The major histocompatibility complex represents a complex of genes that produce immune proteins. These proteins are responsible for immune recognition and immunological individuality. They also play a major role in tissue compatibility in organ transplantation.
What is the major histocompatibility complex?
Major histocompatibility complexes are formed in all vertebrates. They are responsible for immune defense and recognition of the body’s own proteins. Thus, within the major histocompatibility complexes, antigens are presented on the surface of all cells. All nucleated cells contain receptors for the MHC class I protein complexes. The MHC class II protein complexes are in turn presented by the so-called antigen presenting cells such as macrophages, monocytes, dendritic cells in thymus, lymph nodes, spleen and blood or by B lymphocytes. The difference between the two major histocompatibility complexes is that intracellular antigens are presented in the MHC class I protein complex and extracellular antigens are presented in the MHC class II complex. There is also a third major histocompatibility complex called the MHC class III protein complex. This third complex involves plasma proteins that elicit a nonspecific immune response. All three complexes regulate the immune response while providing tolerance to endogenous proteins. The MHC class I protein complex identifies foreign proteins, such as those originating from viruses or degenerated cells. The infected or degenerated cell is destroyed by T-killer cells. In the case of the MHC class II protein complex, when extracellular foreign protein is present, T helper cells are activated, which ensure the formation of antibodies.
Anatomy and structure
Both major histocompatibility complexes consist of protein complexes that bind smaller peptides formed from the cleavage of endogenous or exogenous proteins. The MHC class I protein complex is a complex of one heavy and one smaller unit (β2-microglobulin) that have bound the antigen. For this purpose, the heavy chain contains three domains (α1 to α3), while the β2-microglobulin is the fourth domain. Domain α1 and α2 form a well in which the peptide is bound. In this process, the peptides are formed in large numbers by the enzyme proteasome from the continuously synthesized proteins. The cytotoxic T cells recognize whether they are degradation products of endogenous or exogenous proteins. If the proteins originate from viruses or degenerated cells, the killer T cells immediately begin to destroy the corresponding altered cell. Healthy cells are not attacked. The cytotoxic T cells are conditioned to do so. The MHC class II protein complex is also composed of two subunits, consisting of four domains in total. In contrast to the MHC class I protein complex, however, the subunits here are of equal size and are anchored in the cell membrane. Similar to the MHC class I protein complex, a peptide is anchored in a well between the domains. This is a peptide from an extracellular protein. T helper cells, like killer T cells, are selected for endogenous proteins. When peptides from foreign proteins are presented, the T-helper cells spring into action and ensure the formation of antibodies to bind the foreign proteins. Whereas the immune response in the MHC class I protein complex is cell-mediated, in the MHC class II protein complex it represents a hormonally controlled process.
Function and Tasks
The function of the major histocompatibility complexes is to recognize endogenous and exogenous proteins to ensure a targeted immune response. Each individual has his or her own specific proteins. Immune cells (T-killer cells, T-helper cells) are conditioned to these proteins. Immediate defense reactions are carried out against foreign proteins. This is necessary to protect the body from infection with bacteria, viruses or other pathogens. Through the presentation of antigens on the cell membrane, the immune system develops a tolerance to the body’s own proteins. Through a selection process, the immune cells learn to distinguish between diseased and healthy cells as well as between foreign and endogenous proteins. The presentation of antigens serves this selection process.If the antigens deviate from the usual pattern, the affected cells or the foreign proteins are destroyed. Via the MHC class I complex, the immune system is constantly on the lookout for degenerate protein or infection with viruses. Altered and abnormal cells are quickly eliminated. Via the MHC class II complex, the immune system immediately responds by producing antibodies when infection occurs or foreign protein enters the organism.
Diseases
At times, however, it happens that the immune system reacts against its own body. In this case, the tolerance of immune cells to the body’s own proteins is lost. The exact mechanism of this process is not yet fully understood. Usually, the immune system is directed against single antigens. This leads to limited reactions against individual organs. In principle, however, the immune cells can attack any organ. Thus, the diseases of the rheumatic circle have an autoimmunological basis. Here the immune system attacks the connective tissue and the joints. Permanent inflammatory reactions occur, which can destroy the joint system. Some severe intestinal diseases such as ulcerative colitis, among others, also represent autoimmune diseases. Another example of an autoimmune disease is the so-called Hashimoto’s thyroiditis. In this disease, the immune system is directed against the thyroid gland. Initially, an overactive thyroid gland develops and later an underactive thyroid gland. Furthermore, allergies also represent a malfunction of the immune system. Here the body reacts sensitively against normally harmless foreign proteins. As a rule, the immune system has learned to accept these proteins because they constantly affect the body. These include pollen, grasses, animal hair or various food proteins. However, antibodies against these proteins are formed via the MHC class II complex. When confronted with the allergens, respiratory symptoms, skin rashes, headaches, and a variety of other symptoms often occur immediately.
