Immunology · Transplant, tumors and immunotherapy
Transplant rejection: hyperacute, acute, chronic !
- Process
The body sees a donated organ as foreign and attacks it, within minutes, weeks or slowly over years.
Updated 2026-11-01
What it is
Rejection is the recipient's immune response against donor antigens, mainly HLA (MHC) molecules and ABO blood group antigens. Its timing tells the mechanism: preformed antibodies act in minutes, T cells and new antibodies act in weeks to months, and slow vascular and fibrotic damage builds over years. ABO matching, HLA typing, crossmatch tests and immunosuppressive drugs reduce the risk.
Key facts
- Graft types: autograft (self), isograft (identical twin), allograft (same species), xenograft (other species).
- Corneas are rarely rejected because they have no blood vessels.
- Rejection must be told apart from drug toxicity (calcineurin inhibitor nephrotoxicity) and infection (CMV, BK virus); a graft biopsy settles it.
Step by step
- Donor tissue carries HLA molecules that the recipient's T cells have never seen as self.
- Direct recognition: recipient T cells react to intact donor MHC on donor dendritic cells (drives acute rejection).
- Indirect recognition: recipient antigen-presenting cells process donor HLA and show it on their own MHC (drives antibodies and chronic rejection).
- Activated CD4 T cells release IL-2 and other cytokines; CD8 T cells kill graft cells.
- B cells make donor-specific antibodies that fix complement on the graft endothelium.
- Repeated injury leads to vessel narrowing, fibrosis and slow loss of function.
Types of rejection
| Type | Timing | Mechanism | Pathology | Outcome |
|---|---|---|---|---|
| Hyperacute | Minutes to hours | Preformed anti-ABO or anti-HLA antibodies, complement (type II) | Thrombosis of graft vessels, ischemic necrosis; graft turns mottled and cyanotic | Graft removed; prevented by ABO matching and crossmatch |
| Acute cellular | Weeks to months (most often in the first 6 months) | CD8 and CD4 T cells against donor MHC (type IV) | Lymphocytic infiltrate, tubulitis, endothelialitis | Usually reversible with steroids or T-cell–depleting antibodies |
| Acute antibody-mediated | Weeks to months, or later | New donor-specific anti-HLA antibodies, complement | Capillary inflammation, C4d staining | Treated with antibody-removal strategies; worse prognosis |
| Chronic | Months to years | T cells, antibodies and non-immune injury together | Intimal proliferation and fibrosis of vessels, parenchymal atrophy | Irreversible; main cause of late graft failure |
Test yourself
Think of the answer, then tap the question to see it.
What causes hyperacute rejection and how is it prevented?
Preformed antibodies against donor ABO or HLA antigens; it is prevented by ABO matching and a pretransplant crossmatch.
Which immune cells drive acute cellular rejection?
Recipient T cells (CD8 cytotoxic and CD4 helper) reacting against donor MHC molecules.
What biopsy marker suggests antibody-mediated rejection?
C4d deposits in the graft capillaries, a footprint of complement activation by antibodies.
What is chronic rejection of a lung transplant called?
Bronchiolitis obliterans (chronic lung allograft dysfunction).
See it in 3D
The structures of Durgical's 3D anatomy where it is found.
Related
- MHC/HLA class I and II
- Type II hypersensitivity (antibody against cells)
- Type IV hypersensitivity (delayed, T cells)
- ABO and Rh blood groups, hemolytic disease of the newborn
- Graft-versus-host disease
- Immunosuppressants by mechanism (classes)
Microorganisms
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: Transplant rejection (MedlinePlus, U.S. National Library of Medicine, 2026); Complement (MedlinePlus, U.S. National Library of Medicine, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.