🔅 MHC

– The major histocompatibility complex (MHC) is a group of genes that code for proteins that are involved in the recognition and presentation of foreign antigens to the immune system. The MHC is also known as the human leukocyte antigen (HLA) system in humans, because the proteins encoded by the MHC genes are expressed on the surface of white blood cells (leukocytes) and other cells.

– The MHC is essential for the adaptive immune system, which is the branch of immunity that can generate specific and memory responses to pathogens and other foreign substances. The MHC genes are located on chromosome 6 and are divided into three classes: MHC class I, MHC class II, and MHC class III.

– MHC class I and II genes encode the cell surface molecules that present antigenic peptides to T cells, which are a type of lymphocyte that can kill infected cells or activate other immune cells. MHC class III genes encode other proteins that are involved in inflammation and complement activation, such as cytokines and complement components.

– MHC class I molecules are composed of a heavy chain (alpha chain) and a light chain (beta-2 microglobulin) that form a heterodimer. The heavy chain has three domains: alpha 1, alpha 2, and alpha 3. The alpha 1 and alpha 2 domains form a groove that binds the antigenic peptide, which is usually derived from the degradation of proteins inside the cell by proteasomes. The alpha 3 domain interacts with the CD8 molecule on cytotoxic T cells, which are the T cells that can kill infected or abnormal cells. MHC class I molecules are expressed on the surface of all nucleated cells, and they present endogenous antigens, which are antigens that originate from within the cell. Examples of endogenous antigens are: viral proteins, tumor antigens, or self-proteins that are altered by mutations or modifications.

– MHC class II molecules are composed of two chains (alpha chain and beta chain) that form a heterodimer. Both chains have two domains: alpha 1 and alpha 2, and beta 1 and beta 2. The alpha 1 and beta 1 domains form a groove that binds the antigenic peptide, which is usually derived from the uptake and processing of proteins outside the cell by endosomes and lysosomes. The alpha 2 and beta 2 domains interact with the CD4 molecule on helper T cells, which are the T cells that can secrete cytokines and stimulate other immune cells. MHC class II molecules are expressed on the surface of professional antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B cells, and they present exogenous antigens, which are antigens that originate from outside the cell. Examples of exogenous antigens are: bacterial proteins, parasitic proteins, or allergens.

– The MHC genes are highly polymorphic, which means that they have many different variants (alleles) in the population. This diversity allows the MHC molecules 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 organ transplantation, because 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.

– Another application of the MHC system is to study the associations of certain HLA types with various diseases, especially autoimmune diseases, infectious diseases, and cancers.

🔅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, celiac disease.

🔅Infectious diseases are diseases caused by pathogens, such as bacteria, viruses, fungi, or parasites. Some examples of infectious diseases are: tuberculosis, HIV/AIDS, malaria, and hepatitis.

🔅Cancers are diseases in which abnormal cells grow and spread uncontrollably, forming tumors or invading other organs. Some examples of cancers are: leukemia, lymphoma, breast cancer, and colon cancer.

– The HLA types of individuals may influence their susceptibility or resistance to these diseases, by affecting the recognition and presentation of antigens, the activation and regulation of immune cells, and the production and secretion of cytokines.

– Therefore, by analyzing the HLA types of patients and healthy controls, researchers can identify the HLA 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.

– The MHC system is also involved in other aspects of biology and medicine, such as mate selection, odor perception, vaccine development, and immunotherapy. Some studies have suggested that the MHC system may influence the choice of sexual partners, by affecting the preference for body odor or facial attractiveness.

– The hypothesis is that individuals may prefer mates with different or complementary MHC types, to increase the genetic diversity and immune fitness of their offspring. The MHC system may also affect the perception of body odor, by modulating the production and secretion of volatile organic compounds (VOCs) that contribute to the individual's scent.

– The MHC system may also play a role in the development of vaccines, by determining the immunogenicity and efficacy of different antigens and adjuvants.

– The MHC system may also be a target or a tool for immunotherapy, which is a type of therapy that uses the immune system to treat diseases, such as cancers or infections. For example, some immunotherapies may aim to enhance the expression or function of MHC molecules, to increase the presentation of tumor antigens or viral antigens, and stimulate the immune response. Alternatively, some immunotherapies may use synthetic or modified MHC molecules, to deliver specific antigens or modulate the activity of immune cells.