– The MHC system affects autoimmune diseases by influencing the recognition and presentation of antigens to the immune system. Autoimmune diseases are diseases in which the immune system attacks the body's own tissues, causing inflammation and damage. Some examples of autoimmune diseases are:

• Type 1 diabetes.

• Rheumatoid arthritis.

• Multiple sclerosis, and

• Celiac disease.

– The MHC system consists of a group of genes that encode proteins on the cell surface that have an important role in immune response. The main role of the MHC system is to present antigenic peptides to T cells, which are a type of lymphocyte that can kill infected cells or activate other immune cells. The MHC system has two classes of molecules:

 - MHC  class I & MHC class II.

– MHC class I molecules present endogenous antigens, which are antigens that originate from within the cell, such as viral proteins, tumor antigens, or self-proteins that are altered by mutations or modifications. MHC class II molecules present exogenous antigens, which are antigens that originate from outside the cell, such as bacterial proteins, parasitic proteins, or allergens.

– The MHC genes are highly polymorphic, which means that they have many different variants in the population. This diversity allows the MHC system to bind and present a wide range of antigens to the immune system, enhancing the ability to recognize and eliminate foreign invaders. However, this diversity also poses a challenge for the maintenance of self-tolerance, which is the ability of the immune system to distinguish between self and non-self antigens, and to avoid attacking the body's own tissues. Certain MHC alleles are associated with an increased risk of autoimmune disease, as they may affect the recognition and presentation of self-antigens, the activation and regulation of immune cells, and the production and secretion of cytokines.

– Some of the mechanisms by which the MHC system may contribute to autoimmune disease are:

🔅Molecular Mimicry

– This is when a foreign antigen resembles a self-antigen, and the immune system cross-reacts with both, causing damage to the self-tissue. For example, some viral proteins may share epitopes with self-proteins, such as the myelin basic protein (MBP) in the central nervous system, which is a target of autoimmunity in multiple sclerosis. Certain MHC alleles may bind and present these mimetic antigens more efficiently, leading to a stronger immune response and a higher risk of autoimmunity.

🔅Altered Peptide Repertoire

– This is when a certain MHC allele binds and presents a different set of peptides than the normal allele, and some of these peptides may be self-antigens that are normally hidden or ignored by the immune system. For example, some MHC class II alleles may present peptides derived from the insulin molecule, which is a target of autoimmunity in type 1 diabetes. These peptides may activate autoreactive T cells that can attack the pancreatic beta cells that produce insulin.

🔅Aberrant Expression

– This is when the MHC molecules are expressed in abnormal amounts or locations, and expose self-antigens to the immune system that are normally sequestered or regulated. For example, some MHC class II molecules may be overexpressed or induced by viral infection or inflammation in tissues that are normally MHC class II negative, such as the thyroid gland, which is a target of autoimmunity in Graves' disease. These molecules may present self-antigens to the immune system, triggering an autoimmune response.

– These are some of the examples of how the MHC system affects autoimmune diseases, but there may be more that are not yet discovered or understood. The MHC system is involved in various immune functions, and its variants may influence the susceptibility or resistance to different autoimmune diseases, depending on the interaction with other genetic and environmental factors.

Can MHC genes be inherited?

– Yes, MHC genes can be inherited. MHC genes are a group of genes that code for proteins that are involved in the recognition and presentation of foreign antigens to the immune system. MHC genes are located on chromosome 6 and are divided into three classes:

• MHC class I.

• MHC class II.

• MHC class III.

– MHC genes are inherited in linked groups called haplotypes, which are sets of alleles that are inherited together from one parent. An individual inherits one haplotype from the mother and one haplotype from the father. In outbred populations, the offspring are generally heterozygous at many loci and will express both maternal and paternal MHC alleles. The alleles are co-dominantly expressed; that is, both maternal and paternal gene products are expressed in the same cells.

– The inheritance of MHC genes has important implications for organ transplantation, as the MHC molecules of the donor and the recipient may not match, leading to rejection of the transplanted tissue by the recipient's immune system. Therefore, one of the applications of the MHC system is to determine the compatibility of donor and recipient for organ transplantation, by testing their HLA types and finding the best match. This is also known as tissue typing or HLA typing.

– The inheritance of MHC genes also affects the susceptibility or resistance to certain diseases, especially autoimmune diseases, infectious diseases, and cancers. The MHC genes are highly polymorphic, which means that they have many different variants in the population. This diversity may influence the recognition and presentation of antigens, the activation and regulation of immune cells, and the production and secretion of cytokines.

– Therefore, by analyzing the MHC genes of patients and healthy controls, researchers can identify the MHC genes or alleles that are associated with increased or decreased risk of developing certain diseases, and understand the mechanisms and pathways involved in the pathogenesis and progression of these diseases.