Immunotherapeutics

Question 1

Define immunomodulation

Answer 1

the act of manipulating the immune system using immunomodulatory drugs to achieve the desired immune response

Question 2

What therapeutic effects may immunomodulation have? (3)

Answer 2

immunopotentiation, immunosuppression or induction of immunological tolerance

Question 3

What are the mechanisms of immunomodulation? (7)

Answer 3

• immunisation
• replacement therapy
• immune stimulants
• immune suppressants
• anti-inflammatory agents
• allergen immunotherapy
• adoptive immunotherapy

Question 4

Define biologics

Answer 4

medical products produced using molecular biology techniques including recombinant DNA technology

Question 5

Name three methods of immunopotentiation

Answer 5

immunisation, replacement therapies, immune stimulants

Question 6

Define passive immunisation

Answer 6

transfer of specific, high-titre antibody from donor to recipient (provides but transient protection)

Question 7

What are the problems with passive immunisation?

Answer 7

risk of transmission of viruses and serum sickness

Question 8

What are the two main types of passive immunisation?

Answer 8

• pooled specific human immunoglobulin

- animal sera

Question 9

What are the main uses of passive immunisation?

Answer 9

• hep B prophylaxis treatment

- botulism, VZV, diptheria, snake bites

Question 10

Define active immunisation

Answer 10

to stimulate the development of a protective immune response and immunological memory

Question 11

What immunological materials can be used for active immunisation?

Answer 11

• weakened forms of pathogen
• killed inactivated pathogens
• purified materials (proteins, DNA)
• adjuvants

Question 12

What are the problems with active immunisation?

Answer 12

• allergy to components in vaccine
• limited usefulness in immunocompromised
• delay in achieving protection

Question 13

Is alpha-, beta- or gamma- interferon used in treatment of hep C?

Answer 13

alpha-interferon

Question 14

Is alpha-, beta- or gamma- interferon used in therapy of MS?

Answer 14

beta-interferon

Question 15

What are the 5 main groups of drugs used for immunosuppression?

Answer 15

• corticosteroids
• cytotoxic agents
• anti-proliferative/activation agents
• DMARDs
• biologic DMARDs

Question 16

What effect do corticosteroids have on neutrophil margination?

Answer 16

decrease it

Question 17

What effect do corticosteroids have on inflammatory cytokines?

Answer 17

reduce production of them

Question 18

What are the main side-effects of corticosteroids?

Answer 18

• carbo and lipid metabolism
• reduced protein synthesis
• osteoporosis
• glaucoma and cataracts
• psychiatric complications

Question 19

What are the main uses of corticosteroids?

Answer 19

• autoimmune diseases
• inflammatory
• malignancies
• allograft rejection

Question 20

What do the following group of drugs all target?:

anitmetabolites, M-TOR inhibitors, calcineurin inhibitors, IL-2 receptor mABs

Answer 20

lymphocytes

Question 21

How does ciclosporin A work?

Answer 21

calcineurin inhibitor - binds to intracellular protein cycophilin

Question 22

How does tacrolimus work?

Answer 22

calcineurin inhibitor - binds to intracellular protein FKBP-12

Question 23

What drug is also known as FK506?

Answer 23

tacrolimus

Question 24

What is the mode of action of calcineurin inhibitors?

Answer 24

prevents activation of NFAT

Question 25

How do calcineurin inhibitors effect T cells?

Answer 25

reversible inhibition of T cell activation, proliferation and clonal expansion

Question 26

What is the mode of action of sirolimus?

Answer 26

inhibits response to IL-2

Question 27

What effect does sirolimus have on T cells?

Answer 27

cell cycle arrest at G1-S phase

Question 28

What are the clinical uses of calcineurin/mTOR?

Answer 28

transplantation (allograft rejection), autoimmune diseases

Question 29

How do antimetabolites work?

Answer 29

inhibit nucleotide (purine) synthesis

Question 30

What is the exact action of AZA?

Answer 30

- guanine anti-metabolite | - rapidly converted into 6-mercaptopurine

Question 31

What is the exact action of MMF?

Answer 31

- non-competitive inhibitor of IMPDH | - prevents production of guanosine triphosate

Question 32

What effects to antimetabolites have on T and B cells?

Answer 32

- impaired DNA production | - prevents early stages of activated cells proliferation

Question 33

What are the clinical uses of AZA and MMF?

Answer 33

- autoimmune diseases | - allograft rejection

Question 34

What are the clinical uses of MTX?

Answer 34

- RA, PsA, polymyositis, vasculitis | - GvHD in BMT

Question 35

What are the clinical uses of cyclophosphamide?

Answer 35

- vasculitis | - SLE

Question 36

Name 5 biological DMARDs

Answer 36

- anti-cytokines - anti-B cells therapies - anti-T cell activation - anti-adhesion molecules - complement inhibitors

Question 37

What were the first biologics to be used in therapy of RA?

Answer 37

anti-TNF

Question 38

What problems may anti-IL-6 cause?

Answer 38

control of serum lipids

Question 39

What three anti-IL-1 are available?

Answer 39

anakinra, rilonacept and canalinumab

Question 40

What is the action of rituximab?

Answer 40

chimeric mAb against CD20-B cell surface

Question 41

What are the uses of adoptive immunotherapy?

Answer 41

- immunodeficiencies - lymphomas and leukemias - inherited metabolic disorders - autoimmune diseases

Question 42

What are the mechanisms of allergen specific immunotherapy?

Answer 42

- switching of immune response from Th2 (allergic0 to Th1 (allergic) - development of T reg cells and tolerance

Question 43

What are the routes for allergen specific immunotherapy?

Answer 43

SC or sublingual for aero-allergens

Question 44

What are the side-effects of allergen specific immunotherapy?

Answer 44

localised and systemic allergic reactions

Question 45

What are the indications for allergens specific immunotherapy?

Answer 45

- allergic rhinoconjunctivitis not controlled on maximum medical therapy - anaphylaxis to insect venoms

Question 46

Omalizumab acts as a mAb against what?

Answer 46

IgE

Question 47

Mepolizumab acts as a mAb against what?

Answer 47

IL-5

Question 48

What is used in the treatment of asthma?

Answer 48

omalizumab

Question 49

How does mepolizumab work?

Answer 49

prevents eosinophil recruitment and activation