Immunosuppression

• 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)

• 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

• Cyclic peptide of 11 amino acids
• Found in fungus
• Potent immunosuppressant
• Drug of choice in organ transplantation
• Also used to treat autoimmune diseases

• Antigen binds to Th cell
• Intracellular Ca2+ increases
• Phosphatase activated
• Dephosphorylates to activate transcription factors
• IL-2 transcribed

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.

• Ciclosporin binds to cyclophillin
• This complex binds to and inhibits the phosphatase
• IL-2 transcription is not initiated
• Th cells are not activated

• T-cell proliferation is inhibited
• The induction and effector phase of the immune response is inhibited

• Nephrotoxicity
• Hepatotoxicity

• 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

• 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

• Suppress response to infection
• Osteoporosis
• Muscle wasting
• Hyperglycaemia

• 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.

It is metabolised in the body to form a purine analogue,mercaptopurine, which causes inhibition of DNA synthesis.

• It cross links DNA strands to inhibit DNA synthesis.
• This causes inhibition of T and B cell proliferation.

• Eg Basiliximab
• Blocks the IL-2 receptor
• Inhibits clonal expansion of T-cells in the specific immune response
• Side effect- hypersensitivity

• Inherited:
• Leukocyte adhesion defieciency
• -defective leukocyte recruitment to infected tissue.

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