1. Why are immunosuppressant drugs needed?
    • 1. Suppress hosts response to organ transplant (host vs graft)
    • 2. Suppress lymphocytes in graft's response to host (bone marrow vs host)
    • 3. Treat autoimmune conditions (ulcerative colitis)
  2. Characterise the 4 different type of immunosuppressants and give examples.
    • 1. Inhibition of IL-2 production/action- Ciclosporin
    • 2. Inhibition of cytokine gene expression- Corticosteroids
    • 3. Inhibition of purine/pyrimidine synthesis- Cytotoxic agents
    • 4. Blockage of T-cell surface molecules- Monoclonal antibodies against IL-2 receptor
  3. What is ciclosporin and what is it used to treat?
    • Cyclic peptide of 11 amino acids
    • Found in fungus
    • Potent immunosuppressant
    • Drug of choice in organ transplantation
    • Also used to treat autoimmune diseases
  4. What is the normal series of events that occurs to cause IL-2 gene transcription?
    • Antigen binds to Th cell
    • Intracellular Ca2+ increases
    • Phosphatase activated
    • Dephosphorylates to activate transcription factors
    • IL-2 transcribed
  5. What is the role of IL-2 in the immune response?
    IL-2 is necessary for the development of T cell immunological memory, which depends upon the expansion of the number and function of antigen-selected T cell clones.
  6. What is the mechanism of action of ciclosporin?
    • Ciclosporin binds to cyclophillin
    • This complex binds to and inhibits the phosphatase
    • IL-2 transcription is not initiated
    • Th cells are not activated
  7. What is the result of the use of ciclosporin?
    • T-cell proliferation is inhibited
    • The induction and effector phase of the immune response is inhibited
  8. What are the side effects of ciclosporin?
    • Nephrotoxicity
    • Hepatotoxicity
  9. Give a summary and example of glucocorticoids.
    • Used in organ transplants and to treat autoimmune diseases.
    • Prevents clonal proliferation of Th cells by downregulation of IL-2 transcription and other cytokines involved in the induction and effector phase of the immune response.
    • Inflammatory actions also.
    • Eg Hydrocortisone and Dexamethosone
  10. What is the mechanism of action of the glucocorticoids?
    • Steroid binds to intracellular receptor.
    • Steroid-receptor complex acts as a transcription factor
    • Induces transcription of genes, some of which inhibit IL-2 and other cytokine transcription
  11. What are the side effects of glucocorticoids?
    • Suppress response to infection
    • Osteoporosis
    • Muscle wasting
    • Hyperglycaemia
  12. What is the general action of cytotoxic agents?
    • Cytotoxic agents inhibit the proliferation of cells within the body.
    • They inhibit the proliferation of T and B cells in a specific immune response.
    • They affect DNA synthesis to inhibit cell division and proliferation.
    • Adverse effects include bone marrow depression.
  13. What is the mechanism of the cytotoxic drug azathioprine?
    It is metabolised in the body to form a purine analogue,mercaptopurine, which causes inhibition of DNA synthesis.
  14. What is the mechanism of the cytotoxic drug cyclophosamide?
    • It cross links DNA strands to inhibit DNA synthesis.
    • This causes inhibition of T and B cell proliferation.
  15. Give a summary of monoclonal antibodies against IL-2 receptors?
    • Eg Basiliximab
    • Blocks the IL-2 receptor
    • Inhibits clonal expansion of T-cells in the specific immune response
    • Side effect- hypersensitivity
  16. Give an example of an inherited and aquired immunodeficiency disease?
    • Inherited:
    • Leukocyte adhesion defieciency
    • -defective leukocyte recruitment to infected tissue.

    • Aquired:
    • AIDS
    • -deletion of CD4 T-cells by HIV virus
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