SU13.1-2 | Transplant Immunology and Immunosuppression — Summary & Reflection

KEY TAKEAWAYS

Transplantation replaces failed organs, but its central obstacle is immunological rejection of the allograft. The graft is recognised as foreign chiefly through the HLA/MHC system: class I (HLA-A, B, C) on all nucleated cells presenting to CD8 T cells, and class II (HLA-DR, DQ, DP) on antigen-presenting cells presenting to CD4 T cells, with HLA-A, -B and -DR mattering most for matching. ABO compatibility and a negative crossmatch are mandatory; a positive crossmatch predicts hyperacute rejection. Rejection comes in three patterns by timing and mechanism: hyperacute (minutes-hours, preformed antibodies, untreatable, prevented by matching), acute (days-weeks, predominantly cell-mediated, reversible with intensified immunosuppression) and chronic (months-years, fibrosis and vasculopathy, treatment-resistant, the main cause of late graft loss); graft-versus-host disease is the reverse attack by donor cells. Immunosuppression is given as induction (e.g. basiliximab, anti-thymocyte globulin) then lifelong maintenance combining calcineurin inhibitors (ciclosporin, tacrolimus — nephrotoxic), antiproliferatives (mycophenolate, azathioprine — marrow suppression), corticosteroids and mTOR inhibitors (sirolimus, everolimus). The unavoidable price is increased infection and malignancy risk — the balance every transplant recipient lives with.

REFLECT

Think about a patient you have seen with end-stage organ failure — someone on dialysis, or awaiting a liver or heart. If a graft became available, what immunological steps would have to be cleared before the operation, and what would you be watching for in the first days, the first months and the first years afterwards? Consider, too, the trade-off at the heart of immunosuppression: every increase in dose buys protection against rejection but pays for it in infection and cancer risk. How would understanding this balance change the way you counsel a transplant candidate about what life with a new organ — and its medicines — actually involves?