From Arthritis to Zoster

Our daughter got her driver’s license yesterday. As she completed the requisite forms, she checked the box that designated her as an organ donor. But it wasn’t just a matter of ticking the square and moving on. In our state, a resident can opt to donate any needed body part or limit donation to specific organs or tissues; one can prohibit the use of an anatomical gift for certain purposes (i.e., therapy, research, or education); and one’s gift of tissues or organs can be limited to use only by non-profit procurement entities (i.e., the nearest “organs-for-sale” outlet cannot harvest your body parts).

If that whole process seems a bit convoluted, its complexity pales in comparison to the organized chaos that befalls a donated organ in the unfortunate event of a driver’s death. Before an organ or tissue takes up residence in another human being, its compatibility for its new home must be determined.

To simplify a very intricate process isn’t always easy, particularly when the only language available to describe it is rooted in scientific jargon; relatives who voluntarily donate tissues for loved ones often get mired in the “technospeak” that surrounds organ donation. Hence, it’s worth the effort to clarify the methodology – and the underlying science – that surrounds organ and tissue transplantation.

The Major Histocompatibility Complex and the Human Leukocyte Antigen System

Every human being possesses a unique combination of immunologic markers that coat the surfaces of their cells. Like fingerprints, these markers help each person’s immune system differentiate what is “us” from what is “not us.” These markers – they’re like molecular Braille protruding from a cell’s membrane – consist of long protein-like molecules that our immune cells can read and recognize.

A cell’s machinery for producing these markers is located on one chromosome (chromosome 6, for those who are interested); hence, every cell that has a nucleus – or that ever had a nucleus – possesses its own allotment of markers. The impressive array of markers that can be generated among the human population arises from variations in the genes — called the major histocompatibility complex (MHC) – which reside within a small region on this single chromosome.

Many animals possess a MHC (it’s one of the things that differentiates one species from the next); in humans, the various types of genes that represent the MHC are collectively called the human leukocyte antigen (HLA) system.

Yes, it’s complicated, but let’s continue wading together, and we’ll eventually get to dry ground.

It is the job of the MHC to present specific markers to our leukocytes – specifically, our T lymphocytes – so immune integrity can be maintained and all foreign antigens (things that are “not us”) can be eliminated. Two major types of MHC markers have been described:

1. Class I MHC markers are present on the surfaces of all nucleated cells and platelets. These markers are generated from HLA genes at three different locations on chromosome 6. T lymphocytes that recognize class I markers tend to be CD8 (cytotoxic) cells. CD8 cells are instrumental in killing other cells that are infected with viruses or those whose markers have changed (i.e., cancer cells)
2. Class II MHC markers are found on the surfaces of cells that present antigens to other immune cells: B cells, macrophages, NK cells, dendritic skin cells, and Langerhans’ cells “capture” antigens that are present within their respective environments and “show” them to immune cells that can either confirm the antigens as “self” or initiate the immune cascade that eventually destroys a foreign invader.

Other types of MHC markers – mostly inflammatory molecules – also exist, but class I and II MHC markers play the lead roles in immune compatibility.

Whenever a tissue or organ is introduced to an immune system that recognizes it as a foreign antigen, that tissue or organ will be promptly rejected. “Near misses” – transplants whose MHC markers match most of the recipient’s markers – can often be tolerated if the recipient’s immune system is suppressed with medications, but any tissue with too many disparate markers cannot be safely transplanted.

In summary, then, HLA testing is used to determine if a donated organ or tissue will match the immune system of someone who needs a transplant. HLA compatibility is essential if a transplanted organ is to survive within the recipient; conversely, HLA incompatibility usually signifies that the potential recipient must wait for a different donor.