Transplantation immunology and immunosuppression

The most important function of the immune system is to provide protection against infection. An essential part of this defence system consists in the mechanism which allows it to distinguish between 'friend and foe', i.e. between what belongs to the body and what is foreign to it. Transplants are frequently recognised as being, in the most literal sense of the term, foreign bodies, and as a result the recipient organism rejects them. The so-called human leukocyte antigen (HLA) system plays a decisive role in determining whether a transplant is accepted as belonging to the organism or regarded as being foreign to it. HLAs are to be found on practically all body cells. In preparing the transplantation of an organ or foreign tissue, donors are sought whose HLA systems are similar to the potential recipient's, i.e. who are HLA compatible. This minimises the severity of immunological defence reactions. Where the HLA parameters for the recipient and the donor are especially well matched, e.g. as is the case with identical twins, the reactions are mild or do not even occur at all, which means that the transplant is permanently accepted by the patient's organism. 

Today it is possible to perform organ transplants even when the HLA parameters are less compatible, because the reactions against the foreign organ can be controlled by means of immunosuppressive drugs. These are agents which suppress the immune system's natural defence mechanisms, at least to some extent. They are used not only for transplantations, but also to treat inflammation and autoimmune diseases. The development of immunosuppressive drugs began in the 1960s and it is continually being improved. There are many different substances which have immunosuppressive effects, the best known of which are Ciclosporin, Methotrexat, Azathioprin and calcineurin inhibitors. The recipient of a transplant is given a high dosage of immunosuppressive drugs immediately after the operation, which is then reduced over the following weeks and months. As immunosuppressive agents not only reduce the body's attempts to reject the new organ, but also suppress its defence against infections etc., the risk of the transplant recipient contracting an infection is very high. In addition, other disorders such as diabetes mellitus, high blood pressure or reduced kidney function can be triggered as well.

Stolp, J. / Zaitsu, M. / Wood, K. J. (2019): Immune Tolerance and Rejection in Organ Transplantation. In: Methods in Molecular Biology 1899, 159–180. doi: 10.1007/978-1-4939-8938-6_12. Online Version 

Kirste, G. (2008): Medizinische Aspekte der Organtransplantation. (Medical aspects of organ transplantation.) In: Beckmann, J. / Kirste, G. / Schreiber, H.-L. (ed.): Organtransplantation. Series “Ethics in the life sciences – DRZE expert reports”, vol. 7. Freiburg i.B.: Alber.

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