Organ Transplantation

Disease / Phenomenon

Organ transplantation replaces a failing kidney, liver, heart, lung, pancreas, or intestine with a functioning graft from a living or deceased donor. It is often the only definitive treatment for end-stage organ failure, and outcomes have improved dramatically, yet the central biological obstacle remains: the recipient's immune system recognizes donor tissue as foreign and mounts a response against it. Managing that response requires lifelong immunosuppression, which in turn raises risks of infection, malignancy, nephrotoxicity, and metabolic complications — a permanent balancing act between rejection and over-suppression. Additional challenges include ischemia-reperfusion injury during retrieval and implantation, chronic graft dysfunction, and a persistent shortage of suitable donor organs.

Rejection biology begins with recognition of donor major histocompatibility complex molecules, either directly by recipient T cells or indirectly after processing by recipient antigen-presenting cells. T cell activation requires signal one through the T cell receptor, signal two via CD28-B7 costimulation, and signal three through IL-2 and downstream JAK-STAT and mTOR signaling — the targets of most immunosuppressive agents. Antibody-mediated rejection involves donor-specific antibodies, complement activation, and endothelial injury. Innate inflammation from ischemia-reperfusion, oxidative stress, and TGF-beta-driven fibrosis shape long-term outcomes. This page maps these processes to pathways and biomarkers.