U01.02.035 Transplant rejection

Transplant rejection occurs when the recipient’s immune system identifies the donor tissue as foreign and mounts an immune response against it. The rejection process can vary depending on the time of onset and underlying immunological mechanisms.

Types of Transplant Rejection

Type of Rejection	Onset	Pathogenesis	Features	Management
Hyperacute	Minutes	Pre-existing recipient antibodies react to donor antigens (type II hypersensitivity).	Widespread thrombosis of graft vessels, ischemia/necrosis.	Graft must be removed.
Acute	Weeks to months	Cellular: CD8+ T cells and/or CD4+ T cells react to donor MHCs (type IV hypersensitivity). Humoral: antibodies develop post-transplant.	Vasculitis of graft vessels, dense interstitial lymphocytic infiltrate.	Managed with immunosuppressants.
Chronic	Months to years	CD4+ T cells respond to recipient APCs presenting donor peptides (including allogeneic MHC).	Arteriosclerosis, parenchymal atrophy, interstitial fibrosis, organ-specific features (e.g., chronic allograft nephropathy, bronchiolitis obliterans).	Difficult to reverse; may require a new transplant.
Graft-versus-host disease (GVHD)	Varies	Grafted immunocompetent T cells proliferate and attack host cells (type IV hypersensitivity).	Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly.	Prevent with irradiation of blood products in immunocompromised patients.

Key Points to Remember

Hyperacute Rejection: Occurs rapidly due to pre-existing antibodies and is a type II hypersensitivity response. It leads to thrombosis in graft vessels, resulting in ischemia and necrosis.
Acute Rejection: Can be cellular (via T cells) or humoral (via post-transplant antibodies). It typically involves vasculitis and lymphocytic infiltration of the graft. Immunosuppressants can help manage this form.
Chronic Rejection: Characterized by both cellular and humoral immune responses. It results in long-term graft dysfunction due to arteriosclerosis and fibrosis. Chronic rejection can manifest in specific organ failures like kidney or liver failure.
Graft-versus-Host Disease (GVHD): Seen mainly in bone marrow and liver transplants, where grafted T cells attack the host’s cells. It can be beneficial in certain settings, such as in leukemia treatment, but requires careful management of blood products to prevent infection in immunocompromised patients.

Clinical Examples of Chronic Rejection

Chronic allograft nephropathy: Progressive kidney dysfunction.
Bronchiolitis obliterans: Lung transplant rejection.
Accelerated atherosclerosis: Common in heart transplants.
Vanishing bile duct syndrome: A feature of chronic rejection in liver transplants.

USMLE Step 1 Review Series

Curriculum

U01.02.035 Transplant rejection

Types of Transplant Rejection

Key Points to Remember

Clinical Examples of Chronic Rejection

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