MORPHOLOGYAcutecellular(Tcell-mediated)rejectionmayproducetwodifferentpatternsofinjury.
Inthetubulointerstitial pattern (sometimescalledtypeI),thereisextensiveinterstitialinflammationandtubularinflammation(tubulitis)associatedwithfocaltubularinjury(
Fig.5.32B ).Asmightbeexpected,theinflammatoryinfiltratescontainactivatedCD4+ andCD8+ Tlymphocytes.
Fig.5.32C )andsometimesnecrosisofvesselwalls(typeIII).Theaffectedvesselshaveswollenendothelialcells,andatplaceslymphocytesareseenbetweentheendotheliumandthevesselwall,afindingtermedendotheliitis orintimal arteritis.Therecognitionofcellularrejectionisimportantbecause,intheabsenceofaccompanyinghumoralrejection,mostpatientsrespondwelltoimmunosuppressivetherapy.
In acute antibody-mediated (vascular or humoral) rejection, antibodies bind to vascular endothelium and activate complement via the classical pathway (
Fig. 5.33A ). The resultant inflammation and endothelial damage cause graft failure.
MORPHOLOGYAcuteantibody-mediatedrejectionismanifestedmainlybydamagetoglomeruliandsmallbloodvessels.Typically,thereisinflammationofglomeruliandperitubularcapillaries(
Fig.5.33B )associatedwithdepositionofcomplementproducts,whichisduetoactivationofthecomplementsystembytheantibody-dependentclassicalpathway(
Fig.5.33C ).Smallvesselsalsomayshowfocalthrombosis.
• Chronic rejection is an indolent form of graft damage that occurs over months or years, leading to progressive loss of graft function. Chronic rejection manifests http://ebooksmedicine.net
Recruitment of macrophages and neutrophils
Fig. 5.32 Acute cellular rejection. (A) Destruction of graft cells by T cells. Acute T cell–mediated rejection involves direct killing of graft cells by CD8+ CTLs and inflammation caused by cytokines produced by CD4 T cells. (B) Acute cellular rejection of a kidney graft, manifested by inflammatory cells in the interstitium and between epithelial cells of the tubules (tubulitis). Collapsed tubules are outlined by wavy basement membranes. (C) Rejection vasculitis in a kidney graft. An arteriole is shown with inflammatory cells attacking and undermining the endothelium (endotheliitis) (arrow). (Courtesy of Drs. Zoltan Laszik and Kuang-Yu Jen, Department of Pathology, University of California, San Francisco, California.) as interstitial fibrosis and gradual narrowing of graft blood vessels (graft arteriosclerosis). In both lesions, the culprits are believed to be T cells that react against graft alloantigens and secrete cytokines, which stimulate the proliferation and activities of fibroblasts and vascular smooth muscle cells in the graft (
Fig. 5.34A ). Alloantibodies also contribute to chronic rejection. Although treatments to prevent or curtail acute rejection have steadily improved, leading to longer than 1-year survival of transplants, chronic rejection is refractory to most therapies and is becoming the principal cause of graft failure.