The most important
Recognizes and destroys
Olga Skibina, "Scientific Russia"
MHC (English major histocompatibility complex) is the main histocompatibility complex. This is a large group of genes that occupies an important position in the immune system. MHC is responsible for the recognition of foreign objects in the body, the function of the immune response.
The main histocompatibility complex exists in all vertebrates and appeared 450 million years ago together with maxillofacial fish. Together with MHC, they developed immunoglobulins (antibodies) and T-cell receptors that recognize foreign substances.
The group of genes received the name "histocompatibility complex" during the study of foreign tissues. When organs and tissues do not match, rejection of the transplant is observed, which indicates the incompatibility of genes.
MNS was first described in the middle of the twentieth century. Georg Snell studied mice and found that they have a region of genes in the 17th chromosome that encode proteins and determine how compatible organs and tissues are during transplantation. If the donor and recipient have different MHCs, then the transplanted skin will not take root. Jean Dosse found the same genes in humans. He described the human leukocyte antigen (HLA), which is a complex of genes on the 6th chromosome of a person and is responsible for regulating the immune system. And Baruch Benaserraf, during experiments on guinea pigs, found out that the MHC genes determine the individual properties of the body and modulate the immune response. In 1980, these scientists received the Nobel Prize in Medicine and Physiology "for the discovery of genetically determined structures on the surface of cells that determine the immune response."
Rolf Zinkernagel and Docherty Peter also received the Nobel Prize in this field in 1996. They conducted studies that showed that the cells of the immune system, T-lymphocytes, determine the structure of the virus and compare the molecules of the body with the MHC. But the lymphocyte does not recognize a cell infected with a virus. After the scientists discovered that T-lymphocytes find a foreign object (antigen) by a small chain of organic molecules – a peptide, which is obtained by splitting a viral protein.
The main histocompatibility complex in all organisms differs in length, number of genes and location. In the human body, the most studied area of MHC is called Human Leukocyte Antigen (HLA). It consists of almost 4 million pairs of nucleotides, is located on the 6th chromosome and is considered the densest in the arrangement of genes, so it contains more than 200. It was discovered in the study of leukocytes in different people. This area is divided into 3 classes of genes. Classes I and II of MNS are the main participants of cellular immunity. When the protein molecules of the virus break down, they bind peptides and send them to the cell surface so that T-lymphocytes and other receptors recognize a foreign object and destroy infected cells. The immune system also destroys its own cells that are damaged or altered.
MHC proteins have polygenicity, i.e. there are several sets of MHC complex genes in the body. And polymorphism provides many variants for each gene. Some of them act as a signal for infection or the appearance of cancer cells in the early stages. And others manifest themselves in the placenta on the cells of the embryo, which contributes to immune tolerance during pregnancy. In this state, the body perceives the embryo not as a foreign object, but as its own, therefore it does not respond to it.
Fully human MNS was described in 1999 in the journal Nature thanks to the work of researchers from the UK, USA and Japan. At the same time, data on the chicken's MNS were published. The length of this region turned out to be 20 times smaller than in humans, and consists of only 19 genes of a different order. Among the functions it is responsible for egg production. Fish have even fewer genes. For example, the puffer fish has only 9 genes of first–class MHC molecules, and the aquarium fish danio has three.
Among the functions of the MNS there is not only participation in immunological processes. For example, in mice, MHC molecules regulate body weight. They can also be part of hormonal receptors.
In the 70s and 90s, a number of studies were conducted to find out the influence of the main histocompatibility complex on the choice of a sexual partner. It all started with mice and fish, and then experiments were conducted on humans. Studies have shown that women were more likely to choose partners whose MNS differed from the female one. But the results varied when hormonal oral contraceptives were used. Then the choice fell on a partner with a similar MNS.
During the formation of immunity, the child receives half of the genes from the father, and the other half from the mother. For the immune system, all proteins that are encoded by genes are considered foreign, so they can cause an immune response. During the first trimester, antibodies are produced in the body that protect the fetus from the maternal immune system, which, without these antibodies, perceives the embryo as tumor cells. And if the parents have 4 or more HLA class II antigens, then the number of antibodies decreases, which can provoke a miscarriage. Therefore, it is important that the spouses have different class II MNS.
MHC molecules are unique for each organism and allow you to distinguish your own objects from others. The study of MNS is very important for the development of clinical immunology. This knowledge is of great importance when searching for donors and recipients for organ transplantation. MNS data is used in determining the risks of pathologies, establishing the relationship between populations, as well as in the treatment of miscarriage.
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