Theme 2 Lecture 10: Immunomodulation and Immunosuppression

Question 1

What is immunomodulation?

Answer 1

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

Question 2

What are immunomodulators?

Answer 2

medicinal products produced using molecular biology techniques including recombinant DNA technology

Question 3

What are the 3 main classes of immunomodulators?

Answer 3

• substances that are (nearly) identical to the body’s own key signalling proteins
• monoclonal antibodies
• fusion proteins

Question 4

What are 4 examples of immunomodulators?

Answer 4

• adalimumab
• infliximab
• etabercept
• cetrolizumab

Question 5

Which cytokine to immunomodulators target?

Answer 5

TNF

Question 6

What is immunopotentiation?

Answer 6

enhancement of the immune response by increasing the speed and extent of its development and by prolonging its duration

Question 7

What is passive immunisation?

Answer 7

• the transfer of specific, high-titre antibody from donor to recipient
• provides immediate but transient protection

Question 8

What are the problems of immunisation?

Answer 8

• risk of transmission of viruses

- serum sickness (type 3 hypersensitivity)

Question 9

In what situations do we use immunisation?

Answer 9

• COVID-19
• HepB prophylaxis and treatment
• botulism
• diptheria
• snake bites

Question 10

What is active immunisation?

Answer 10

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

Question 11

What are the 4 types of immunogenic material?

Answer 11

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

Question 12

What are adjuvants?

Answer 12

chemicals that can stimulate a particular type of immune response

Question 13

What are the problems with active immunisation?

Answer 13

• allergy to any vaccine component
• limited usefulness in immunocompromised
• delay in achieving protection

Question 14

What are 3 examples of replacement therapies and immune stimulation?

Answer 14

• pooled human immunoglobulin
• G-CSF/ GM-CSF - act on bone marrow to increase production of mature neutrophils
• Y-interferon - used in CGD

Question 15

Explain the action of corticosteroids

Answer 15

• immunosuppressive agent
• decreased neutrophil margination
• reduced production of inflammatory cytokines
• inhibition phospholipase A2
• lymphopenia
• decreased T cell proliferation
• reduced immunoglobulins production

Question 16

What are the side effects of corticosteroids?

Answer 16

• carbohydrate and lipid metabolism - diabetes and hyperlipidaemia
• reduced protein synthesis - poor wound healing
• osteoporosis
• glaucoma and cataracts
• psychiatric complications

Question 17

What are all the uses of corticosteroids?

Answer 17

• autoimmune diseases - CGD, RA, vasculitis
• inflammatory diseases - chron’s, sarcoid
• malignancies - lymphoma
• allograft rejection (prevention)

Question 18

What are the 4 main categories of drugs that target lymphocytes and give an example of each?

Answer 18

1. antimetabolites
   - azathioprine (AZA)
   - prevent T cell proliferation
2. calcineurin inhibitors
   - ciclosporin A
3. M-TOR inhibitors
   - sirolimus inhibits T cell activation
4. IL-2 receptor mABs
   - basiliximab

Question 19

How do calcineurin inhibitors work?

Answer 19

• CyA - bind to intracellular protein cyclophillin
• prevents activation of NFAT and therefore T cell stimulation
• reversible inhibition of T cell activation, proliferation and clonal expansion

Question 20

What are the potential side effects of calcineurin?

Answer 20

• hypertension
• hirsutism
• nephrotoxicity
• hepatotoxicity
• lymphomas
• opportunistic infections
• neurotoxicity

Question 21

What is the mode of action of sirolimus?

Answer 21

• inhibits response of IL-2

- cell cycle arrest at G1-S phase

Question 22

What is the clinical use of calcineurin?

Answer 22

• transplantation - allograft rejection

- autoimmune disease

Question 23

How do antimetabolites work?

Answer 23

• inhibit nucleotide (purine) synthesis
• azathioprine is a guanine anti-metabolite
• T and B cell effects - impaired NDA production, prevents early stages of activated cells proliferation

Question 24

What is methotrexate?

Answer 24

folate antagonist

Question 25

What are the side effects of cytotoxic drugs in general?

Answer 25

• target all dividing cells
• bone marrow suppression
• gastric upset
• hepatits
• susceptibility to infections
• cystitis (cylophosphamide)
• pneumonitis (methotrexate)

Question 26

What is an allograft?

Answer 26

transplant of an organ from one individual to another of the same species with a different genotype

Question 27

What is cyclophosphamide used to treat?

Answer 27

• vasculitis (Wagner’s, CSS)

- SLE

Question 28

What do anti adhesion molecules do?

Answer 28

prevent migration of immune cells to sites of disease

Question 29

What is Anti IL-6 and what is it used for?

Answer 29

• blocks IL-6 receptor

- used in therapy of RA and AOSD (rare form of arthiritis)

Question 30

What is the risk of anti-TNF?

Answer 30

Increased risk of Tb

Question 31

What is rituximab?

Answer 31

-chimeric (part mouse part human) mAb against CD20-B cell surface

Question 32

What are the uses of rituximab?

Answer 32

• lymphomas, leukaemias
• transplant rejection
• autoimmune disorders

Question 33

What is adoptive immunotherapy and when is it used?

Answer 33

• bone marrow transplant
• stem cell transplant
• essentially replace the immune system with a functioning one
• uses: immunodeficiencies (SCID), lymphomas and leukaemias, autoimmune diseases

Question 34

Which classes of drugs can be used for treatment of allergies?

Answer 34

• immune suppressants
• allergen specific immunotherapy
• anti-IgE monoclonal therapy
• anti-IL-5 monoclonal treatment

Question 35

What is omalizumab?

Answer 35

• mAB against IgE
• used in asthma
• chronic urticaria and angioedema
• may cause severe systemic anaphylaxis