|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.
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).|