STEPTRACKERGENERAL PRINCIPLES | IMMUNOLOGY + PATHOLOGY | HIGH-YIELD REVIEW

Transplant Rejection & GVHD

The recipient attacks the graft — or, in GVHD, the graft attacks the recipient. Timing names the type.

FOCUS ON
Order the types by onset. Hyperacute (minutes): preformed antibodies. Acute (weeks–months): T cells or new antibodies, often reversible. Chronic (months–years): vascular intimal thickening and fibrosis, irreversible. GVHD hits skin, liver and gut.
TYPE
MECHANISM
PATHOLOGY
CLINICAL CLUE
Hyperacute
minutes
Preformed recipient antibodies (ABO or HLA) bind graft endothelium → complement → thrombosis (type II).
Vessels thrombose; ischemic necrosis
Graft turns mottled and cyanotic on the table; prevented by crossmatch
Acute cellular
weeks–months
Recipient T cells (CD8 and CD4) recognize donor MHC, mainly by direct allorecognition.
Dense lymphocytic infiltrate; kidney: interstitial inflammation, tubulitis; endotheliitis
Rising creatinine, fever; reversible with steroids and immunosuppression
Acute antibody-mediated
weeks–months
New donor-specific antibodies attack graft vessels.
Vasculitis; C4d in peritubular capillaries
Treat with plasmapheresis, IVIG
Chronic
months–years
Ongoing T-cell and antibody injury, mainly indirect allorecognition (recipient APCs present donor peptides).
Intimal smooth muscle proliferation (graft arteriosclerosis), fibrosis, atrophy
Heart: coronary vasculopathy · lung: bronchiolitis obliterans · liver: vanishing bile ducts · kidney: fibrosis
Graft-versus-host disease
reverse direction
Donor T cells in the graft attack an immunocompromised host's tissues (type IV).
Apoptosis of epidermal, biliary and crypt epithelium
After BMT, liver transplant, non-irradiated blood: rash (palms, soles), jaundice, diarrhea
Graft-versus-tumor
the useful side
Donor T cells also kill residual leukemia cells.
—
Part of the benefit of allogeneic BMT
HLA matching
prevention
HLA-A, -B and -DR matter most; DR mismatch is the most damaging.
ABO compatibility + negative crossmatch required
Cornea rarely rejected (immune-privileged)
Post-transplant infection & cancer
cost of suppression
Suppressed T cells allow viral reactivation and EBV-driven B-cell growth.
CMV most common (1–6 months); EBV → PTLD
Fever, leukopenia, pneumonitis → CMV; new lymphoma → PTLD

Mechanism — who attacks whom

Graft placedDonor MHC exposed
→
Preformed AbHyperacute
→
T cells / new AbAcute
→
Smoldering injuryChronic fibrosis, vasculopathy
Graft rich in T cellsBMT, liver
→
Host can't rejectImmunosuppressed
→
GVHDSkin · liver · gut

Immunosuppressant snapshot

DRUG
TARGET
KEY TOXICITY
Cyclosporine
Calcineurin (cyclophilin) → ↓ IL-2
Nephrotoxic, gingival hyperplasia, hirsutism, HTN
Tacrolimus
Calcineurin (FKBP) → ↓ IL-2
Nephrotoxic, neurotoxic, diabetes
Sirolimus
mTOR → blocks IL-2 signaling
Cytopenias, hyperlipidemia; not nephrotoxic
Mycophenolate
IMP dehydrogenase → ↓ purines
GI upset, marrow suppression
Azathioprine
Purine antimetabolite
Marrow suppression (TPMT deficiency)
Belatacept · basiliximab
CD80/86 costimulation · IL-2 receptor
PTLD (belatacept); edema

How it's tested

COMMON CONFUSIONAcute rejection is reversible, chronic rejection is not. Chronic rejection looks like scarring and narrowed vessels, not a dense infiltrate.
THE TRAPA rash on the palms with diarrhea and jaundice weeks after a bone marrow transplant is GVHD, not a drug reaction or infection.
YOUR APPROACHTime since transplant → type. Then match the organ pattern (heart vessels, lung bronchioles, liver ducts) and the right treatment.

If you see… think…

Kidney turns blue minutes after the clamps come off → hyperacute rejection
Creatinine up at 3 weeks, lymphocytes in tubules → acute cellular rejection
C4d in peritubular capillaries → antibody-mediated rejection
Diffuse concentric coronary narrowing years after heart transplant → chronic rejection
Lung transplant, worsening obstruction → bronchiolitis obliterans
Palm rash, diarrhea and jaundice after BMT → GVHD
Fever, leukopenia, pneumonitis 2 months post-transplant → CMV
EBV-positive lymphoma after transplant → PTLD
Gum overgrowth and rising creatinine on transplant drugs → cyclosporine