Major Histocompatibility Complex (MHC) Functions

Major Histocompatibility Complex (MHC) Functions The immune system is complex, containing thousands of components. On the whole this highly adaptive system works well, protecting the individual primarily against the threat of disease caused by infectious organisms (Wood, 2006). However, the immune system can deteriorate and fail should any component of this refined system be mutated or compromised. In this report, an overview of the immune system will be covered, along with an explanation of how the Major Histocompatibility Complex (MHC) functions specifically. An example of how the immune system can be compromised should the MHC molecule be short or absent will also be discussed with reference to a condition known as Bare Lymphocyte 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. Reference will be made to a case study related to the Bare Lymphocyte Syndrome and a conclusion will be made as to how this condition links to the MHC molecule specifically. An Overview of the Immune System The immune system can be split into two systems of immunity, innate and adaptive immunity. Innate immunity is the first line of defence against pathogens in the body, preventing most infections occurring by eliminating the pathogen within hours of being encountered. This is achieved by firstly possessing external barriers to infections such as skin, mucosa, gut flora and lysozymes in tears. Secondly, the immune system mounts an immediate attack against any infectious sources entering the host via pre-existing defence mechanisms within the body. Phagocytosis is the major element contributing to innate 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 using proteolytic enzymes (Wood, 2006). This process is aided by complement proteins and opsonisation. Another part of the innate immune response is for inflammation to occur . This enables cells and soluble factors from the bloodstream to be enlisted at a particular tissue site in order to assist in the fight against infection. These can be local or systemic and cause vasodilation to occur at the site of infection; cause the endothelium to have increased expression of adhesion molecules in the cells lining the blood vessels; cause increased vascular permeability and cause chemotactic factors to be produced, therefore 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 immune 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 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 employed 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 two types of T lymphocyte cells; those expressing CD4 molecules on their surface are referred to as Helper T cells or CD4 T cells, and those expressing CD8 molecules of their surface are referred to as cytotoxic T cells or CD8 T cells. The latter of these two T cells is important in the killing of virally infected cells (Kindt et. al., 2007). T cells recognise antigens by T cell Receptors (TcR) expressed 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, Class I and Class II MHC. Class I MHC molecules are glycoproteins expressed on the cell surface of most nucleated cells, whereas Class 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, macropha ges, dendritic cells and monocytes (Wood, 2006). Class I and II MHC molecules bind 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 cancer infected cells. (Sommer, 2005). Antigen Presentation of MHC Class I An 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 ÃŽ ± chain associated with a non-polymorphic ÃŽ ²2 microglobulin protein (Chaplin, 2010). In the antigen presentation pathway of MHC Class I, the viral protein is degraded into peptides through proteasome-mediated proteolysis which is then transported into the endoplasmic reticulum (ER) (fig 1). This transport process is facilitated by a transporter associated with antigen processing (TAP). Once in the ER, the translocated peptide binds to MHC Class I ÃŽ ± chains and ÃŽ ²2 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 Cl ass 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 Tatiana and Alexander Islayev; two siblings originally from Russia who were suffering from symptoms linked to Bare Lymphocyte Syndrome. Tatiana had severe bronchiectasis and a persistent 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 variety of respiratory viruses. Both Haemophilus influenza and Streptococcus pneumonia bacteria could be cultured 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, both children had elevated IgG 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 childrens DNA was analysed, it was found that they both had a mutation in the TAP-2 gene. Type I Bare Lymphocyte Syndrome Bare 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), modified 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 locus on chromosome 6. Deletion or mutation of either or both TA P-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 opportunistic 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 critical 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-complexed MHC Class I molecules are highly unstable and are therefore degraded quickly. This ultimately 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 activation 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 available; 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 tobacco and smoke should be avoided and also vaccinations should be performed against respiratory pathogens. Other than Bare lymphocyte syndrome, MHC class I allotype is also linked to various sero-negative spondarthropathies, such as Ankylosing spondylitis, Psoriatic Arthritis, Reiters Syndrome and Behcets syndrome.

Competitive advantages

Competitive Advantages Competitive advantage exist when an organization acquires or develops a combination of attributes that allows it to outstrip Its rivals. These properties can Include access to natural resources, such as Inexpensive power or high grade ores, or skilled personnel human resources and admission to highly developed. Competitive advantage can occur using new technologies such as robotics and information technology can provide, whether increase the percentage of the merchandise itself, as an advantage to the fashioning of the product, or as a competitive aid in the equines process.Tests is the market leader in the grocery retail market. Tests have reached this status by base on their competitive advantage to compete on grounds of pricing and distribution schemes. Tests also sustains and maintain its competitive advantage through product portfolio expansion and strategic competitive pricing to get and hold its status. The best reasons for the great competitive advantag e of Tests can be found from the way it reacted to the increase of the internet.The patient and dynamic approach enabled them to build and construct a sound long-term volts of hat the Internet meant for the core client of the company and to what kinds of actions that would take from the Tests. As a consequence of the early launch, when the expectations towards the Internet based commercial enterprises began to develop, Tests already been evolving the online help for a twosome of years. Tests is a purely online grocery retailer Scads 10 year Journey has been a noteworthy good story, as it has been able to exist in the very competitive online grocery market.It stays to be determined whether the Coda way with only warehouses becomes the sustainable or the good way to operate in the online grocery market. But, Tests and its competitions are well matched to make a motion to that model should the enough demand pick up. After that happens, they are well equipped by using the stores for bot h the rapidly growing click & collect and home delivery. Teaches foresight and clarity around the selected vision has rendered It almost 50% market share In a swiftly growing the market.Carefully emerging competitors or evaluate established In the crestless Industry to Identify their strong suits. Look at their weaknesses and opportunities creates for a new society to make a footing in the securities industry by addressing those gaps. It also evaluate companies that have create a leadership spot in other market places for lessons and ideas on how competitive advantages can effectively be built up. Review what is known about the competitive landscape to understand reason in the outside environment that may be a source by the competitive advantage.Then, the name of the competitive advantages for these companies have developed as well as the business strategies they have put into place for capitalize on them. With the continuous innovation and improvement companies are capable to suppl y customized products to Increase the number of clients. At the same time, clients are getting the benefit of the competitive marketplace environment, The exertion to provide best possible services to customers enables a company to make It In the rolled competition. At the same times, that company reaches an edge over its contenders and can glean the benefits (I. . The current business environment the companies with maximum number of customers and market share will have a competitive edge over others. For this company are striving to offer the best retailing services and ease the process of shopping. Competitive advantages that companies receive from online ordering services include: . Increased market share: more and more customers find it easy to buy online. A user friendly web site and app will attract more people. 2. Companies can get the â€Å"economies of scale† advantage.By this way companies are capable to provide discounted prices on products with attractive promotio n schemes. 3. Client Database: One of the best advantages that supermarkets can get from online ordering services is to maintain a customer database. This database keeps the track of customers' purchases, their picks and shopping trends. Companies using market intelligence can apply this data in several ways in order to provide best revises to their clients. Analysis Existing Competitor And Global Strategies Tests introduced the latest superstore concept in Britain.After a few years from the appearance superstore became very famous for its full range of products at competitive cost. After that, Tests introduced its first gas station, which had the lowest price for petrol but was adjacent to Tests superstore. Tests overtook from Ginsburg and became a I-J largest supermarket. Entering foreign markets in the beginning half of the ass were built primarily by buying existing stores or Joining the domestic retail leader. In year 1997 expansion in Asia market began from acquiring 13 shops from the CAP Group in Thailand and formed Tests Lotus.In 1999 market was reached by Joining with Samsung entrance to the South Korea. After that, loyalty card was introduced by Tests, branded ‘Club card', in year 1995. This card was given discount to customer but what is more important is this card gave an opportunity or chance to keep a hand on a pulse of customers need and to collect all data for future planning. New goals were set for expansion of the foreign market and developing of a non-food products. Every little helps† is the main advertising slogan appeared from Deco's.This advertisements in print and on television mainly include of product shots or an appropriate image against a white ground, and also include a price or appropriate text, for example â€Å"Tests Value†. On video, voiceless are provided by recognizable actors and sponsors, such as James Newsiest, Jane. Next, Deco's famous loyalty card. Club card still can be identified as the most successf ul strategy that makes for a huge role in financial profitability upkeep for Tests. Brand Tests can increase and hold its customer base because of its fixed tendency to attics client demands, customizing service to maintain lower prices.Masses tend to fill more of their needs in one topographic point and in shorter time, it indicates a requirement for large chains to extend their services into new markets as banking, Fairly traded products as tea, deep brown and cocoa are viable, and such merchandise is nowadays widely available on the majority of big chains. In 2005 Tests had the biggest range of fair-trade products in the I-J, it was represented by 91 fair-trade product line. However, distinguishing with the overall context of the 0,000 product lines it looks rather tiny (0. 2%) achievement by supporting third-world countries.In addition, there are prove that supermarkets exploiting customer goods will by overcharging for fair trade merchandise. â€Å"The supermarkets know that p eople do not work for the most inexpensive product when buying fair trade because they believe the surplus money is helping someone in the training world. † John McCabe. In international expansion Tests took to attention difference in preferences between different countries. It also very big attention was devoted to customers' needs usually t was implement in the product line. For example in the Czech Republic, Tests most focus on providing Czech products in retail stores.But in China, the locals opted to buy live fish, meat and other famous products such as instant noodles, unlike in European nations. Similarly in Thailand, the customers spent a vast balance of their salary or income for fresh foods. To adapt to the shopping habits of the Thai customers, Tests build a new market hall with is an area contiguous to the main store, where in 14 local vendors sold a range of meat, fresh fruits, veggies and other local food. This arena was planned to supply the Thai customers with traditional and local ambiance.On 1997, Tests announced the purchase of the retail branch of Associated British Foods, which consisted of the Crazy Prices chains in the Republic of Ireland and Northern Ireland, as well as associated businesses for IEEE Meg. This acquisition made it both a major presence in the bigger presence in Northern Ireland than Sunburst's and a Republic of Ireland. Deco's non-food marked faced a biggest competition level in KGB from such giants like Marks&Spenser and USDA. In the beginning of the entrance to the Hungarian market main competition was presented by little family-run stores, which served immediate needs to customers.The strategy against it was introduced more than 1000 its own label products at 20% cheaper price compare with branded ones. Deco's international expansion strategy in Asia was primarily represented as Joint ventures with the domestic partner firms like Charger Backhand in Thailand and Samsung Group in South Korea due to sensitivity of domestic market for foreigners and a bit more complicated than the rest of the others. In these mergers local personnel have an assured quantitative domination in low and middle management posts. It also formulates not big acquisitions an important part of its expansion strategy.In 2005, Tests announced that it was selling its operations in Taiwan in Careful and purchasing Carouser's stores in the Slovakia and Czech Republic. This both companies said that they were concentrate on their efforts in rural areas where they experienced good market positions. In 2007 Tests decided to run its online operations head office in Switzerland because of tax reasons. This can allows it to sell CDC, DVD's and electronic games through its website. This chance or opportunity was decide by the government in June 2008.Tests has done a devotion to corporate social obligation, by contributing about 1. 87% of its pre-tax earnings to schools scheme†, offer the computers in return for hospitals and schools getting vouchers from people who shopping at Tests. Until year 2004, Meme of equipment belonged to these establishments. The schema has been also implemented in Poland. â€Å"BIT – Tests Computers for Schools† started during the 2005/2006 association football season the company now sponsors the Tests Cup. The cup now runs a boy's competition at Under 13 year old and two girl's cups at Under 14 year old and Under 16 year old.Over 40,000 boys alone Joining the 2007/2008 competitions. Tests was accused by the I-J Office of Fair Trading (OFT) for being a part of a price cartel among the top five I-J supermarkets such as Safely, Morrison, Tests, USDA, and Kingsbury. The investigation started in 2007 and in the same year USDA, Kingsbury and Safely adjudged them mistake of working against consumer or customer interest by covering of 5000 farmers support in recovering after the foot-and-mouth disease. On the other hand, Tests were maintain after deny any activity in th is cartel.

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Arguments for Further Amendments to the NDPS Act - 2285 Words

ONE FINAL STEP FORWARD: ARGUMENTS FOR FURTHER AMENDMENTS TO THE NDPS ACT. ï ¿ ¼INTRODUCTION: ï ¿ ¼Ministry of Finance (MoF) backed by the Prime minister’s office(PMO) has decided to consider the option of further amending the Narcotic Drugs and Psychotropic Substances Act (NDPS) 1985 in the winter parliament session of 2015. The Ministry of Finance is expected to propose groundbreaking amendments which allow the state to introduce legal regulation of certain illicit drugs, including the decriminalization of marijuana possession. It is in this context that the Harm Reduction International – India Chapter (HRI-IC) has decided to commission this policy brief to provide recommendations that we believe should not be left out of the policy reform.†¦show more content†¦HRI-IC believes that the current drug policy in India has a deleterious effect on drug users and the youth of our nation – and therefore, feels duty bound to recommend the following policy changes in the NDPS Act: A. DELETION OF SECTION 27 FROM THE NDPS ACT: If incarceration reduced addiction, criminalization of addicts can be justified, but over the years drug addiction has only increased along with drug trafficking. (MOHFW, 2011) (Das, 2012). Stringent penalties provided for by the NDPS Act has done very little to deter drug use. In-fact, India houses the largest number of repeat offenders guilty of violating the NDPS Act. Around 63% of prisoners in India have a history of drug use and around 23% of the total number of prisoners has been apprehended for drug related offences (IHRN, 2009). In 2001 Portugal decriminalized possession, acquisition and consumption of narcotic substances for personal use. Ten years later irrefutable empirical evidence points to the fact that decriminalization did not lead to a spike in the number of drug dependent persons or an increase in drug related violence. On the contrary numerous studies show that there has been significant decline in petty crimes related to drug consumption like theft, because of availability of methadone treatment, decrease in HIV incidence amongst injecting drug users, along with reduction in recidivist crimes (Domoslawski, 2011)Show MoreRelatedIndia’s Drug Policy: Amend or Perish Essay examples2160 Words   |  9 Pagesof 25 years to impose this ban at the end of which the Narcotic Drugs and Psychotropic Substances Act, 1985 (NDPS) was enacted in conformity with the 1961 treaty. The Conundrum presented by Status Quo: †¢ Propagation of negative stereotypes: The most damaging aspect of the NDPS Act,1985 is that it rules out the possibility of an objective outlook on the multifaceted problem of drug abuse as the Act impetuously regards castigatory action as the only recourse (Letter to Ministry of Finance, 2012)