Immunologie Aspects of Transplantation

I. HISTOCOMPATIBILITY, Rejection of grafts is antigenically specific and is determined primarily by allogeneic differences in the histocompatibility antigens [i.e., human leukocyte antigens (HLAs)]. The genes for the HLAs are located in the major histocompatibility complex (MHC) on chromosome 6.

A. HLA function. HLAs have two functions:

Their major physiologic function is to bind and present processed, foreign antigenic peptides to T cells, thus initiating the immune response (see Chapter 5).

2. They also artificially distinguish the membrane antigens on the transplanted donor organ from those of the recipient, provoking an attack by the recipient's sensitized T cells.

B. HLA classification. Class I and class II HLA genes, which encode antigens, exhibit enormous polymorphism, inasmuch as multiple different alleles exist at each locus.

1. Class I antigens are found on all nucleated cells.

a. Structure. Class I antigens have three gene loci: HLA-A, HLA-B, and HLA-C.

b. Identification. These antigens are defined serologically with anti-HLA antibodies. C. Function. Class I antigens present foreign antigenic peptides to CD8+ cells.

2. Class II antigens are found on immunologic effector cells (e.g., macrophages, B cells, activated epithelial cells).

a. Structure. Class II antigens have three gene loci within the D region: HLA-DP, HLA-DQ, and HLA-DR.

b. Identification. These antigens are defined by cellular reactions.

C. Function. Class II antigens present foreign antigenic peptides to CD4+ cells.

C. Tests for histocompatibility. Matching the donor and recipient at the HLA locus improves graft acceptance (Table 11-1).

1. Both donor and recipient are typed for HLA profiles using DNA sequence analysis of the HLA genes or more than 200 specific anti-HLA antisera.

2. Both donor and recipient are typed for ABO and Rh antigens with specific antisera.

3. The donor must be tested for preexisting anti-HLA antibodies and cell-mediated immunity (CMI) because sensitization to HLA antigens can occur as a result of prior blood transfusions, pregnancy, or other organ grafts. One way to test for preexisting anti-HLA antibodies and CMI is with a mixed lymphocyte culture.

a. Procedure

(1) Blood lymphocytes from the donor and the recipient are cultured together, and tritiated thymidine is added.

(2) The donor cells are treated with an antimitotic agent; therefore, any response can be attributed to the recipient's reaction against the donor's cells.

Table 11-1.

Types of Grafts

Type

Condition

Fate

Autograft

Within the confines of one's own self

Accepted

Isograft

Between members of an inbred species

Accepted

Allograft

Between members of a species (humans)

Rejected

Xenograft

Between members of different species

Rejected

Homovital

Viable, functional graft required

Homeostatic

Nonviable graft, used for support

(1) If the lymphocytes are antigenically incompatible, DNA is synthesized, and the cells divide.

(2) The extent of the genetic disparity can be determined by scintillation counting.

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