How the Immune System Impacts Organ Transplantation

Medically reviewed by Jennifer Schwartz, MD

To understand how and why organ rejection after transplantation happens it is important to understand not only the organ transplant process, but also some essential information about the immune system, different types of organ donors, and how these two things can complicate organ transplantation.

What Is a Transplant?

A transplant is a medical procedure where tissue or an organ is removed from one body and implanted into another body to replace an organ or tissue that is not functioning well, is absent, or diseased.

Organ transplantation is only done for severe disease. This process is not done for mild or even moderate disease, it is done when an organ is so diseased that it will eventually lead to dialysis or death without a transplant.

The most common transplants are done by taking an organ from one human body, alive or deceased, and transplanted into another human body. Organs, tissues such as skin, ligaments, and tendons, and even the cornea from the eye can be recovered and given to a recipient to treat a wide variety of issues.

It is possible to transplant animal tissues as well, such as from a pig or a cow, and use it for a human recipient. One of the more common ways that this type of tissue can be used is for patients who need a heart valve replaced.

Historically, organs for transplantation have been taken from one human body and placed into another human body. There have been rare instances of organs being removed from a primate and placed into a human recipient. Of these, the most famous is the 1984 case of Stephanie Fae Beauclair, better known as “Baby Fae,” who received a baboon heart at the age of 11 days before dying of organ rejection at the age of 31 days.

Types of Transplants

There are multiple types of transplants and a long list of ways to describe the procedures that make transplants possible. The risk of rejection varies between types of donors, as the differences between donor and recipient can increase the chances of rejection. For that reason, understanding the nature of the transplant can help determine the risk of rejection and can even help the healthcare team decide how much medication is necessary to help prevent that rejection.

Here is a short list of terminology used for different types of transplants.

• Autograft: Tissue is taken from one part of the body and transplanted into another part of the same body. For example, after experiencing a severe burn, a patient may have a skin graft that is taken from their own leg. This improves the chances of the graft healing well, and rejection issues are virtually non-existent as the donor and recipient are the same individuals.

• Allograft: This type of transplant is a human to human transplant of tissues, organs, or corneas. The donor is a different human than the recipient and cannot be genetically identical (such as identical twins). There is a notable risk of rejection with this type of organ transplant.

• Isograft: This type of transplant is done between a genetically identical donor and a recipient, such as an identical twin. There is virtually no risk of rejection in this case, as the body does not recognize an identical twin’s organ as foreign.

• Xenograft: This type of transplant is between different species. This is a species to species transplant, such as baboon to human or pig to human. Typically, these are tissue transplants but in rare cases have been organ transplants. There is an expectation of significant risk with this type of organ transplant, but often tissue transplants offer the minimal risk of rejection.

Types of Organ Donors

There are three types of organ donors to note.

• Cadaveric Donor: A deceased donor’s tissues, organs, and/or corneas are transplanted into a living human recipient. This type of donation has the same level of risk as any other unrelated donor unless genetic testing determines the match between donor and recipient is better than typical.

• Living Related Donor: A living human donor donates an organ to a relative in need of an organ transplant. The transplant may be slightly less likely to be rejected due to genetic similarity between the donor and recipient.

• Altruistic Donor: A living donor chooses to give an organ to an unrelated recipient. This type of donation has the same level of risk of rejection as any other unrelated donor unless the donor and recipient are a particularly good genetic match.

Organ Rejection

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.

How the Immune System Works

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. The immune system is able to identify what is “self” and belongs in the body and can also identify what is “other” and fight it off.

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. The immune system doesn’t always keep things from entering the lungs or the bloodstream or from creating an infection, but it is extremely successful at fighting them off.

The immune system can also cause problems when it inaccurately sees “self” as “other.” This type of problem is referred to as “autoimmune disease” and is responsible for serious illnesses such as lupus, multiple sclerosis, ulcerative colitis, type 1 diabetes, and rheumatoid arthritis. These diseases are all caused by the immune system being triggered without good reason, and the results can be devastating.

The Immune System and Organ Rejection

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. That is typically done with medication, or many medications, that help trick the body into recognizing “other” as “self.” Put simply, the immune system needs to think that the new organ is part of the body, rather than an organ that doesn’t belong.

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.

Research is helping transplant patients win the war against transplant rejection, as well as graft versus host disease, by helping determine exactly how the immune system identifies the body and an organ as “other” after transplant. 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.

What Triggers Organ Rejection?

It is believed that the presence of the organ is initially identified as “other” when the SIRP-alpha protein binds to a microscopic receptor on a white blood cell. From there, a chain reaction occurs that can lead to full organ rejection if it isn’t caught in time or if medication is unsuccessful in controlling the reaction.

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.

Decreasing the Risk of Rejection Before Transplantation

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.

If the donor is a living donor, a relative is often preferred because the chances of rejection are decreased. We may find in the future that this is because families have better SIRP-alpha matching, but at this time that is just one theory.

Genetic testing is also done to make the best possible donor-recipient match. This is especially important with kidney transplants, as the best matches result in significantly more years of organ function.

Expect to see research that helps make better pairings between donor and recipient genetics, as well as more research into selectively “turning off” parts of the immune system to prevent rejection.

Decreasing the Risk of Rejection After Transplantation

Currently, after an organ transplant has been completed, the patient’s lab results and the type of transplant will help dictate the type of medication and the amount of medication that is given to prevent transplant rejection.

Labs will be frequently monitored in the weeks and months after the transplant, and then the frequency decreases for most patients after the first year. Still, the patient will be taught to look for signs of rejection and to be vigilant about maintaining their health.

Watching for rejection, adjusting medications based on the threat or actual presence of rejection, and retesting is common. This is done to determine if the rejection episode has resolved is a routine transplant recipient must deal with in order to maintain their health.

In the future, as more progress is made in the suppression of the immune system, patients may require less medication, less monitoring, and experience better long-term transplant health. That said, research should lead to more effective medications that are able to stop rejection from occurring or can stop the progress of rejection once it is discovered.