Immune‑mediated injury to a transplanted tissue or organ caused by recipient recognition of donor antigens, manifesting as loss or deterioration of graft‑specific function and corroborated by histologic, immunopathologic, or serologic evidence of immune attack.

Principle

When recipient adaptive immune responses target non‑self donor antigens (cellular or humoral), they produce inflammatory and cytotoxic processes that damage graft parenchyma and vasculature; the dominant effector mechanism and timing (e.g., acute cellular, antibody‑mediated, chronic) shape clinical presentation and potential reversibility.

Demonstration

Illustrative scenario — Situation: a recent renal transplant patient develops progressive graft dysfunction. Recognition: diagnostic evaluation shows declining function plus biopsy evidence of immune infiltrate or antibody deposition. Action: clinicians adjust immunomodulatory therapy targeted to the identified mechanism. Consequence: early, mechanism‑directed therapy can halt or reverse injury; delayed or absent recognition permits ongoing immune damage and possible graft loss.

Misapplication

Attributing any post‑transplant graft dysfunction to 'rejection' without excluding non‑immune causes (ischemia, thrombosis, technical failure, infection or drug toxicity). The error is conflating outcome (dysfunction) with mechanism (immune injury).

Consequence

Correctly identifying rejection directs immunologic interventions and monitoring strategies; failure to detect the immune mechanism permits continued immune‑mediated injury, increasing risk of irreversible structural damage and graft failure.

Reversal

Exceptions occur when alloantigen is present without immune injury (e.g., established immune tolerance, mixed chimerism, or effective desensitization), or when immune markers are present without tissue damage; therefore diagnosis requires correlation between immune evidence and objective graft injury.

Boundary

Clearly within: biopsy‑proven cellular or antibody‑mediated lesion with concurrent loss of graft function. Boundary case: isolated subclinical histologic immune activity without measurable functional decline. Clearly outside: graft dysfunction due solely to surgical thrombosis, ischemic necrosis, or infection without immunopathologic evidence.

Semantic Tension

Preventing immune injury by intensifying immunosuppression ↔ increasing the patient's risk of infection, malignancy and drug toxicity; diagnostic certainty ↔ urgency of treatment.

Synthesis

Rejection is a mechanistic diagnosis—an immune process distinct from the endpoint 'graft failure'—so management depends on correctly attributing dysfunction to immune mechanisms rather than treating the outcome alone.