Autoimmune disorder Major histocompatibility complex : Major histocompatibility complex, also called the human leucocyte antigen (HLA) complex is a 4 megahase region on chromosome 6. This region is densely packed with genes. These genes encodes two major proteins or antigens i.e., MHC I & MHC II. These proteins play an impoant role in the differentiation of foreign cells from host cell. Presence of these proteins is necessary for identification of host cells. Identification of the cells is impoant for immune responses. If the cell is recognised as self, the immune system will not mount an immune response against it. How does MHC helps in this ??? Cells continuously display small pieces of their own internal protein, carrying them, outsie the cell membrane where the immune system can see them. These peptides are just pieces of the normal proteins found inside the cell. These peptides are held together at the cell surface by major histocompatibility complex, which holds these peptides together for the immune system to examine them. Each persons immune system is customized early in life to ignore these peptides, so healthy cells are not able to trigger the immune system and they are left alone. But if any virus or other microorganism is multiplying inside the cell, the peptides synthesized by it also is displayed on the surface. The MHC displays these unusual (foreign) protein on the surface of the cell. The immune system is triggered because of these peptides, staing, a series of event that will eventually lead to killing of the cell containing foreign peptide. MHC is also the cause of tissue rejection during skin grafts and organ grafts. This is how the MHC protein got its name; the term histocompatibility refers to the difficulty of finding compatible grafts between a donor and a patient. Each person has their own collection of MHC molecules. If you graft a piece of skin that has a different collection of MHC types they will trigger the immune system to destroy the cell. So a compatible donor is needed such as a relative who has a similar collection of MHC molecules. MHC is also active against cancer Cancer cells, like normal cells, display pieces of their own protein on their surface. So if any of these proteins carries recognizable cancer mutations, this provides a signal to the immune system that something is wrong and the cell is killed. MHC plays role in activation of T helper cells (Th) MHC class II molecules are present on the membranes of dendritic cells, macrophages. These cell function as antigen presenting cell during immune response. They capture the antigen and present it to T helper cells. In response, the T helper cells secrete cytokines that stimulate B cell proliferation and antibody production. The impoant point about T helper cells is that they respond to only those antigens which have been presented to them by cells that have host matching MHC complex on the presenting cell. In general the antigen presenting cell .first phagocytoses the protein antigen and cleaves it to peptides in the lysosomes. These peptides are then extruded and attached to the presenting cell's surface MHC complex. T helper cells first, make sure, that these MHC class II molecules are host's own MHC and then responds appropriately. So, we can say that receptor on the T helper cell is thus responsive to the combination of antigen and host matching MHC complex on the presenting cell. Helper / inducer T cells (CD4)---) MHC class II restriction - Suppressor T cells (CD8) MHC class I restriction Cytolytic cytotoxic T cells (CD8) MHC class I restriction (Kills viral infected cells, tumor cells, facilitates graft rejection)