Major Histocompatibility Complex in Transplantation

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Table of Contents

Abstract
Introduction
Executive Discussion
Conclusion
References

Abstract

Transplantation

This is an immunological process of moving a section of a body part, tissue, or the whole organ from the donor to the recipient to save a life or enhance normal living and functioning of the body. Various types of transplantation exist such as Xenograft that involves the translation of tissue or organs between different animals that are not of the same species. The other kind of transplantation is the grafting of tissues and organs between members of the same species. In transplantation, one has to know the genetic makeup and similarity for effective grafting to occur, therefore isograft is carried out among the inbred species or identical twins.

Major histocompatibility complex

MHC is an immunological locus that controls the process of rejecting or accepting foreign particles, pathogens, or tissues in the body of the recipient. Major histocompatibility complex involves a complicated process of merging various tissues, organs, cells in the body for better functions of the body immune system. Therefore, MHC antigens can lead to a very strong and effective immune response and this is a vital procedure in determining the acceptance or the rejection of the grafted tissue, cells, or organs. This process is enhanced by two types of MHC i.e. MHC class1 and MHC class2 complex.

Introduction

In this world of science, some of the current undertakings involve organ transplantation. This process involves stern and great care in moving or transferring a section of an organ or a whole organ from the donor to the recipient. Sometimes a part of an organ may be transplanted from one side of the body to another on the same person; it is not a must that the transplantation may involve another person or donor.

The main purpose of transplantation is to save or replace the damaged part of the body or the organ that has failed to function properly. Mostly organ transplantation is a life-saving mechanism while tissue transplant can be done to enhance the normal existence of life or for aesthetic purposes. The major organs transplanted are sensitive organs that play a major role in human life and which cannot be substituted such as livers, hearts, kidneys, lungs even the skin, etc.

The process of organs transfusion cannot take place without proper understandings of how Major histocompatibility complex functions. This complex contains genes that immunologically control several antigens that determine the success of transplantation. These antigens can be divided into three major classes. This includes MHC class I, MHC class II, and MHC class III (Bochtler and Wahl, 2006). The MHC class I and MHC class II antigens are articulated on cells and tissues while the MHC class III antigens are represented on amino acids in serum and other body fluids such as C4, factor B, TNF. MHC class 1 and class 2 play major roles in transplantation.

Executive Discussion

Doctrines of Transplantation

The basic expectations of transplantation are that if the grafting is not done following the immunological know-how between the recipient and the donor, the graft won’t succeed. To avoid that failure, scientists have developed more competent transplantation by analyzing fully the major roles played by MHC class 1 and MHC class 2. This is because the immunocompetent recipient identifies and recognizes the foreign tissue or organ as antigens on the grafted body part. This provokes the immune system of the recipient to start and mount an immune response to fight the foreign tissue hence leading to a rejection www.jimmunol.org.

Therefore, mechanisms to confuse the immune system of the recipients to accept the foreign tissue as one of its own are some of the current undertakings to enhance successful transplantation. This is where the need to know the functions of MHC classes and how they are compatible with the immune system as a whole helps to solve the problem.

In this essence, immunologists have successfully studied the relationship between the MHC classes, immunoreactive T-cells, and different Immunoglobulins such as IgG, Ig M, Ig A, etc, and the whole lineage to the immune system. This is because if transplantation is done between the immunocompromised recipient and foreign lymphoid cells that are immunocompetent, the immunoreactive T-cells in the graft identifies and recognizes the foreign cells, therefore, treating them as antigens and in the process of immunological defense, the tissue is thoroughly damaged.

To avoid such failures immunologists have tried to study and have a better understanding as to how immunological mechanisms work, and by so doing, procedures to enhance graft survival have been initiated. Furthermore, scientists have tried to define and analyze fully how MHC antigens are bred or identified immunologically. Finally; immunologists have developed more effective and successful agents to immune systems such as immunosuppressive agents.

In the process of grafting and use of immunosuppressive agents the roles of MHC have been analyzed. MHC class II plays a major role in sensitive homeostatic proliferation and the increase of regulatory T cells. Liver transplantation can be carried out without the use of immunosuppressive agents. Therefore, the liver can be accepted spontaneously when it is transplanted between two species for example between B10 (KbAbEbDb) to C3H (KkAkEkDk) mouse. When it comes to the liver and heart, the two organs are rejected with time in C3H hosts after being desensitized with B10 skin grafts.

It is in the process of this study that other roles of MHC are realized. This involves MHC class 1 or class 2 that manifest its functions on the cell surfaces.

To ascertain the immunological investigation, further testing on mouse species to confirm the potential outcome was carried out. In the process, a skin graft from transgenic major histocompatibility complex class I (b2mmlUncbcr) gene of a knockout mouse was grafted onto an immature host two to three weeks before the whole organ was transplanted. Later it was discovered that when C3H recipients were allopresensitized with graft skin from class II deficient mice, the immune system mounted a fight against the foreign graft skin after some few days leading to its rejection (Epstein, RB, Bryant Thomas, ED, 2004 pg 209).

By comparing this to a liver graft, there is a contrast in that allopresensitization with skin from beta 2-m mutant; class I deficient mice did not considerably affect or influence the survival of either organ graft after which a. sensitization was conventional two weeks after skin grafting. This to some extent lasted for 11 weeks.

Measures to Enhance Graft Endurance

After knowing the effects of MHC classes and their relationship in the immunological context, it is of paramount importance to enhance graft survival by employing monitored procedures. This is one of the current procedures to enhance transplantation. In this context, immunologists have undertaken certain guidelines that can be relied upon when selecting donors and preparing the recipients before transplantation is done.

The most important guideline in donor selection is to identify the MHC classes between the host and the donor to know whether to apply immunosuppressive agents or a donor is an ideal person. Therefore, the MHC identity between the two must be known. In this case, grafts from human-leucocytes antigens between identical siblings are successful. Therefore, one should be able to match the human-leucocytes antigen D region. In this case, MHC function is essential (Lawrence B. and Susan, 1996).

Host preparation

Through advanced studies, the patient is thoroughly checked to confirm whether there are signs of hypersensitivity. In the process of transfusion, the recipient may get 2 to 5 transfusions of 110 to 200 ml blood from the donor between one to two weeks interval to observe any negative reactions in advance.

Immunosuppressant mechanisms

Immunologists have employed the use of Immunosuppressive therapy to the recipient. This is a vital procedure in allotransplantation. Some of the recent immunosuppressive agents are Atacrolimus, cyclosporine, and rapamycin. In immunological reactions, both FK506 and Cyclosporine A inhibit Interleukin-2 synthesis. This is again followed by Antigen-receptor binding. On the other hand, rapamycin distorts the signal transduction that follows Interleukin 2 – IL2 receptor interaction.

In the process, the three agents stop by blocking T cell proliferation as they try to immunological mount fight to the foreign tissues or organs. In some cases, chemicals are used to prevent the early rejection of a graft. This is achieved especially when immunologists employ the above-mentioned agents and do deep research on how they distort, interfere, or suppress the main functions of the cytokine profile. However, some natural killer cells (NK), interleukin hormones, and other related cytokines may trigger an inflammatory reaction around the grafted organ but this does not mean that the transfusion would not be successful. This is a mere indication of early but minor reactions as the recipient’s immune system gets prepared to accept and accommodate the newly replaced or grafted tissue, organ, etc.

The realized visible reaction is a result of MHC class functions and how this is manifested on the tissue or cell surfaces. However, if this would not be detected it means that the recipient’s immune system is not functioning properly. There might be a failure in the cytokine profile or the MHC classes do not match as expected. But this is a rare occurrence that is rectified. However, the cytokine profile that involves tumor necrosis factor-α is well manifested but is a good early indicator that immunologists have to be prepared to detect any malfunction that can lead to transfusion failure (Laurikka J.; Kuukasjarvi P.; Pehkonen E, 2006). This mostly occurs during blood transfusion whereby the serological typing and matching of the cells should be enhanced (Vriesendorp, Cache, Krumbacher, J., Albert, 1998- Page 209).

Conclusion

The overall mechanism and how the body’s immune system work is a complicated issue that needs to be analyzed critically. One has to understand the basic principles of the immunological reactions and the effects they can cause to the entire body system and the cytokines profile that results together with the antigen titer. The immunological reactions and the antigen titer can be used to determine the time of reaction. All these processes are related to MHC reactions and manifestation in the region of grafting. This is further reinforced by inflammatory reactions.

Due to understanding of the recipient versus graft-reaction, it is easier to detect the time of rejection because the time of reactions highly depends on how antigens of both the donor and the recipient differ. It is known that MHC antigens are the chief determinants in rejecting a graft. This is because there is immunological remembrance and secondary response in graft refusal. However, when the graft is rejected by a host, a second graft from the first donor, or another donor with similar histocompatibility antigens, would not be accepted in a much shorter time limit. This can highly save the consequences of failed graft.

References

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Cristina R. Angel M., Ochoa M.C., Amelia M., Alfredo M.J. Gonzalez M (2008). Role of MHC class 1 and polymorphisms in bodyweight regulation. Volume 3, pg 31-41.

Epstein, RB, Bryant Thomas, ED, (2004 pg 209) Marrow grafts and leukocyte infusions selected and transfused by histo-compatibility typing, Oxford University Press.

Immunology journal by Bochtler and Wahl (2006), functional and adaptive CD4 T Cells in MHC Class II, 177(12): 8307 – 8314.

Immune gene variability (MHC). Web.

Jardet TS, Gorg, Brown, JH LJ, Urban, RG, Strominger, JL, and Wiley, JC, Stern (1998, pg 118) Nature, the three major dimensions and structures of Human class II histo-compatibility antigen (HLA-DR1).

Kuukasjarvi P.; Laurikka J.; Pehkonen E. (2006). Web.

LB Schnook and SJ Lamont, (2004 pp 245-67) Major Histo-compatibility Complex sites in domestic animal Species, CRC Press.

Lawrence B. Schnook, Susan J. Lamont (1996) The Major Histo-compatibility Complex. Web.

Major histo-compatibility and organ transfusion. Web.

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Non-MHC transplantation antigens. Web.

Other roles of MHC classes. Web.

Susan J and Lawrence (1996) Major histo-compatibility complex, CRC Press.

Vriesendorp, Cache, Krumbacher. Albert, (1998- Page 209) serological typing and matching, CRC Press.

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