Transplant Rejection

TYPE OF REJECTION ONSET PATHOGENESIS FEATURES MORPHOLOGY
Hyperacute Within minutes Pre-existing recipient antibodies react to donor antigen (type II hypersensitivity reaction), activate complement. Widespread arterial fibrinoid necrosis, thrombosis of graft vessels → ischemia/necrosis. Graft must be removed. Gross mottling and cyanosis. Arterial fibrinoid necrosis & capillary thrombotic occlusion.
A  cute Weeks to months Cellular: CD8+ T cells and/or CD4+ T cells activated against donor MHCs (type IV hypersensitivity reaction. Humoral: similar to hyperacute, with C4d deposition, neutrophilic infiltrate except antibodies develop after transplant. Vasculitis (humoral) of graft vessels with dense interstitial lymphocytic (cellular) infiltrate. Prevent/reverse with immunosuppressants (cyclosporine, tacrolimus + glucocorticoids) Humoral: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis

Cellular: Lymphocytic interstitial infiltrate and endothelitis

Chronic Months to years CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC.

Both cellular and humoral components (type II and IV hypersensitivity reactions).

Recipient T cells react and secrete cytokines → proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fibrosis. Dominated by arteriosclerosis.

Organ-specific examples:

Bronchiolitis obliterans (lung)

Accelerated atherosclerosis (heart)

Chronic graft nephropathy (kidney)

Vanishing bile duct syndrome (liver)

Vascular wall thickening & luminal narrowing

Interstitial fibrosis & parenchymal atrophy

Graft-versus-host disease Varies Grafted immunocompetent CD4+ and CD8+ T cells proliferate in the immunocompromised host and reject host cells with “foreign” proteins → severe organ dysfunction. Type IV hypersensitivity reaction. Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usually in bone marrow and liver transplants (rich in lymphocytes). Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect).  

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