The majority of transplants done in the United States are actually tissue transplants. These transplants may be bone, ligaments, tendons, heart valves, or even skin grafts. For these recipients there is some very good news: they are far less likely to experience rejection of these tissues.
For organ recipients, rejection of the new organ is an issue of such significance that it requires frequent monitoring through blood work, daily medication, and significant expense.
Rejection means that the body rejects the new organ because it sees it as a foreign invader similar to an unwanted infection. The possibility of rejection is often a constant worry for transplant recipients because rejection could mean returning to dialysis treatments or even death due to organ failure. The immune system is complex and very complicated, and in most cases does an amazing job of keeping the human body well.
The immune system does many things, protecting the body from viruses, germs, and diseases as well as helping the healing process. To say that the immune system is complex is truly an understatement, as entire textbooks are written on the immune system and how it protects the body.
Without the immune system, we would not survive infancy as we would be unable to fight off the most minor bacteria—exposure to even a cold could lead to death. This system is usually very effective in keeping an individual well and keeping the bad stuff out of the body, or fighting it off when it does enter the body.
These diseases are all caused by the immune system being triggered without good reason, and the results can be devastating. In the case of organ transplants, the greatest challenge—after locating an organ that is appropriate for transplantation—is to keep the new organ healthy by preventing rejection.
Tricking the immune system is more challenging than it might seem because the body is very good at identifying invaders because it is essential to life. In most people, the immune system becomes more adept and stronger during the first decades of life and is better able to fight off infection with each passing year well into adulthood. Finding out exactly which part of the immune system starts the many steps in rejection means that eventually a way to prevent it can be created.
Researchers theorize that like blood types, there will be SIRP-alpha types, and by testing the donor and the recipient they could reduce the risk of transplant rejection before surgery is done by matching donor and recipient SIRP-alpha types. This could reduce the overall risk of rejection, decrease the amount of medication needed to prevent rejection, and most of all, help the organ last longer in the recipient.
There are already multiple ways that the chance of rejection is decreased before surgery, first and foremost by making sure the recipient and the donor have compatible blood types, then moving on to more sophisticated testing and techniques.
Normally, foreign entities are seen as threats, and in the case of viruses, bacteria, or parasites, this is a good thing! Recognizing and destroying infection quickly prevents you from developing serious symptoms. In the case of transplants, we must trick the immune system into tolerating a foreign object in the body. While tissue rejection is quite uncommon, there is still a low risk of rejection when it comes to organ transplants. Human to human islet transplants are already sometimes used to treat patients but due to a shortage of donors, scientists are interested in developing animal sources of the tissue.
Even human — human islet cell transplants would be more successful if ways could be found around the immune system mediated rejection of the transplanted tissue. Transplanted tissue from another human contains molecules called antigens which are recognised by T-cells as foreign. These antigens are usually carried to T-cells by antigen presenting cells APCs such as macrophages which have come into contact with the donor tissue.
To elicit an immune response this must be combined with a second event called costimulation, whereby other T-cells or APCs stimulate the T-cell, this ensures the response is regulated.
The T-cell then replicates and differentiates to produce large numbers of cytotoxic T-cells that are primed to recognise the foreign tissue and attack it by releasing enzymes that cause the donor tissue cells to commit suicide in a process called apoptosis. A second, less common, cause of tissue rejection is the humoral response, mediated by antibodies. B-cells become activated and produce antibodies in response to contact with antigens of the transplanted tissue and in the presence of activating T-helper cells or APCs.
They replicate and secrete antibodies that bind to the foreign tissue acting as a tag to signal to cytotoxic T-cells and phagocytes — large cell-eating cells — to attack the donor tissue. A new technique described in Diabetes uses a two-step process to trick the immune system.
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