Transplantation Immunology

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Basically, donor MHC molecule is handled like any other foreign antigen

Involve only CD4+ T cells.

Antigen presentation by class II MHC molecules.

Slide 9

Activation of Alloreactive T cells and Rejection of Allografts

Donor APCs migrate to regional lymph nodes and are recognized by the recipient’s TH cells.

Alloreactive TH cells in the recipient induce generation of TDTH cell and CTLs then migrate into the graft and cause graft rejection.

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Activation of Alloreactive T cells and Rejection of Allografts

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Role of CD4+ and CD8+ T Cells

CD4+ differentiate into cytokine producing effector cells

Damage graft by reactions similar to DTH

CD8+ cells activated by direct pathway kill nucleated cells in the graft

CD8+ cells activated by the indirect pathway are self MHC-restricted

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Role of Cytokines in Graft Rejection

IL – 2, IFN – , and TNF -  are important mediators of graft rejection.

IL – α promotes T-cell proliferation and generation of T – Lymphocytes.

IFN -  is central to the development of DTH response.

TNF -  has direct cytotoxic effect on the cells of graft.

A number of cytokines promote graft rejection by inducing expression of class – I or class – II MHC molecule on graft cell.

The interferon (α,  and ), TNF – α and TNF -  all increases class – I MHC expression, and IFN -  increases class – II MHC expression as well.

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Effector Mechanisms of Allograft Rejection

Hyperacute Rejection

Acute Rejection

Chronic Rejection

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Hyperacute Rejection

Characterized by thrombotic occlusion of the graft

Begins within minutes or hours after anastamosis

Pre-existing antibodies in the host circulation bind to donor endothelial antigens

Activates Complement Cascade

Xenograft Response

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Hyperacute Rejection

1. Preformed Ab, 2. complement activation,

3. neutrophil margination, 4. inflammation,

5. Thrombosis formation

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Acute Rejection

Vascular and parenchymal injury mediated by T cells and antibodies that usually begin after the first week of transplantation if there is no immunosuppressant therapy