Hyperacute rejection of a transplanted organ is mediated primarily by which immune mechanism?

• A. Preformed host antibodies against donor HLA or ABO antigens causing complement-mediated injury.
• B. T cell-mediated cytotoxicity against donor antigens.
• C. Immune complex deposition in graft vessels.
• D. Delayed-type hypersensitivity against donor peptides.

Answer: (A)

Hyperacute rejection occurs when preformed antibodies in the recipient recognize donor antigens (most notably ABO antigens or HLA antigens) on the transplanted tissue. These antibodies bind to the donor endothelium and activate the classical complement pathway, leading to rapid injury of the graft vessels, widespread thrombosis, ischemia, and very rapid graft failure—often within minutes to hours. This is why the correct description emphasizes preformed host antibodies against donor HLA or ABO antigens causing complement-mediated injury.

T cell–mediated cytotoxicity is typical of acute cellular rejection that arises days to weeks after transplant. Immune complex deposition describes a different pattern of immune injury, and delayed-type hypersensitivity against donor peptides also points to a T-cell–driven process that occurs later. The hyperacute scenario is specifically antibody- and complement–driven, reflecting preexisting antibodies that target the graft before it has a chance to function.