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YEAR 5: Immunopathology > Immuno: Immune modulating therapies Pt.4 > Flashcards

Immuno: Immune modulating therapies Pt.4 Flashcards

1
Q

List some indications for plasmapheresis.

A

Severe antibody-mediated disease

  • Goodpasture’s disease
  • Severe acute myasthenia gravis
  • Antibody-mediated tranplant rejection
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2
Q

Describe the mechanism of action of calcineurin inhibitors.

A
  • Normally, TCR engagement leads to increased cytoplasmic calcium which binds to calmodulin leading to the activation of calcineurin
  • Calcineurin then activates NFATc resulting in the upregulation of IL-2
  • IL-2 acts back on T cells to stimulate activation and proliferation

Calcineurin inhibitors block this pathway, thereby blocking IL -2 production

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3
Q

Give two examples of calcineurin inhibitors.

A
  • Ciclosporin
  • Tacrolimus
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4
Q

List some indications for calcineuin inhibitors

A
  • Transplantation
  • Rheumatoid arthritis
  • Severe atopic eczema
  • Psoriasis and psoriatic arthritis
  • IBD (UC)
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5
Q

What are the adverse-effects of calcineurin inhibitors?

A
  • Increased risk of infection
  • Hypertension
  • Nephrotoxicty
  • (also diabetes, neurotoxic and dysmporphic facies)
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6
Q

What is the function of mTOR inhibitors and give an example?

A

Sirolimus - inhibits T cell activation and proliferation

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7
Q

Give an example of a JAK inhibitor.
Describe the mechanism of action of JAK inhibitors.

A

Tofacitinib (JAK1 and JAK3 inhibitor)

  • Inhibits JAK-STAT signalling (associated with cytokine receptors)
  • Influences gene expression thus inhibiting the production of inflammatory molecules
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8
Q

What are some indications for JAK inhibitors?

A
  • Rheumatoid arthritis
  • Ulcerative colitis
  • Psoriatic arthritis
  • Axial spondyloarthritis
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9
Q

Give an example of a PDE4 inhibitor.

A

Apremilast

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10
Q

What are some indications for PDE4 inhibitors?

A
  • Psoriasis
  • Psoriatic arthritis
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11
Q

For each of the following monoclonal antibodies, their basic mechanism of action

  1. Basiliximab
  2. Abatacept
  3. Rituximab
  4. Vedolizumab
  5. Natalizumab
A
  1. Basiliximab = anti-CD25 (alpha chain of IL-2 receptor)
  2. Abatacept = CLTA4-Ig
  3. Rituximab = anti-CD20
  4. Vedolizumab = anti-alpha4beta7 integrin
  5. Natalizumab = anti-alpha4beta1 integrin
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12
Q

What does the suffix (-cept) mean?

A

It is made up of a receptor fused to immunoglobulin

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13
Q

Describe how anti-thymocyte globulin is made. What is it used for?

A
  • Human thymocytes (T cells and their precursors) are injected into a rabbit which produces a variety of antibodies against thymocytes
  • This is then injected into patients and leads to T cell depletion
  • It is effective in allograft transplant rejection
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14
Q

List some adverse-effects of anti-thymocyte globulin.

A
  • Infusion reactions
  • Leukopaenia
  • Infection
  • Malignancy
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15
Q

Describe the mechanism of action of basiliximab/daclizumab. What is the indication for its use?

A
  • Targets CD25 (alpha chain of IL-2 receptor)
  • Blocks IL-2R thus inhibiting T cell activation and proliferation
  • Used as a prophylaxis against transplant rejection
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16
Q

What are some adverse effects of basilximab/daclizumab?

A
  • Infusion reaction
  • Infection
  • Increases long term malignancy risk
17
Q

Describe the mechanism of action of abatacept. What condition is it used for?

A

Used in rheumatoid arthritis

  • APCs bind to T cell CTLA4 (inhibitory) and CD28 (stimulatory) via CD80 and CD86 receptors
  • Abatacept binds to CD80 and CD86 and prevents CD28 engagement thus inhibiting co-stimulation required for T cell activation
18
Q

Describe the mechanism of action of rituximab.

A
  • Targets CD20 which is found on mature B cells
  • This results in depletion of mature B cells
  • No effect on plasma cells
19
Q

List some indications for rituximab.

A
  • B cell Lymphoma
  • Rheumatoid arthritis
  • SLE

NOTE: it is given as two IV doses every 6-12 months

20
Q

What are some adverse-effects of rituximab?

A
  • Infusion reaction
  • Infection (PML)
  • Exacerbation of CVD

YEAR 5: Immunopathology (25 decks)

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