Correct Answer: D. Type II
Hyperacute rejection occurs within minutes to hours of transplantation and is mediated by Type II hypersensitivity (cytotoxic antibody-mediated) reactions. The mechanism involves pre-existing IgG and IgM antibodies against donor HLA antigens (or ABO blood group antigens) in the recipient's circulation. These antibodies bind to the vascular endothelium of the transplanted organ, activating the classical complement pathway, leading to complement-mediated endothelial cell lysis, thrombosis, and immediate graft necrosis. This is why ABO blood group compatibility and HLA cross-matching are mandatory before renal transplantation in Indian transplant centers. The histology shows fibrinoid necrosis of vessel walls and platelet aggregation. Unlike delayed rejection (Type IV), hyperacute rejection cannot be reversed by immunosuppression because the damage is already done within the first few hours. This is a Type II hypersensitivity because it involves antibody binding to cell-surface antigens followed by complement activation and cell destruction—the hallmark of cytotoxic antibody reactions.
Why the other options are wrong
A. Type III — Type III hypersensitivity (immune complex-mediated) is responsible for chronic rejection, not hyperacute rejection. It occurs weeks to months post-transplant and involves circulating antigen-antibody complexes depositing in vessel walls. Hyperacute rejection is too rapid (minutes to hours) for immune complex formation and deposition to be the primary mechanism. B. Type I — Type I hypersensitivity (IgE-mediated, immediate allergic) involves mast cell and basophil degranulation and is responsible for anaphylaxis and allergic reactions. It has no role in transplant rejection. The antibodies in hyperacute rejection are IgG and IgM (complement-fixing), not IgE. C. Type IV — Type IV hypersensitivity (cell-mediated, delayed) is responsible for acute and chronic rejection occurring days to weeks post-transplant, mediated by T cells and macrophages. Hyperacute rejection occurs too rapidly (within hours) for T-cell priming and infiltration; it is antibody-mediated, not cell-mediated.
High-Yield Facts
- Hyperacute rejection occurs within minutes to hours; mediated by pre-existing IgG/IgM antibodies against donor HLA or ABO antigens.
- Type II hypersensitivity mechanism: antibody binding to cell surface → complement activation → cytotoxic cell lysis and thrombosis.
- ABO blood group matching and HLA cross-matching are mandatory pre-transplant screening in Indian renal transplant protocols to prevent hyperacute rejection.
- Histology of hyperacute rejection: fibrinoid necrosis of vessel walls, platelet aggregation, and neutrophilic infiltration within hours.
- Hyperacute rejection is irreversible because graft destruction occurs before immunosuppression can take effect; prevention is the only strategy.
Mnemonics
REJECTION TIMELINE & MECHANISM Hyperacute (minutes–hours) = Type II (antibody); Acute (days–weeks) = Type IV (T-cell); Chronic (months–years) = Type III (immune complex). Use: Remember that the faster the rejection, the earlier the immune mechanism (antibody before T-cell). TYPE II HYPERSENSITIVITY = CYTOTOXIC Cell-surface antigen + Compliment = Cell death. Antibody binds → complement cascade → lysis. Use: Whenever you see 'antibody + complement + cell death,' think Type II.
NBE Trap
NBE may pair "transplant rejection" with Type IV (cell-mediated) because acute rejection is indeed Type IV; students who conflate hyperacute with acute rejection will choose Type IV. The discriminator is timing: hyperacute = minutes to hours (antibody-mediated), acute = days to weeks (T-cell mediated).
Clinical Pearl
In Indian transplant centers, a positive HLA cross-match (indicating pre-existing donor-specific antibodies) is an absolute contraindication to transplantation because it guarantees hyperacute rejection within hours. This is why sensitized recipients (those with multiple transfusions or prior transplants) require desensitization protocols before renal transplantation.
_Reference: Robbins & Cotran Pathologic Basis of Disease, Ch. 6 (Diseases of Immunity); Harrison's Principles of Internal Medicine, Ch. 124 (Transplantation); Jawetz, Melnick & Adelberg's Medical Microbiology, Ch. 58 (Immunology of Transplantation)_