Immuno: Immune modulating therapies Pt.4 Flashcards
List some indications for plasmapheresis.
Severe antibody-mediated disease
- Goodpasture’s disease
- Severe acute myasthenia gravis
- Antibody-mediated tranplant rejection
Describe the mechanism of action of calcineurin inhibitors.
- 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
Give two examples of calcineurin inhibitors.
- Ciclosporin
- Tacrolimus
List some indications for calcineuin inhibitors
- Transplantation
- Rheumatoid arthritis
- Severe atopic eczema
- Psoriasis and psoriatic arthritis
- IBD (UC)
What are the adverse-effects of calcineurin inhibitors?
- Increased risk of infection
- Hypertension
- Nephrotoxicty
- (also diabetes, neurotoxic and dysmporphic facies)
What is the function of mTOR inhibitors and give an example?
Sirolimus - inhibits T cell activation and proliferation
Give an example of a JAK inhibitor.
Describe the mechanism of action of JAK inhibitors.
Tofacitinib (JAK1 and JAK3 inhibitor)
- Inhibits JAK-STAT signalling (associated with cytokine receptors)
- Influences gene expression thus inhibiting the production of inflammatory molecules
What are some indications for JAK inhibitors?
- Rheumatoid arthritis
- Ulcerative colitis
- Psoriatic arthritis
- Axial spondyloarthritis
Give an example of a PDE4 inhibitor.
Apremilast
What are some indications for PDE4 inhibitors?
- Psoriasis
- Psoriatic arthritis
For each of the following monoclonal antibodies, their basic mechanism of action
- Basiliximab
- Abatacept
- Rituximab
- Vedolizumab
- Natalizumab
- Basiliximab = anti-CD25 (alpha chain of IL-2 receptor)
- Abatacept = CLTA4-Ig
- Rituximab = anti-CD20
- Vedolizumab = anti-alpha4beta7 integrin
- Natalizumab = anti-alpha4beta1 integrin
What does the suffix (-cept) mean?
It is made up of a receptor fused to immunoglobulin
Describe how anti-thymocyte globulin is made. What is it used for?
- 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
List some adverse-effects of anti-thymocyte globulin.
- Infusion reactions
- Leukopaenia
- Infection
- Malignancy
Describe the mechanism of action of basiliximab/daclizumab. What is the indication for its use?
- 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
What are some adverse effects of basilximab/daclizumab?
- Infusion reaction
- Infection
- Increases long term malignancy risk
Describe the mechanism of action of abatacept. What condition is it used for?
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
Describe the mechanism of action of rituximab.
- Targets CD20 which is found on mature B cells
- This results in depletion of mature B cells
- No effect on plasma cells
List some indications for rituximab.
- B cell Lymphoma
- Rheumatoid arthritis
- SLE
NOTE: it is given as two IV doses every 6-12 months
What are some adverse-effects of rituximab?
- Infusion reaction
- Infection (PML)
- Exacerbation of CVD
