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Intensive care unit nurses and advanced practice registered nurses need a working knowledge of transplant immunology because daily decisions about rejection surveillance, immunosuppressive medication management, early recognition of rejection risk, and patient education are grounded in these mechanisms. Recipient alloactivation occurs through direct and indirect pathways that shape the timing and phenotype of rejection. Acute cellular rejection is primarily T-cell mediated through major histocompatibility complex interactions, while antibody-mediated rejection is driven by donor-specific antibodies against human leukocyte antigens with complement activation and endothelial injury. 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