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13.6.4. Transplants and the phenomenon of rejections

Transplants and rejections

transplant consists of replacing a diseased organ with another that is working properly. An organ (or tissue and sometimes cells) is removed from a healthy individual (donor), and placed in the body of the same or another organism (recipient) in which it is not working properly. In the case of transplants of vital organs, the donor has to be in a state of “brain death”.

Transplants and their classes

Normally, the immune system of the recipient person recognizes the molecules of the graft and transplanted organ as foreign to the body and acts against them, producing a rejection against the transplanted organ.

Depending on the relationship between donor and recipient, transplants can be:

  • Autotransplantation, if the transplanted organ or tissue comes from the same individual.
  • Isotransplantation, if the donor is an individual genetically identical to the recipient. This occurs only between univitelline twins.
  • Allotransplantation, when the donor is a genetically different individual from the donor.
  • Xenotransplantation, if the donor and recipient belong to different species.

Naturally, the immune responses will be lower in autologous transplants, and higher in xenografts, since the donor and recipient tissues are less compatible. For this reason, autologous and isotransplants are safer than allogeneic or xenograft transplants, which have a higher risk of rejection.

The chances of rejection increase as the relationship between donor and recipient decreases. The xenotransplantation in humans, for example, derived from pork, the species which gives less problems, and there are even transgenic pigs expressing in its cells some human proteins.

Rejection classes

Although the medical techniques for transplantation are very advanced, the biggest problems are the availability of organs and the possibility of immune rejection by the recipient.

However, corneal transplantation does not usually cause rejection, since the cornea does not have lymphatic or blood circulation and, therefore, lymphocytes do not easily access it.

The rejection mechanism occurs as a response of the recipient's immune system to the donor tissue or organ with a certain surface antigen on the cells, which their T lymphocytes do not recognize as their own. This causes a large number of cytotoxic lymphocytes and macrophages to go to the transplanted organ , producing necrosis of the transplanted tissue or organ.

The cytotoxic lymphocytes activated the macrophages and also thanks to the interferon (interleukin) the NK cells that secrete perforins that attack cell membranes of transplantation and destroy them.

The neutrophils also phagocytose cells with opsonins and form platelet thrombi. The production of antibodies in response to MHC antigens activates the complement system that causes cell lysis .

Rejection is greater if the donor's surface antigens (MHC proteins) are different from those of the recipient. If the donor and recipient autoantigens do not match, rejection occurs, beginning with the attack of TC lymphocytes, causing lysis of cells in transplanted tissues. If the MHC autoantigens are identical, rejection does not occur, but this rarely occurs. For this reason, before transplanting an organ, it is necessary to test that the autoantigens of the donor and recipient cells are very similar.

In rejection, in addition to the action of TC lymphocytes, the specific humoral response (antibodies) and the nonspecific response (macrophagescomplement activation) also intervene .

Depending on the moment in which the rejection occurs, these types are distinguished:

  • The acute rejection occurs within 24 to 48 hours after transplantation, and is mainly due to the action of antibodies that bind to antigens of foreign cells causing their destruction.
  • The delayed or chronic rejection several weeks or months after transplantation appears. It is caused by the development of memory T lymphocytes which, in the presence of antigens from the transplanted organ, activate TC lymphocytes  and macrophages  that go to the affected area and act against the transplanted organ.

The rejection depends on the genetic relationship between donor and recipient, and occurs because the proteins of the major histocompatibility complex (HLAin the human species) that lymphocytes have in their membrane and the vast majority of cells that each person has, are recognized by their immune system. MHC proteins in transplanted tissue cells act as foreign antigens and cause rejection.

If the donor and recipient have the same histocompatibility systems, there is no problem of rejection, but only univitelline twins are genetically the same. In cases of autologous transplants, such as skin, for example, there is no rejection. There is also no problem of rejection in tissue transplants that do not have blood supply or it is very scarce, as in the case of corneal transplantation, since it does not produce any immune reaction.

In the rest of the transplants, to minimize rejection, it is a question of having the maximum degree of histocompatibility between donor and recipient, looking for the most compatible according to their blood group and the HLA type of their cells. The recipient has to undergo immunosuppressant treatments to decrease the activity of the immune system and not recognize the transplanted tissue as foreign, which can cause them to have some infection problems due to their weakened immune system.

Questions that have come out in University entrance exams (Selectividad, EBAU, EvAU)

Aragon. September 2018, option A, question 5

If an organ is transplanted from one person to another, the transplanted person must undergo immunosuppression treatment. However, one person who was burned on one arm had skin transplanted from his back to the burned area and the doctors did not prescribe any immunosuppression treatment. Explain why immunosuppressants are prescribed in one case and not in another. (1 point)

Aragon. September 2017, option A, question 4.

Define each of these terms and express the differences between them. (1 point)

b) Transplantation and rejection. (0.5 points)

Aragon. June 2017, option A, question 5 .

Define the following concepts related to the immune system: transplant rejection. (0.2 points)

Aragon. September 2015, option B, question 5 .

Define the following statements: (2 points)

Rejection of a transplant. (0.5 points)

Aragon. June 2014, option B, question 4 .

Questions: (2 points)

a) Why is there no rejection in a transplant between univitelline twins? (1 point)

Aragon. September 2001, option B. Issue 2 . (2 points)

a) What is the immunological reason for the rejection that occurs in transplants? Can there be rejection between siblings? Why?.

b) What are the functions of B lymphocytes? What about T lymphocytes?

Canarias, June 2017, option a, question 10.

Our country revalidates world leadership for another year and closes the 25th anniversary of the National Transplant Organization (ONT) with an all-time high in the number of donors. (Source: www.msssi.es)

a. What is the cause of the rejection by the recipient organism?

b. Before the operation, the recipient undergoes immunosuppressive treatment. What is the goal of this  treatment?

Basque Country, July 2018, option B, question 5.

According to news published in the press, Spain maintains the world leadership in organ transplants.

Regarding organ transplants:

a) Why is it that an organism rejects a healthy organ that is transplanted from another individual? How are rejections treated in clinical practice? Reason for your answers. (1 point)

b) In the case of univiteline twins, what type of donor would each be for the other brother? And the brothers who are not univitelinos ?. Justify your answers. (1 point)

Basque Country, July 2020, extraordinary test, option 3B

Organ transplants are necessary surgical procedures when there are irreversible problems with the patient's natural organ.

a) (0.5 points) What is the biggest problem that can appear after a transplant?

b) (0.5 points) What molecules are the triggers of this problem, and which are the cells that act first?

c) (0.5 points) What types of drugs are used to prevent it?

d) (1 point) Indicate the types of transplantation that you know according to the origin of the transplanted organ.

Aragon, July 2021, question 9

9. When performing a transplant between univiteline twins, Ángel and Vicente, it was observed that rejection did not occur: (2 points)

a) Explain what is the rejection of an organ and why in this case it does not occur. (0.6 p)

On the other hand, when inoculating the same antigen simultaneously to these two univitelline twins, it was observed that Ángel produced in 5 days an amount of antibodies that Vicente took about 20 days to produce.
b) Define antigen , antibody , autoimmunity and immunodeficiency . (0.8 p)
c) Propose a simple hypothesis that explains this unequal behavior of the twins. Reason for it. (0.3 p)
d) According to this hypothesis, would the same occur with any antigen administered? (0.3 p)

Canary Islands, July 2021, question 19

19. Spain is among the countries with the highest rate of organ transplants per inhabitant. Regardless of the transplanted organ, the technique depends on the immune system of the person receiving the organ.

a. Why can't an organ be transplanted from one person to another if both the donor and the recipient belong to the same species?
b. What should a transplant recipient do to minimize the chances of rejection?
c. Why does a univiteline twin transplant not lead to rejection?