Graft-versus-host disease

With “graft-versus-host disease”, “graft” refers to a section of transplanted, or donated tissue, like bone marrow or peripheral blood, and “host” refers to the tissues of the person receiving the transplant.

In graft versus host disease, immune cells in the donated tissue attack the recipient’s body cells.

Normally, the immune system’s job is to fight against anything foreign that might cause harm, without harming the body’s own cells.

To make that work, the immune system cells are trained, from early on, to distinguish non-self or foreign, from self.

Recognizing whether a cell is non-self or self involves a set of genes called histocompatibility genes, which make up the major histocompatibility complex, or MHC proteins.

These MHC proteins also go by the name human leukocyte antigens, or HLA.

The histocompatibility genes actually code for two classes of proteins, MHC class I and MHC class II.

MHC class I molecules are found on all nucleated cells throughout the body, while MHC class II molecules are only expressed on antigen presenting cells like monocytes, macrophages, dendritic cells, and B cells.

But because the genes coding for them are so variable in the population, two different individuals will have major differences in the antigens expressed on their cells, even siblings - unless, of course, they’re identical twins.

When there’s a tissue transplantation, the transplant usually comes from a genetically different individual, and it’s called an allograft.

If there are immune cells within that allograft, they will see the MHC proteins that coat every cell of the recipient body as “non-self”.

In fact, that’s why transplantation donors are really carefully selected, to make sure that they share as many of the same HLA antigens with the host as possible.

But even between HLA-identical individuals, other antigens, called minor histocompatibility antigens, can be recognized as foreign and trigger an immune response between the donor and the recipient.