Section 3 Transplant Rejection Section 3 Transplant Rejection

1. 1. Terms:Terms:

AutograftAutograft: transplantation within the same

individual

Isograft or syngeneic graftIsograft or syngeneic graft: between identical

twins or inbred animals

AllograftAllograft: between individuals of the same species

but of differing genetic make-up

XenograftXenograft: between different species.

2. 2. Types of rejectionTypes of rejection

(1) (1) Superacute rejection:Superacute rejection:①TimeTime: within minutes or hours after transplantation.

②CausesCauses: these are major incompatibility with high levels of humoral antibodies.

③MorphologyMorphology: a. thrombotic occlusion of the capillaries b. Fibrinoid necrosis occurs in arterial walls. c. Infarction d. Neutrophils infiltrating

(2) (2) Acute rejectionAcute rejection

① ① Time: Time:

Within days to weeks in the untreated Within days to weeks in the untreated recipient. Or may appear suddenly recipient. Or may appear suddenly months or even years later, when months or even years later, when immunosuppression has been immunosuppression has been employed. employed.

② ② Types:Types:

a. Acute cellular rejection: diffuse mononuclear cell infiltrating that may invade the tubules, causing focal tubular necrosis, and edema as well as mild interstitial hemorrhage.

b. Acute rejection vasculits (humoral rejection): necrotizing vasculitis with endothelial necrosis, neutrophils infiltration, deposition of immunoglobulins, complement, and fibrin, and thrombosis the vascular intima is markedly thickened and inflamed.

Slide 7.20

Schematic representation of the events that lead to the destruction of histoincompatible grafts. Donor class I and class antigens along with B7 Ⅱmolecules are recognized by CD8+ cytotoxic T cells and CD4+ helper T cells, respectively, of the host. The interaction of the CD4+ cells with peptides presented by class antigens Ⅱleads to proliferation of TH1-type CD4+ cells and the release of interleukin 2 (IL-2) from the cells. IL-2 further augments the proliferation of CD4+ cells generates a variety of other soluble mediators (lymphokines) that promote B-cell differentiation. The TH1 cells also participate in the induction of a local delayed hypersensitivity reaction. Eventually, several mechanisms converge to destroy the grafe: (1) lysis of cells that bear class I antigens by CD8+ cytotoxic T cells, (2) antigraft antibodies produced by sensitized B cells, and (3) nonspecific damage inflicted by macrophages and other cells that accumulate as a result of the delayed hypersensitivity reaction.(From Robbins Basic Pathology ,2003 ）

Slide 7.21

Acute cellular rejection of a renal allograft. A, An intense mononuclear cell infiltrate occupies the space between the glomerulus (bottom left) and the tubules. B, Tubule, highlighted by the basement membrane, undergoing destrction by invading lymphocytes. (Dr. Ihsan Housini)

(From Robbins Basic Pathology ,2003 ）

Slide 7.22

Antibody-mediated damage to the blood vessel in a renal allograft. The blood vessel is markedly thickened, and the lumen is obstructed by proliferating fibroblasts and foamy macrophages. (Dr. Ihsan Housini) . (From Robbins Basic Pathology ,2003 ）

(3) (3) Chronic rejectionChronic rejection

① Time: months——years ② Morphology:

Vascular changes consist of dense intimal fibrosis;

Interstitial fibrosis, tubular atrophy, shrinkage of the renal parenchyma;

Mononuclear cell infiltrates containing large numbers of plasma cell and numerous eosinophils.

It occurs in any situation in which immunologically component cells or their precursors are transplanted into immunologically crippled recipients.

(4) Graft-versus-host (GVH) disease:Graft-versus-host (GVH) disease:

3. 3. Methods of increasing graft survivalMethods of increasing graft survival

(1) Favourable sites for transplantation

① cornea and anterior chamber of the eye

② meninges

③ testis

(2) Accurate tissue matching(3) Immune deficiency states, pregnancy,

and uraemia(4) Immunosuppression ① Corticosteroids ② Azathioprine ③ Antilymphocyte serum ④ Whole-body irradiation ⑤ Induction of immune tolerance