The Fate Of Allografts

Allografts are usually rejected in one of three patterns: acute rejection; accelerated and hyperacute rejection; and chronic rejection.

Acute Rejection

Around 5-7 days the tissue begins to manifest signs of two processes: inflammation and specific cell injury. The inflammation is manifested by infiltration with mononuclear cells, accompanied by edema and reduced blood flow; specific destruction of parenchymal and endothelial cells by infiltrating lymphocytes, coupled with decreased perfusion, cause a rapid loss of function. Destruction of blood vessels frequently leads to late infarction of some or all of the tissue.

Accelerated and Hyperacute Rejection

If certain organs, particularly kidneys, are transplanted into a recipient who has high levels of preformed antibodies against donor alloantigens of the graft endothelium, particularly HLA class I (see below) or ABO blood group antigens, hyperacute rejection follows. The antibodies on the endothelium fix complement, which attracts polymorphs, and destroy the endothelium within hours or even minutes. Hyperacute rejection is usually prevented by "crossmatching", i.e., testing the recipient's serum for complement-dependent antibodies against donor lymphocytes.15

Organ Transplantation, 2nd edition, edited by Frank P. Stuart, Michael M. Abecassis and Dixon B. Kaufman. ©2003 Landes Bioscience.

Table 1.1. Outline

Table 1.1. Outline

I. The Fate of Allografts

II. The Principal Molecules of Allorecognition

III. T-Cell Recognition and Triggering

IV. Specific Immune Responses of T Cells and B Cells

V. Organization of Inflammation VI. Changes in the Target Issue

VII. Target Injury

VIII. Host and Graft Adaptation

IX. Chronic Rejection

Table 1.2. Classification of grafts according to origin

Autograft Tissue from one site to another in the same individual

Isograft Tissue from one individual to another with the same genotype (e.g., grafts between monozygotic twins)

Allograft Tissue from genetically disparate individuals from the same species

Xenograft Tissue from a different species (e.g., porcine cardiac valves)

If the recipient has previously been sensitized against donor antigen, e.g., by pregnancies, transfusions, or previous grafts, but does not have preformed antibodies in the circulation, rejection may occur around day two or three, earlier than typical acute rejection. This accelerated rejection is more vigorous, a reflection of specific immunologic memory for the antigens of the graft. It is mediated by the rapid return of high levels of specific T cells and/or alloantibody directed against the antigens of the graft.

Chronic Rejection

An initially successful transplant may gradually lose its function in a slow scarring process. The arteries become obstructed by intimal thickening, and the graft undergoes progressive parenchymal atrophy and interstitial fibrosis. Chronic rejection has been most studied in patients with renal and heart transplants, and can occur months to years after transplantation. In some cases it may be antibody-mediated, but typically no antibody is demonstrable and the pathogenesis is not understood.16 In heart transplants, the result is a potentially lethal form of diffuse obliteration of the medium and small coronary arteries, sometimes called graft atherosclerosis. In lung transplants scarring of the small bronchioles occurs (bronchiolitis obliterans) whereas in liver transplants the bile ducts are attacked (the vanishing bile duct syndrome).

Rejection is an immune response and the manifestations are attributable to molecules. We will now outline those molecules and how they lead to rejection.

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