Major Histocompatibility Complex (MHC) Functions

study Histocompatibility Complex (MHC) FunctionsThe resistive dodging is complex, containing thousands of comp peerlessnts. On the whole this highly adaptative system works well, protecting the individual primarily against the threat of affection suitd by infectious organisms (Wood, 2006). However, the tolerant system can deteriorate and plump should any component of this refined system be mutated or compromised.In this report, an overview of the immune system ordain be covered, along with an explanation of how the major(ip) Histocompatibility Complex (MHC) functions special(prenominal)ally. An example of how the immune system can be compromised should the MHC shred be short or absent will also be discussed with reference to a condition known as B ar lymph mobile phone Syndrome. How the MHC molecule contributes to a healthy immune system will be discussed, along with the effect an MHC deficiency has and how this compromises the immune system at a molecular level. Referen ce will be made to a result study related to the B be lymph cell Syndrome and a conclusion will be made as to how this condition links to the MHC molecule specifically.An Overview of the repellent SystemThe immune system can be split into ii systems of immunity, inborn and adaptive immunity. Innate immunity is the first line of defensive structure against pathogens in the body, preventing most infections occurring by eliminating the pathogen within hours of macrocosm encountered. This is achieved by for the first time possessing external barriers to infections much(prenominal) as skin, mucosa, gut flora and lysozymes in tears. Secondly, the immune system mounts an immediate attack against any infectious sources entering the server via pre-existing defence mechanisms within the body. Phagocytosis is the major element contributing to ignorant immunity. This is the ingestion and destruction of microbes by phagocytes in a process by which the phagocyte attaches to the microbe in question, engulfs the microbe, kills the microbe and then degrades the microbe apply proteolytic enzymes (Wood, 2006). This process is aided by complement proteins and opsonisation. A nonher post of the innate immune response is for inflammation to occur. This enables cells and soluble factors from the sourcestream to be enlisted at a particular tissue site in collection to assist in the fight against infection. These can be local or systemic and deliver vasodilation to occur at the site of infection cause the endothelium to bring in increased expression of adhesion molecules in the cells lining the blood vessels cause increased vascular permeability and cause chemotactic factors to be produced, thence attracting cells into the tissue from the bloodstream (Wood, 2006). Overall, innate immunity is the first step in combating infection in the body however a more specific system is often required.Acquired immunity occurs when a pathogen enters the body which the innate immun e system cannot destroy, whether it is the pathogen has evolved a way of being avoided by the cells in the innate immune system or whether it be the pathogen expresses molecules similar to host cells as in the case of viruses. In such(prenominal) cases as these, acquired immunity is needed, where lymphocytes are used to identify, engulf and kill the pathogen in question. This is a more evolutionary advanced system compared to innate immunity. Two types of lymphocyte cells are assiduous in the acquired immune response these are B lymphocyte cells, which are responsible for creating antibodies and T lymphocyte cells, which are more complex in their receptor and require cell-to-cell contact. There are devil types of T lymphocyte cells those expressing CD4 molecules on their bug out are referred to as Helper T cells or CD4 T cells, and those expressing CD8 molecules of their start are referred to as cytotoxic T cells or CD8 T cells. The latter of these two T cells is primal in the cleanup of virally infected cells (Kindt et. al., 2007). T cells cognise antigens by T cell Receptors (TcR) uttered on their surface each T cell expresses only one TcR specifically. T cells do not recognise free antigens but recognise antigens associated with molecules on the surface of cells called Major Histocompatibility Complex (MHC) molecules (Wood, 2006). MHC molecules specifically for the human species are known as Human Leukocyte Antigens (HLA) these are located on chromosome 6 (Kindt et, al., 2007). The MHC constitutes important genetic components of the mammalian immune system. There are two types of MHC molecules, secernate I and layer II MHC. program I MHC molecules are glycoproteins expressed on the cell surface of most nucleated cells, whereas affiliate II MHC molecules are also glycoproteins but are restricted in their expression, primarily being found on cells of the immune system such as B cells, macrophages, dendritic cells and monocytes (Wood, 2006). Class I and II MHC molecules adjudge to antigens derived from pathogens and present them to T lymphocytes (Sommer, 2005). CD8 T cells recognise antigens presented by Class I MHC molecules whereas CD4 T cells recognise antigens presented by Class II MHC molecules. MHC molecules play an important role in immune defence against intracellular pathogens, peptides derived from viral proteins and crab louse infected cells. (Sommer, 2005).Antigen Presentation of MHC Class IAn event involving generation of peptides from proteins in the cell and displaying these peptides on the plasma membrane is called antigen processing and presentation (Benjamini et al., 1996). MHC Class I molecules consists of HLA-A, HLA-B and HLA-C. HLA are cell surface heterodimers consisting of a polymorphic cooking stove associated with a non-polymorphic 2 microglobulin protein (Chaplin, 2010). In the antigen presentation pathway of MHC Class I, the viral protein is degraded into peptides through proteasome-mediated pr oteolysis which is then transported into the endoplasmic reticulum (ER) (fig 1). This transport process is facilitated by a transporter associated with antigen processing ( smasher). Once in the ER, the translocated peptide binds to MHC Class I chains and 2 microglobulin through momentary interaction of MHC Class I heterodimers and TAP (Chaplin, 2010). This momentary interaction is carried out with the help of Tapasin (fig 2). This binding of peptide and MHC Class I results in structural changes eventually leading to the dissociation of peptide-MHC Class I complex (Chaplin, 2010). This peptide-MHC Class I complex then migrates to the cell surface where it is recognised by CD8 T cells triggering the associated immune response. (Raghavan,1999).When the immune system is working correctly, pathogens entering the body will be destroyed rapidly. However, if a component of the immune system is compromised, devastating effects can be seen. An example of this was seen in the case study of T atiana and horse parsley Islayev two siblings in the first place from Russia who were suffering from symptoms linked to denude Lymphocyte Syndrome. Tatiana had severe bronchiectasis and a permanent cough which produced yellow-green sputum. She had been chronically ill since the age of 4 when she had begun to have repeated infections of the sinuses, middle ear and lungs, all due to a transition of respiratory viruses. Both Haemophilus influenza and Streptococcus pneumonia bacteria could be well-mannered from her sputum. She had been prescribed frequent antibiotic treatments to control her fevers and cough with no success. Her brother, Alexander was also showing the same symptoms. When their blood was examined, some(prenominal) children had elevated immunoglobulin G levels with over 90% of their T cells being CD4 and only 10% being CD8. Both children expressed very small amounts of MHC Class I molecules in their cells but expressed MHC Class II molecules normally. When the child rens DNA was analysed, it was found that they two had a innovation in the TAP-2 gene.Type I Bare Lymphocyte SyndromeBare Lymphocyte Syndrome (BLS) Type I also known as MHC Class I deficiency, is characterized by a severe down-regulation of MHC class I and/or class II molecules (Gadola et. al., 2000). Type 1 BLS is due to a defect confined to MHC class I molecules, while type 2 BLS shows down-regulation of MHC class II molecules. Like any other cell surface protein MHC class I molecules are synthesised in the rough endoplasmic reticulum (RER), change in the Golgi apparatus and are transported in transport vesicles to the cell surface (Wood, 2006). MHC class I molecules bind to different sets of peptides. Translocation of peptides derived from degradation of cytosolic proteins from the cytoplasm into the RER is negotiated by transporter molecules known as transporter associated with antigen processing (TAP) molecules. TAP is a heterodimer consisting of two subunits, TAP-1 and TAP-2 , which are encoded in the class II region of the MHC locale on chromosome 6. Deletion or mutation of either or both TAP-1 and TAP-2 proteins severely impairs the translocation of peptides into the RER, the result of which is reduced surface expression of MHC class I molecules (Gadola et. al., 2000). BLS is manifested as a combined immunodeficiency presenting early in life. BLS manifests during the first 6 years of life where affected individuals are susceptible to recurrent opportunist bacterial infections especially of the upper respiratory tract. In BLS, the underlying cause of Class I deficiency is due to a nonsense mutation in the TAP (Clement et. al., 1988).As discussed earlier, TAP is involved in the precise step of transporting peptides to the inner lumen of ER. In BLS, the deficiencies of active TAP results in the impairment of the transport of peptide to ER. This inefficient transport means that few or no MHC Class I molecules can be complexed with peptides. The un-compl exed MHC Class I molecules are highly unstable and are therefore degraded quickly. This lastly results in low levels of peptide-MHC Class I complex being expressed on the plasma membrane. In this way, deficiency in active TAP leads to low antigen presentation via MHC Class I molecules resulting in inefficient energizing of CD8 T lymphocytes and consequently a compromised immune response.The basis of bare lymphocyte syndrome can be concluded from protein coded genes that are transformed and are not able to control the expression of the MHC I genes. Till today a beneficial treatment of TAP deficiency is not yet lendable gene therapy isnt possible as almost all of the HLA class I molecule express on nucleated cells. If there is damage to the bronchial and pulmonary tissue lung transplantation can be performed. Contact with baccy and smoke should be avoided and also vaccinations should be performed against respiratory pathogens. Other than Bare lymphocyte syndrome, MHC class I allotyp e is also linked to various sero-negative spondarthropathies, such as Ankylosing spondylitis, Psoriatic Arthritis, Reiters Syndrome and Behcets syndrome.