Theme 2 Lecture 10: Immunomodulation and Immunosuppression Flashcards Preview

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Flashcards in Theme 2 Lecture 10: Immunomodulation and Immunosuppression Deck (35)
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1
Q

What is immunomodulation?

A

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

2
Q

What are immunomodulators?

A

medicinal products produced using molecular biology techniques including recombinant DNA technology

3
Q

What are the 3 main classes of immunomodulators?

A
  • substances that are (nearly) identical to the body’s own key signalling proteins
  • monoclonal antibodies
  • fusion proteins
4
Q

What are 4 examples of immunomodulators?

A
  • adalimumab
  • infliximab
  • etabercept
  • cetrolizumab
5
Q

Which cytokine to immunomodulators target?

A

TNF

6
Q

What is immunopotentiation?

A

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

7
Q

What is passive immunisation?

A
  • the transfer of specific, high-titre antibody from donor to recipient
  • provides immediate but transient protection
8
Q

What are the problems of immunisation?

A
  • risk of transmission of viruses

- serum sickness (type 3 hypersensitivity)

9
Q

In what situations do we use immunisation?

A
  • COVID-19
  • HepB prophylaxis and treatment
  • botulism
  • diptheria
  • snake bites
10
Q

What is active immunisation?

A

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

11
Q

What are the 4 types of immunogenic material?

A
  • weakened forms of pathogen
  • killed inactivated pathogens
  • purified materials (proteins, DNA, RNA)
  • adjuvants
12
Q

What are adjuvants?

A

chemicals that can stimulate a particular type of immune response

13
Q

What are the problems with active immunisation?

A
  • allergy to any vaccine component
  • limited usefulness in immunocompromised
  • delay in achieving protection
14
Q

What are 3 examples of replacement therapies and immune stimulation?

A
  • pooled human immunoglobulin
  • G-CSF/ GM-CSF - act on bone marrow to increase production of mature neutrophils
  • Y-interferon - used in CGD
15
Q

Explain the action of corticosteroids

A
  • immunosuppressive agent
  • decreased neutrophil margination
  • reduced production of inflammatory cytokines
  • inhibition phospholipase A2
  • lymphopenia
  • decreased T cell proliferation
  • reduced immunoglobulins production
16
Q

What are the side effects of corticosteroids?

A
  • carbohydrate and lipid metabolism - diabetes and hyperlipidaemia
  • reduced protein synthesis - poor wound healing
  • osteoporosis
  • glaucoma and cataracts
  • psychiatric complications
17
Q

What are all the uses of corticosteroids?

A
  • autoimmune diseases - CGD, RA, vasculitis
  • inflammatory diseases - chron’s, sarcoid
  • malignancies - lymphoma
  • allograft rejection (prevention)
18
Q

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

A
  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
19
Q

How do calcineurin inhibitors work?

A
  • 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
20
Q

What are the potential side effects of calcineurin?

A
  • hypertension
  • hirsutism
  • nephrotoxicity
  • hepatotoxicity
  • lymphomas
  • opportunistic infections
  • neurotoxicity
21
Q

What is the mode of action of sirolimus?

A
  • inhibits response of IL-2

- cell cycle arrest at G1-S phase

22
Q

What is the clinical use of calcineurin?

A
  • transplantation - allograft rejection

- autoimmune disease

23
Q

How do antimetabolites work?

A
  • 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
24
Q

What is methotrexate?

A

folate antagonist

25
Q

What are the side effects of cytotoxic drugs in general?

A
  • target all dividing cells
  • bone marrow suppression
  • gastric upset
  • hepatits
  • susceptibility to infections
  • cystitis (cylophosphamide)
  • pneumonitis (methotrexate)
26
Q

What is an allograft?

A

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

27
Q

What is cyclophosphamide used to treat?

A
  • vasculitis (Wagner’s, CSS)

- SLE

28
Q

What do anti adhesion molecules do?

A

prevent migration of immune cells to sites of disease

29
Q

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

A
  • blocks IL-6 receptor

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

30
Q

What is the risk of anti-TNF?

A

Increased risk of Tb

31
Q

What is rituximab?

A

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

32
Q

What are the uses of rituximab?

A
  • lymphomas, leukaemias
  • transplant rejection
  • autoimmune disorders
33
Q

What is adoptive immunotherapy and when is it used?

A
  • bone marrow transplant
  • stem cell transplant
  • essentially replace the immune system with a functioning one
  • uses: immunodeficiencies (SCID), lymphomas and leukaemias, autoimmune diseases
34
Q

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

A
  • immune suppressants
  • allergen specific immunotherapy
  • anti-IgE monoclonal therapy
  • anti-IL-5 monoclonal treatment
35
Q

What is omalizumab?

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

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