Hyperacute graft rejection is best explained by which immunologic mechanism?

• A. Type I hypersensitivity with IgE-mediated mast cell degranulation
• B. Type IV hypersensitivity T cell-mediated
• C. Type III immune complex deposition
• D. Type II hypersensitivity with antibody-mediated vascular injury and complement activation

Answer: (D)

Hyperacute graft rejection is driven by preformed antibodies against donor antigens, such as ABO or HLA, that bind to the donor endothelium and fix complement. This antibody binding sets off a cascade that injures the vascular lining, activates platelets, and causes rapid thrombosis of graft vessels, leading to immediate graft failure. This is the classic Type II hypersensitivity mechanism: antibody-mediated destruction of target cells or tissues with complement involvement.

In contrast, a Type I response involves IgE and mast cell degranulation (allergic reactions), a Type IV response is a delayed T cell–mediated reaction, and a Type III response involves immune complex deposition. The rapid vascular injury and clotting seen in hyperacute rejection point to the antibody-mediated, complement-activating process described here.