Transplantation can be defined as the transfer of cells, tissues, or organs from one site in an individual to another, or between two individuals.In the latter case, the individual receiving the transplant is known as the recipient.
Organ transplantation has become a therapy to treat patients with end-stage disease. While many types of organs have been successfully transplanted, the histocompatibility barrier between recipient and donor remains a problem in that it will activate immune responses leading to graft injection.
The successful management of the transplant patient requires an understanding of the Major Histocompatibility Complex (MHC). A chromosomal segment that codes for cell surface histocompatibility antigens and is the principle determinant of tissue type and transplant compatibility. Also called HLA complex (human leukocyte antigen).
HLA molecules are identical between identical twins, but are otherwise different for every individual. They allow the body to distinguish "self" from "non-self". The ability to induce an immune response of transplantation antigens is so strong that differences between the antigens of the donor and recipient is enough to trigger an acute response.
HLA
HLA antigens are controlled by a series of genes on the short arm of chromosome 6, referred to as human MHC.
Different classes have different functions:
- class I antigens - patient peptides from inside the cell (including viral peptides if present)
- class II antigens - present phagocytosed antigens from outside of the cell to T-lymphocytes
MHC class I molecules are found on almost every nucleated cell of the body.
MHC lass II molecules are found only on a few specialized cell types, like macrophages, dendritic cells and B cells.
HLA Functions
The proteins encoded by HLAs are the proteins on the outer part of body cells that are unique to that person. The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying HLA type belongs to that person (and therefore is not an invader).
In Infectious Disease
When a foreign pathogen enters the body, special cells called antigen-presenting cells engulf the pathogen through phagocytosis. Proteins from the pathogen are digested into small pieces (peptides) and loaded onto HLA antigens (specifically MHC class II). They are then displayed for T cells, which then produce a variety of effects to eliminate the pathogen.
Through a similar process, proteins (both native and foreign, such as the proteins of viruses) produced inside most cells are displayed on HLA antigens (specifically MHC class I) on the cell surface. Infected cells can be recognized and destroyed by components of the immune system (specifically CD8+ T cells).
In Graft Rejection
Any cell displaying some other HLA type is "non-self" and is an invader, resulting in the rejection of the tissue bearing those cells. Because of the importance of HLA in transplantation, the HLA loci are strong among of the most frequently typed by serology relative to any other autosomal alleles.
In Cancer
Some HLA mediated diseases are directly involved in the promotion of cancer. Diversity of HLA in human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals having identical HLA molecules on all loci is very low.
Types Of Transplants
There are four basic types of transplants, which reflect the genetic relationship of the recipient to the donor.
1. The autograft is the transfer of tissue from one location of an individual's body to another location that is in need of healthy tissue; in other words, the recipient is also the donor. Common examples of autografts are skin transplants in burn patients.
2. The isograft is the transfer of tissue or an organ between two genetically individuals. These types of transplants like autografts, are always successful. The first successful human kidney transplant was carried out in 1954 between identical twins.
3. The allograft is the transfer of tissue or an organ between non identical members of the same species. This is the predominant form of transplantation today.
4. The xenograft is the transplant of organs or tissue from one species to another. Xenotransplantation is often an extremely dangerous type of transplant.
Transplant Rejection
Transplant rejection occurs when the immune system of te recipient of a transplant attacks tehe transplanted organ or tissue. This is because a normal healthy human immune system can distinguish foreign tissues and attempt to destroy them, just as it attempts to destroy infective organisms such as bacteria and viruses.
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