Acute rejection after transplantation is primarily mediated by which immune process and when does it occur?

• A. Hyperacute rejection is mediated by preformed antibodies
• B. Graft-versus-host disease: donor T cells attack host
• C. Chronic rejection: fibrosis months later
• D. Acute rejection: CD8+ T cells reacting against foreign MHCs - occurs weeks after transplant

Answer: (D)

Acute rejection is driven by a T-cell–mediated immune response against the donor graft. Recipient CD8+ cytotoxic T cells recognize donor MHC class I antigens presented on graft cells (direct allorecognition) and become activated, proliferate, and kill graft cells via perforin/granzyme pathways and inflammatory cytokines. This cellular attack typically becomes evident weeks after transplantation as the adaptive immune response develops against the foreign MHCs. By contrast, hyperacute rejection occurs within minutes to hours because of preformed recipient antibodies against donor antigens; chronic rejection arises months to years later with fibrosis and vascular changes; and graft-versus-host disease involves donor T cells attacking the host, usually after bone marrow transplantation.