Most people think of organs like the heart, kidney, lung, and liver when they think of transplants, but skin grafting is just as common in the medical field. Skin grafting is the transplantation of skin to another part of the body. Skin harvesting and transplantation techniques began nearly 3000 years ago with the Hindu Tilemaker Caste, where they used skin grafting to rebuild noses that were cut off from judicial punishment (Grande & Mezebish, 2008). In the mid 1900s, rodents were used to study skin grafting techniques in the name of medicine (Abbas & Lichtman, 2009).
Now-a-days, skin grafting is a very common dermatologic surgery. It can be used for burn victims with thinned tissues, to cover cutaneous ulcers that won’t heal, to restore areas of hair loss, and to restore any area of defective skin (Grande & Mezebish, 2008). Skin grafting used to be very problematic because of the body’s negative immune response, but with advances in science and medicine, skin grafting techniques and acceptance have come a long way. The immune system functions to protect the body against actual or potential disease or illness.
Anything not recognized a part of the body it protects, causes the immune system to initiates steps to attack the foreign invader. This is a significant problem in terms of skin grafting. Identical twins are syngeneic because they have the exact same DNA, so skin grafting would not be a problem in that case (Abbas & Lichtman, 2009). With that said, most humans are allogeneic, meaning we differ even though we are of the same species (Abbas & Lichtman, 2009). Being that we differ, this causes graft rejection when skin graft transplantation is attempted.
The interesting thing about humans is that we express six class I Major Histocompatibility Complex (MHC) alleles and a minimum of six class II MHC alleles (Abbas & Lichtman, 2009). MHC genes are extremely polymorphic, so they can be inherited and expressed in numerous combinations (Abbas & Lichtman, 2009). What this means is that with the exception of twins, everyone expresses MHC proteins that are foreign to the next person. T cells are matured to only recognize peptides displayed by self MHC molecules, with all others being known as foreign.
So when skin grafting from donor to recipient, the immune response is to attack. Antibodies and T cells are the responders to the antigens and are said to be alloreactive (Abbas & Lichtman, 2009). T cells are typically the ones responsible for initiation of the immune response by direct recognition. This then stimulates the production of alloreactive T cells, also called CTLs, which recognize and attack graft cells (Abbas & Lichtman, 2009). Alloantigens can also be identified by indirect recognition.
In either case, the dendritic cells that impart alloantigens also provide costimulators that arouse helper T cells and CTLs. The only difference would be that with indirect recognition, they can’t recognize and kill graft cells because the CTLs are specific for alloantigens displayed by self MHC molecules, on antigen presenting cells of the host (Abbas & Lichtman, 2009). There are three mechanisms of graft rejection that are pretty important: hyperacute rejection, acute rejection, and chronic rejection.
Hyperacute rejection is a response that is evident within minutes of transplantation, and is distinguished by thrombosis of graft vessels and ischemic necrosis of the graft (Abbas & Lichtman, 2009). It is mediated by antibodies that are specific for antigens on graft endothelial cells. The antibodies bind to the antigens and activate the complement and clotting system, leading to damage of the endothelium and thrombus structure. Acute rejection takes place days or weeks later and is mediated by T cells that react against alloantigens in the graft.
When the vascular component is involved, it is more likely that antibodies are the mediators. Chronic rejection is graft damage that occurs months or even years down the road. This can be disheartening because it is a progressive loss of graft functioning. It is manifested as fibrosis of the graft and arteriosclerosis. In this case, the T cells respond to graft alloantigens by secreting cytokines that initiate production and behaviors of fibroblasts and vascular smooth muscle cells within the graft (Abbas & Lichtman, 2009).
The solution to it all has been immunosuppressive drugs. Cyclosporine has primarily taken the lead of the immunosuppressive drugs (Abbas & Lichtman, 2009). It works by blocking T cell phosphatase, which is required to activate the transcription factor Nuclear Factor of Activated T cells (NFAT) (Abbas & Lichtman, 2009). This stops the transcription of cytokine genes in the T cells, but also inhibits other natural responses, which then makes the person very susceptible to infections.
In years to come, the goal would be to be able to suppress the immune system for the graft alloantigens specifically, so that the rest of the immune system is able to respond to other invaders. Experiments are currently underway, but there is a great deal of respect for the successes that have already been achieved. References Abbas, A. & Lichtman, A. (2009). Basic immunology. Philadelphia, PA. Saunders Elsevier. Grande, D. J. & Mezebish, D. S. (October, 2008). Skin Grafting. Retrieved May 21, 2010, from http://emedicine. medscape. com/article/1129479-overview