Transplantation

General Features

Transplantation refers to the engraftment of cells or tissues from one individual (donor) to another (recipient/host). Transfusion is a specific case of transplantation, using blood. Because a graft is foreign, the host's immune system will attempt to eliminate this "intruder", a phenomenon termed graft rejection (Fig. 17.1). For vascularized and nonvascularized (e.g., skin) grafts genetic differences at the major histocompatibility complex (MHC), are mostly responsible for graft rejection processes. Minor histocompatibility proteins with allelic forms can also induce graft rejection, with varying degrees of immunological "vigor". Current technology does not permit rapid determination of minor histocompat-ibility differences between donor and recipient, and the clinician is most concerned with the degree of MHC disparity involved.

The MHC encodes several cell surface proteins. In humans, class I MHC and class II MHC proteins are referred to as human leukocyte antigens (HLA). The existence of multiple MHC alleles in the population is referred to as polymorphism. Human class I MHC molecules are encoded by three loci (A, B, and C), whereas the class II MHC molecules are encoded by a "D" locus, subdivided into three loci, DP, DQ, and DR (Chapter 3). Each MHC allele is codominantly expressed, so individuals generally express six different class I MHC proteins, and six different class II MHC proteins, unless the parents were genetically related. Given MHC locus polymorphism and codominant expression of inherited MHC proteins of each class, most individuals have a pattern of MHC expression that differs from that present in other individuals, except in the case of identical twins.

Successful organ transplantation depends on suitable MHC matching and life long nonspecific immunosuppressive therapy. Because of the complications of nonspecific immunosuppression, specific tolerance induction to grafts remains an area of high priority in transplantation.

Classification of Grafts According to Their Source

Grafts are classified according to the source of the tissue donor (Fig. 17.2). Isografts are grafts between identical twins (autografts, e.g., skin, are grafts within the same individual); allografts are grafts between members of the same species; xenografts are grafts across species.

Since there is no genetic disparity in iso/auto grafts, engrafted tissue survives without the need for immunosuppression. Besides the use of organ and bone marrow grafts from identical twins, autografts (bone marrow) are used in rescue therapy for lymphoma and/or some other malignancies (e.g., breast cancer). Patients donate their own bone marrow (which is treated to "purge" it of residual malignant cells), then receive doses of chemotherapy which are "super toxic",

Fig. 17.1. Concept map illustrating graft rejection. Immune recognition and ischemia-reperfusion injury trigger the secretion of chemokines and cytokines, producing the inflammatory/immunological changes of graft rejection.

Graft Rejection

Activate Vascular Endothelial Cells To ,_i_

is initiated when

Surgical and Ischemic Perfusion | induces

Chemokine and Cytokine Secretion by Graft (Donor) Cells

Enter Circulation-

Express Adhesion Molecules /Activate them to High Affinity

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