Learning Objective

At the end of this topic, the student should be able to differentiate among hyperacute, acute, chronic transplant rejection, and graft-versus-host disease by understanding their onset, pathogenesis, clinical features, and underlying immunologic mechanisms.

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Transplant rejection represents the immune system’s response against a transplanted organ or tissue. The type of rejection depends on the timing, mechanism of immune activation, and histopathological findings.

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Activity

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Hyperacute Rejection

Onset

• Within minutes after transplantation

Pathogenesis

• Pre-existing recipient IgG antibodies react to donor antigens (ABO blood group or HLA)
• Mediates a type II hypersensitivity reaction
• Complement activation causes the rapid destruction of the graft vasculature

Key Features

• Widespread thrombosis of graft vessels
• Ischemia and fibrinoid necrosis
• Graft becomes cyanotic and must be removed immediately
  → This occurs due to previous exposure, such as prior transplant, pregnancy, or blood transfusion

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Acute Rejection

Onset

• Weeks to months after transplant

Pathogenesis

Cellular Pathway

• CD4⁺ and CD8⁺ T-cells recognize donor MHC and attack the graft
  → Type IV hypersensitivity

Humoral Pathway

• New donor-specific antibodies develop after transplant
  → Complement involvement may show C4d deposition

Key Features

• Vasculitis affecting graft vessels
• Dense interstitial lymphocytic infiltrate
• Responds to immunosuppressive therapy (e.g., steroids, calcineurin inhibitors)

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Activity

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Chronic Rejection

Onset

• Months to years after transplantation

Pathogenesis

• Chronic low-grade T-cell response against donor antigens presented on recipient APCs
• Mixed cellular and antibody-mediated injury
  → Type II and IV hypersensitivity mechanisms

Key Features

• Dominated by progressive arteriosclerosis
• Vascular smooth muscle proliferation due to cytokines
• Chronic inflammation → fibrosis and parenchymal atrophy

Organ-specific manifestations

• Chronic allograft nephropathy (kidney)
• Bronchiolitis obliterans (lung)
• Accelerated coronary atherosclerosis (heart)
• Vanishing bile duct syndrome (liver)

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Graft-Versus-Host Disease (GVHD)

Onset

• Variable onset after transplant

Pathogenesis

• Immunocompetent donor T cells attack host tissues
• Seen when a graft rich in lymphocytes is transferred into an immunocompromised host
  → e.g., bone marrow, liver transplants
  → Type IV hypersensitivity

Key Features

• Host epithelial damage leading to:
  • Diffuse maculopapular rash
  • Diarrhea
  • Jaundice
  • Hepatosplenomegaly

Clinical notes

• Increased risk with HLA mismatch
• May be beneficial in leukemia (graft-versus-tumor effect)
• To prevent GVHD in transfusion-dependent patients → irradiate donor blood products

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Activity

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Key Summary Table