human immunoglobulin for antibody deficiencies
G-CSF/GM-CSF (colony stimulating factor) act on bone marrow to increase production of mature neutrophils e.g. neutropenic patients post chemo

Question 6

Give 6 effects of corticosteroid actions

Answer 6

Decrease neutrophil margination
Decrease production of pro-inflammatory cytokines
Inhibits phospholipase A2 (decreases production of arachidonic acid)
Lymphopenia
Decreased T cell proliferation-less likely to respond
Decreases immunoglobulin production

Question 7

Side effects of corticosteroids

Answer 7

Carbohydrate and lipid metabolism (diabetes, dyperlipidaemia)
Decreased protein synthesis-poor wound healing
Osteoporosis
Glaucoma and cateracts
Psychiatric complications

Question 8

Name 4 antimetabolites (T cell targeted immunosuppression)

Answer 8

Azathioprine
Mcophenolate Mofetil
Methotrexate
Cyclophosphamide

Question 9

Name 4 types of T cell targeted immunosuppression

Answer 9

Antimetabolites
Calcineurin Inhibitors
M-Tor Inhibitors
Biological DMARDs

Question 10

Mechanism of action of antimetabolites

Answer 10

Inhibit nucleotide purine synthesis-prevents early stages of activated cells proliferation-will target any rapidly dividing cell.
Azathioprine is a guanine anti-metabolite
Mycophenolate Mofetil prevents the production of guanosine triphosphate

Question 11

Side effects of azathioprine and mycophenolate mofetil

Answer 11

Hepatotoxicity/hepatitis
Anaemia
Bone marrow suppression

Question 12

Describe the mechanism of action of methotrexate and common side effect

Answer 12

Folate antagonist- pneumonitis

Question 13

Describe the mechanism of action of cyclophosphamide and common side effect

Answer 13

X link DNA- cystitis

Question 14

Mechanism of action of calcineurin inhibitors

Answer 14

Interfere with the initial T cell activation- prevent activation of NFAT-factors which stimulate cytokines i.e IL-2 and INF-y gene transcription. REVERSIBLE inhibition of T cell activation, proliferation and clonal expansion.

Question 15

What are 2 calcineurin inhibitors

Answer 15

Ciclosporin A

Tacrolimus

Question 16

Mechanism of action of ciclosporin A

Answer 16

Binds to intracellular protien cylophilin.

Question 17

Mechanisms of action of tacrolimus

Answer 17

Bind to intracellular protein FKBP-12

Question 18

Give an example of an M-Tor inhibitor

Answer 18

Sirolimus (rapmycin)
Macrolide antibiotic-also binds to FKBP12 but different effects-inhibits response to IL-2, causes cell-cycle arrest at G1-S phase in T cell.

Question 19

Calcineurim/M-TOR side effects

Answer 19

Hypertension
Nephrotoxicity
Hepatotoxicity
Hirsutism-excessive hair growth

Question 20

Name the 2 main groups of biological DMARDs

Answer 20

Anticytokines

Anti B cells

Question 21

Anticytokines- Anti TNF

Answer 21

TNF activates macrophages, Used in treatment of RA, Crohn’s, psoriasis, ankylosing spondylitis. Increases risk of TB

Question 22

Anti IL-6

Answer 22

Type of biological DMARD e.g. tocilizimab

Used in therapy of RA and AOSD (adult onset still’s disease)

Question 23

Anti IL-1

Answer 23

Used in treatment of AOSD and other autoimmune conditions

Question 24

Anti B cells

Answer 24

Rifuximab (rufus shakespeare -BNOC)
mAb against CD20 on B cell surface. Used for treatment of lymphomas, leukaemias, transplant rejection and autoimmune disorders. Only targets B cells in the blood, not in the bone marrow or lympphoid tissue.

Question 25

2 examples of adoptive immunotherapy

Answer 25

Bone marrow transplant

Stem cell transplant

Question 26

Describe 4 immunomodulators used for the treatment of allergies

Answer 26

Immune suppressants e.g. steroids
Allergen-specific immunotherapy
Anti-IgE monoclonal therapy
Anti-IL5 monoclonal treatment

Question 27

Mechanism of allergen specific immunotherap

Answer 27

Give a small amount of the allergen to switch off the immune response from Th2 (allergic) to Th1(non allergic) development of Treg cells and tolerance.

Question 28

mAB against IgE, used in the treatment of asthma, chronic urticaria and angioedema

Answer 28

Omalizumab