Transplant Rejection Is Like Your Dog Attacking Your Visiting Girlfriend

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Transplant rejection is a common but undesirable outcome of organ transplantation. The rejection is caused by the immune system. Your immune system accepts self-tissues but rejects anything foreign including viruses, bacteria, protozoa, and fungi among other antigens.

Unfortunately, the transplanted organ is also foreign and will be fought in the same manner as the listed types of antigens above. But this will be a disaster because getting a donor for an organ donation does not come easily.

An analogy of Transplant rejection

We know that everyone is very happy when they say that they go for years without going to the hospital or taking medicine. You feel so proud to put across such a statement to anyone who cares to listen, isn’t it? I do the same and feel very good as well.

The reason for such success is because of the strength of your immune system. When it’s working perfectly, it will always defeat foreign attackers. In the same way, your dog will not let anyone from outside disturb your peace at your home. They will be attacked ruthlessly. And you certainly feel protected.

Though you are happy when your immune system is attacking anything foreign, you wouldn’t want it to attack and eliminate your newly transplanted kidney (Foreign). It’s a precious gift that you cannot afford to lose. You can’t imagine going back to dialysis thrice a week. It’s costly, it’s time-consuming, and an uncomfortable affair. Is this then not what they call double standards on your part?

In the same way, you are happy when your dog deals with all trespassers at your home. But you don’t want to hear screams outside your house only to find your sweetheart (Visiting girlfriend) wrestled to the ground by your dog. You would feel so bad. Double standards again, isn’t it? Yes, no problem you’re just human. We like when things work the way we want not necessarily being always constant.

Types of Grafts (Transplants)

Autograft

This is a type of transplant where the graft (Organ or tissue) is transferred from one part of your body to another. For instance, you have an injury that disfigures your face. The doctors may decide to take some flesh from hidden parts of your body to reconstruct your face.

This will make you look more appealing courtesy of the science of transplantation, right? The fact that this graft is your own, means, your immune system will not fight it. It is the safest type of graft without any chances of transplant rejection at all.

Isograft

Isograft is a type of transplant that is obtained from a genetically identical individual. This could be a monozygotic twin brother or sister. This type of transplant is the second most successful after autograft. Your immune system will not perceive this type of graft as foreign and so it won’t fight it.

Therefore, the chances of transplant rejection are also minimal here. For instance, if you need a kidney transplant and you have a twin brother or sister, it is far safer to receive a kidney transplant from that twin than any other of your siblings or parents. Makes sense? It should.

Allograft

Allograft is a transplanted tissue from a genetically different individual but from the same species of animals. These are the commonest types of grafts in medical practice today.

The success of this type of graft is determined by how best the matching of the major histocompatibility complex (MHC) molecules between the donor and recipient is done.  MHC molecules happen to be on nearly all nucleated cells of your body. They are believed to be the most polymorphic (Genetically diverse) molecules in your body.

Therefore, if they can match between two individuals, then that means the immune systems of the two fellows will see them as very close to self-MHC and hence no transplant rejection.

Xenograft

These grafts are the most readily rejected transplants by the immune system. A xenograft is a graft from a source that is genetically different from the recipient, in that the individuals come from different species. For instance, a graft from a sheep to a human being would be a xenograft.

Transplant rejection is almost certain in this type of graft. The only time that the chances of rejection could be low is when the graft is of an immunologically privileged site like the brain or the eyes. In these sites, the immune cells rarely have access.

Clinical Stages of Transplant Rejection

Transplant rejection is manifested in different ways depending on what arm of the immune system is involved in the reaction. The rejection can be hyperacute, acute, or chronic. None is desirable because they all mean one thing. Possibility of losing your transplanted organ.

Hyperacute Transplant rejection

This type of transplant rejection occurs nearly immediately after transplantation.  This could be within a few minutes or hours. The reason for this reaction is that the developing new blood vessels (vascularization) are destroyed by your immune system.

This type of transplant rejection is caused by the humoral arm of the immune system. This means that the rejection reaction is mediated by antibodies that could be preexisting in your blood. These antibodies may be because of prior blood transfusion, prior transplantations, or multiple pregnancies.

The other arm of the immune system that may be involved in the rejection is the complement system. Through the classical pathway, the antigen-antibody complexes will activate the complement system. This may cause massive thrombosis inside your blood vessels. The vascularization of the new organ will further be hampered as a result.

Research has demonstrated that kidney transplants are more prone to hyperacute rejection than liver transplants. Though the reason for this is not very well known, it is hypothesized that the liver may be more resistant to rejection because of its dual blood supply.

Acute Transplant Rejection

Acute transplant rejection occurs after about 6 months. This rejection may be a humoral or cellular rejection. Whichever way, it’s rejected and it will destroy the transplanted organ.

Cellular rejection is mediated by the lymphocyte of your immune system. The lymphocytes involved here are the T lymphocytes. The T lymphocytes are regular visitors of the lymphoid organs (e.g., lymph nodes) whenever there are foreign antigens. In the lymphoid organs, they will be activated against the donor antigens and subsequently destroy them.

Humoral rejection on the other hand is mediated by antibodies. Antibodies are produced by your B cells. These antibodies may be produced after the transplantation, or they may be preexisting in your blood system before the transplantation.

Chronic Transplant Rejection

This type of transplant rejection may come several months to years after transplantation. The acute rejection episodes may even have subsided, and you nearly concluded that all was well. Chronic transplant rejection may be mediated by either T cells, antibodies, or both. This tells you about the intensity of this transplant rejection reaction.

Chronic transplant rejection manifests as fibrosis and scarring on the graft. This presentation can be massive. But there are other presentations depending on the type of organ involved. For instance, heart transplants may show accelerated atherosclerosis in the coronary arteries while kidney transplants may show allograft nephropathy.

Measures to Minimize Transplant Rejection

The value of transplantation cannot be over-emphasized. It is one medical breakthrough that has given many terminally ill patients a second chance to live. Transplant rejection should be anticipated and averted whenever possible.

There are several measures that have been employed to prevent transplant rejection. Many of them have been shown to be valuable. We shall now highlight some of those measures here:

ABO Blood Group Compatibility Testing

An individual with one type of blood group usually has corresponding antibodies to the other groups they don’t have in their blood. This is what we mean. For instance, a person with blood group A will have anti-B antibodies in their blood circulation. If such a person was transfused with blood group B, they would have a massive hemolytic reaction that would cause severe anemia.

Based on this understanding then, the first step in averting the possibility of transplant rejection is ensuring that the ABO and the rhesus blood groups are perfectly matched. This should be done even before you can do other tissue compatibility testing. If no match in the ABO blood group, that may mean everything else may not match.

Lymphocytotoxicity Assays

This is another test that is necessary to help in deciding whether transplantation should be attempted or not. In this test, your blood serum (the liquid part of the blood) is reacted with the donor lymphocytes in the laboratory.

If there is a positive reaction in-vitro (Outside the body) that means the same is likely to happen in-vivo (inside your body) as the recipient of the tissue or organ to be transplanted. Therefore, a positive reaction here is indeed a contraindication for transplantation.

If the doctors went ahead despite a positive reaction in this assay, you would have a hyperacute rejection reaction especially if the organ involved is a kidney. This is a situation you wouldn’t even want to imagine, isn’t it? But luckily, most doctors guided by medical ethics cannot attempt such a practice.

Panel-reactive antibody (PRA) Screening

To improve the chances of survival of a graft, this type of test is very important. In this test, serum from your blood as the recipient of the organ is screened for donor-specific anti-lymphocytic antibodies. A positive reaction is a contraction for the planned transplantation.

If you’ve had multiple blood transfusions before, there is an increased risk of a reaction because you may have been exposed to antigens like those of your potential donor being tested alongside you.  

The antibodies raised against such antigens will attack your new organ and hence the need for halting the planned transplantation and looking for another donor in such a case.

Mixed lymphocyte reaction (MLR)

In this type of reaction, the compatibility of MHC molecules of the donor and the recipient are tested. Remember we stated earlier that a perfect match of these molecules should be a must.

The compatibility of both MHC class I and MHC class II molecules is tested. Here, a positive reaction (for mismatch) should inform halting the entire plan and trying to identify another potential donor.

On the other hand, the perfect match is a green light for the transplantation surgery to be conducted. Such tests underscore the place of immunology in transplantation science.   

Immunosuppression To Minize Transplant Rejection

Immunosuppression is initiated immediately after transplantation to minimize the chances of a rejection reaction. It might sound like a great thing to suppress the immune system to avert a possible transplant rejection. Well, it is, if such an outcome is achieved.

But I must remind you that the other regular causes of disease like viruses, bacteria, protozoa, fungi, and others will not go on ‘leave’ while your immune system is suppressed. In fact, they might become opportunistic and decide that this is the best time to strike. Therefore, during immunosuppression, you become more vulnerable.

Examples of Immunosuppressive Drugs

There are many types of immunosuppressive drugs that can be administered to transplant patients. Some minimize inflammation that is triggered by transplantation. An example of an anti-inflammatory drug is corticosteroids.

Some drugs like the immunophilin-binding agents (e.g., Cyclosporine and Tacrolimus) suppress the activities of lymphocytes thereby reducing the chance of transplant rejection. Sirolimus is also another drug that inhibits signaling through IL-2 and hampers the activities of both B cells and T cells.

The latest scientific efforts have seen scientists raise blocking antibodies against B7-1 (CD80) and B7-2 (CD86) both found on the surface of antigen-presenting cells (e.g., Dendritic cells and macrophages).

Scientists have also targeted CD28 on the T cells by making anti-CD28 antibodies. Targeting both CD28 and the B7 molecules is trying to stop signal 2 of the transplant rejection sensitization phase. Without signal 2, there can be no rejection.

An important point to take home is that the latest efforts of immunosuppression are more targeted and so they don’t suppress the entire immune system but parts. Such a milestone is great because it can help your immune system to keep the graft and remain relatively competent to deal with the rest of the threats like pathogenic microorganisms.

Conclusion

Transplant rejection is an undesirable outcome of transplantation efforts. The rejection is usually by the immune system. It can be hyperacute, acute, or chronic rejection. Transplant rejection should be avoided by doing compatibility testing beforehand and contraindicating transplant procedures that are potentially dangerous.

There exist several types of drugs that can minimize the possibility and the intensity of transplant rejection if administered soon after transplantation. The drugs should be used with care to avoid compromising the immune system to a point of putting you at the risk of opportunistic infections.

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