Biology of Disease

owing to the increased genetic disparity between the donor and the recipi-

ent. Other more common examples of xenogeneic grafts involve the use of

porcine and bovine heart valves to replace diseased human ones. In the lat-

ter case the valves are treated with glutaraldehyde to stiffen them and to

mask their antigenic determinants, and these are often referred to as bio-

prosthetic valves. There is much debate about proposals to breed geneti-

cally engineered transgenic pigs to carry some human antigens on their

cells to provide transplants for humans. Apart from the ethics of breeding

animals purely to supply organs for humans, there is also the risk of the

transfer of an unknown virus from pigs to humans, with possible disastrous

consequences.

Causes of Graft Rejection

The transplanted cells of an allograft carry histocompatibility antigens on

their membranes, which are recognized as foreign by the cells of the immune

system. These histocompatibility antigens are found on proteins that are

encoded by the Major Histocompatibility Complex (MHC) which, in humans,

is also known as the Human Leukocyte Antigen (HLA) complex (Chapter 4).

The MHC complex is a genetic region that encodes several classes of proteins,

some of which are membrane proteins. Class I MHC proteins (MHC I) are found

on the membranes of all nucleated cells and are involved in the recognition

of virus-infected cells by the precursors of cytotoxic T lymphocytes (TCcells).

Class II MHC proteins (MHC II) are found on the membranes of antigen

presenting cells such as macrophages and are involved in the recognition by

TH lymphocytes of foreign proteins on the surface of antigen presenting cells.

It is relatively minor differences between the amino acid sequences of the

MHC molecules of the donor and of the recipient that lead to the rejection of

the transplanted tissue.

The rejection of an allograft usually takes place a few weeks after the trans-

plant unless immunosuppressive treatments are given. Small lymphocytes

recognize the transplanted cells as foreign. An acute rejection is caused by

T lymphocytes that infiltrate the graft. The presence of T lymphocytes and

monocytes in the infiltrate is a strong indicator of cell-mediated immunity.

Both TH and TC cells are involved in graft rejection. The TC cells develop into

cytotoxic T lymphocytes directed against the foreign histocompatibility anti-

gens of the grafted cells and are able to destroy cells of the grafts directly, or

indirectly by producing cytokines that attract monocytes and macrophages.

The TH lymphocytes respond by producing cytokines that activate a variety of

nonspecific cells to attack the graft.

Tissue organ transplanted Examples of clinical conditions

Bone marrow immune deficiency; in treatment of leukemia

Cornea types of blindness

Heart heart failure

Heart and lungs cystic fibrosis

Kidney end-stage renal failure

Liver cirrhosis

Pancreas type 1 diabetes mellitus

Skin treatment of burns

Table 6.12Tissue and organ transplants

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