Immunomodulation Flashcards

1
Q

What is immunomodulation?

A

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

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2
Q

What are the various mechanisms that can be used to bring about immunomodulation?

A
  • Immunization
  • Replacement therapy
  • Immune stimulants
  • Immune suppressants
  • Anti-inflammatory agents
  • Allergen immunotherapy (desentization)
  • Adoptive immunotherapy
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3
Q

What are biologic immunomodulators?

A

Medicinal products produced using molecular biology techniques including recombinant DNA technology.

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4
Q

What are the main classes of biologic immunomodulators?

A
  • Substances that are (nearly) identical to the body’s own key signaling proteins
  • Monoclonal antibodies
  • Fusion proteins
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5
Q

What is the problem with biologic immunomodulators?

A

Humans can develop autoantibodies against them.

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6
Q

What is is immunopotentiation?

A

Immunisation

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7
Q

What is the definition of passive immunisation?

A

Transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection

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8
Q

What are the risks associated with passive immunisation?

A
  • Risk of transmission of viruses

- Serum sickness

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9
Q

What types of passive immunisation are available?

A
  • Pooled specific human immunoglobulin

- Animal sera (antitoxins an antivenins)

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10
Q

What are the clinical indications for passive immunisation?

A

Hep B prophylaxis and treatment

Botulism, VZV (pregnancy), diphtheria, snake bites

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11
Q

What is the definition of active immunisation?

A

To stimulate the development of a protective immune response and immunological memory.

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12
Q

What kind of immunogenic material is used in vaccines?

A
  • Weakened forms of pathogens
  • Killed inactivated pathogens
  • Purified materials (proteins, DNA)
  • Adjuvants
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13
Q

What problems are associated with vaccination?

A
  • Allergy to any vaccine component
  • Limited usefulness in immunocompromised
  • Delay in achieving protection
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14
Q

What is pooled human immunoglobulin used for?

A

Rx of antibody deficiency states

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15
Q

What are the various actions of corticosteroids?

A
  • Decreased neutrophil margination
  • Reduced production of inflammatory cytokines
  • Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
  • Lymphopenia
  • Decreased T cells proliferation
  • Reduced immunoglobulins production
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16
Q

What are the side-effects of corticosteroids?

A
  • Carbohydrate and lipid metabolism
    • Diabetes
    • Hyperlipidaemia
  • Reduced protein synthesis
    • Poor wound healing
  • Osteoporosis
  • Glaucoma and cataracts
  • Psychiatric complications
17
Q

What are the uses of corticosteroids?

A
  • Autoimmune diseases
    • CTD, vasculitis, RA
  • Inflammatory diseases
    • Crohn’s, sarcoid, GCA/polymyalgia rheumatica
  • Malignancies
    • Lymphoma
  • Allograft rejection
18
Q

What is calcineurin?

A

Calcineurin (CN) is a calcium and calmodulin dependent serine/threonine protein phosphatase. Activates T cells and stimulates growth and differentiation.

19
Q

Name two calcineurin inhibitors.

A
  • Ciclosporin A (CyA)

- Tacrolimus (FK506)

20
Q

How does ciclosporin work?

A
  • Binds to intracellular protein cyclophilin
  • Prevents activation of NFAT
    Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription
  • Reversible inhibition of T-cell activation, proliferation and clonal expansion
21
Q

How does sirolimus work?

A
  • Also binds to FKBP12 but different effects
  • Inhibits mammalian target of rapamycin (mTOR)
  • Inhibits response to IL-2
  • Cell cycle arrest at G1-S phase
22
Q

How does Azathioprine (AZA) work?

A
  • Guanine anti-metabolite (i.e. purine analogue)
  • Rapidly converted into 6-mercaptopurine
  • Impaired T cell DNA production
23
Q

How does Mycophenolate mofetil work?

A
  • Non-competitive inhibitor of IMPDH
  • Prevents production of guanosine triphosphate
  • Interferes with proliferation of T and B cells
24
Q

What are the clinical uses of cytotoxic drugs?

A
  • AZA/MMF
    • Autoimmune diseases (SLE, vasulitis, IBD)
    • Allograft rejection
  • MTX
    • RA, PsA, Polymyositis, vasculitis
    • GvHD in BMT
  • Cyclophosphamide
    • Vasculitis (Wagner’s, CSS)
    • SLE
25
Q

What are the features of anti-TNF drugs?

A
  • First biologics to be successfully used in therapy of RA (5 different agents now licensed)
  • Used in a number of other inflammatory conditions (Crohn’s, psoriasis, ankylosing spondylitis)
  • Caution: increase risk of TB
26
Q

What are the features of IL-6 drugs?

A
  • Blocks IL-6 receptor
  • Used in therapy of RA and AOSD
  • May cause problems with control of serum lipids
27
Q

What is rituximab?

A
  • Chimeric mAb against CD20- B cell surface
  • Can get rid of B cell producing autoreactive antibodies
  • Used in:
    • Lymphomas, leukaemias
    • Transplant rejection
    • Autoimmune disorders
28
Q

What are the indications for allergen-specific immunotherapy?

A
  • Allergic rhinoconjutivitis not controlled on maximum medical therapy
  • Anaphylaxis to insect venoms
29
Q

What are the mechanisms behind allergen-specific immunotherapy?

A
  • Switching of immune response from Th2 (allergic) to Th1 (non-allergic)
  • Development of T reg cells and tolerance