Tumour Necrosis Factor Alpha Case Study

The bacteria produce a toxin known as cytolethal distending toxin. This toxin is believed to be the cause of disease in humans, but it isn't fully understood. It is also suspected to be a causative agent in Guillain-Barre syndrome, a disease that causes neuron demyelination, but again its role is not specifically understood.

Biomedical research disclosed the toxically active part of LPS is its lipid A. It produces a wide variety of pathophysiological effects such as fever, septic shock, leucopenia, leucocytosis, Shwartzman rectivity and even death (Caroff and Karibian., 2003). LPS do not act directly against cells or organs but through the immune system, specifically speaking, the monocytes and macrophages, thereby enhancing immune responses. Bacterial LPS if released into the mammalian blood can bind with specific types of binding proteins called as LPS binding proteins (LBP) which are normally present in the circulating blood (McCuskey et al., 1996). LBP is a glycoprotein which is 60kDa in size, produced in the hepatocytes and continuously secreted into the circulating blood. LBP posses binding sites for lipid A and recognize molecules, fragments or intact bacteria containing LPS (Schumann., 1992). Lipid A receptor system plays the critical role in the binding of LPS with LBP. Lipid A, a glucosamine disaccharide with hydroxy and substituted nonhydroxyl fattyacids acts as potent immunostimulators by recognizing LBP. The number of fattyacids attached to the lipid A is a strong determinant in deciding the strength of immune reactions evoked by LPS. Until 1990 there were no enough evidence to explain how lipidA getting intercalated into the lipid bilayer of host immune cells. It was believed that a non specific binding is occurring between lipid A and mammalian cell surface lipid bilayer. The

s symptoms, supported by x-rays and biopsies of the small and large intestine. Tumor necrosis factor alpha, TNFa, a protein released when the immune system is activated, is a major catalyst in the inflammatory process and is believed to play a major role in the pathogenesis of the disease.

This prevents the release of the inflammatory factors which cause Crohn’s disease; however it also prevents the intended effects of the cell, such as inducing cell apoptosis, and inhibiting viral replication. Due to these side effects, anti-TNF-α treatment can result in an increased risk of cancer, infection and fungal infections. Furthermore, although effective in most patients, 30% of people who receive this treatment do not respond and continue to show symptoms from Crohn’s [6]. This suggests that TNF-α is not the only cause of the disease, adding to the complexity of the

In the example of TNFa, excessive amounts can be highly cytotoxic and inappropriate expression of this cytokine has been linked to a variety of serious pathological problems such as septic shock (Baer et al., 1998) In view of the potential harm and effects, production of TNFa must be strictly regulated and controlled by negative feedback.

Tumor necrosis factor alpha is a multifunctional cytokine that plays an important role in apoptosis and cell survival with inflammation and immunity. The name TNF alpha was given due to its antitumor properties that have been used in a wide variety of diseases. TNF-alpha is used in cancer as a regional treatment for advanced soft tissue sarcomas (STS), isolated limb perfusion (ILP), irresectable tumor of several histological types, and melanoma in-transit metastases bound to a limb (http://theoncologist.alphamedpress.org/content/11/4/397.full).

Inflammation is a defense reaction, whereby harmful factors are removed and tissue structure and function are restored. During the acute phase of inflammation, first neutrophils will arrive, followed by monocytes. The monocytes mature into inflammatory macrophages and will finally affect the function of the resident tissue macrophages [Figure 1]. These responses lead to swelling, redness, heat and often pain. Once the first stimulus is removed, the reaction will stop and the inflammatory cells will be returned to pre-inflammatory numbers. Prostaglandins play an important role in immune reactions and are therefore often targeted by anti-inflammatory drugs, such as non-steroid anti-inflammatory drugs (NSAIDs). The specific role of prostaglandins and the mechanism of action of NSAIDs will be discussed (Ricciotti; FitzGerald, 2011).

Instead of being recognized and attacked by T cells, bacteria are recognized and attacked by complement proteins. “Complement proteins assist in bacterial killing via three pathways, the classical complement pathway, the alternative complement pathway or the lectin pathway. The first steps of the classical complement pathway require the binding of antibodies to the surface of the target bacterium” (Immune, 2016). At this point, the antibodies are handled by protein complexes which bind to the surface of the invader (much the same as the process of T cells in viruses). In other words, the body goes through a similar reaction of identifying and then attempting to destroy the invader, including the formation of a membrane attack complex. “MAC can insert into the cell membrane of Gram-negative, but not Gram-positive, bacteria. There, it produces pores that allow the entry of membrane damaging molecules, such as lysozyme, and makes the bacterium susceptible to osmotic lysis” (Immune,

The bacteria causing ulcers are called Helicobacter pylori. This bacteria is infectious to the stomach because it can adapt to the stomach's acidic environment. H. pylori have flagella which help the bacteria move into the mucous lining of the stomach by burrowing. The bacteria reach the neutral environment of epithelial cells and are safe from the high acidity environment of the stomach. Once H. pylori are the lining, the epithelial cells are exposed. Normally, ammonia neutralizes the stomach acid, protecting the mucous lining from being eroded. However, ammonia is lethal to epithelial cells and causes cellular death. This cell death results in an inflammatory response (Dixon, 2001). The inflammatory response includes cellular components of the body's immune system. Once H. pylori are in the epithelial cells, infection continues to spread as H. pylori insert its DNA into the cells. Some of the DNA is replicated with the epithelial cells' DNA while other mechanisms of the cells present the inserted bacterial DNA on the cells' surface. The cells become antigen presenting cells which signal white blood cells to the site of infection (Hunt, R.H., Camilleri, M., Crowe, S. E., El-Omar, E. M., Fox, J. G., Kuipers, E. J., . Tack, J., 2015). The response also signals G cells in the stomach to secrete gastrin, and gastrin stimulates parietal cells to produce more hydrochloric acid. The excessive production of the gastric hormones further damages the site of infection, and it can also damage the duodenum of the small intestine as the acids move through the stomach (Dixon,

Macrophages are large white blood cells found in the innate immune system that utilize phagocytosis to engulf pathogens in order to eliminate them, while osteoclasts are large cells found in the bone that break down and absorb bone tissue. Macrophages have properties that allow them to produce and secrete many chemokines and pro-inflammatory cytokines. These molecules can lead to increased angiogenesis in a microenvironment; additionally, the growth factors secreted by macrophages have the ability to promote tumor growth by promoting

RA begins with plasma cells overproducing rheumatic factors (RF) and antibodies to citrullinated protein antigen (ACPA). RF and ACPA can cause damage as well as activate macrophages, which play a large role in inflammation of the rheumatic synovium by drastically increasing the number of proinflammatory cytokines in the joint (Arend, 2001). Tumor necrosis factor alpha (TNF- α), interleukin-1 (IL-1) and interleukin-6 (IL-6) are the main cytokines involved in RA, which attract immune cells to the joints and cause tissue destruction (Arend, 2001). In addition, macrophages will also activate B and T cells via their MHC class II (Lee & Weinblatt, 2001). B and T cells are thought to play a role in the systemic aspects of RA but have an unclear function in synovial joints (Lee & Weinblatt, 2001).

The endotoxins are released into the immediate surroundings when bacteria undergo rapid proliferation with production of unused sections of bacterial cell wall or when the bacterial cell wall breaks.The toxic principal of the lipopolysaccharide molecule is generally similar regardless of the bacterial source (Burrows,1981). Metabolic toxins may accumulate as a result of incomplete elimination of toxic materials normally or abnormaly produced by the metabolism. In a healthy animal toxic products produced in the

Inflammation is the immune system’s response to infection and injury and has been implicated in the pathogeneses of arthritis, cancer and stroke, as well as in neurodegenerative and cardiovascular disease. It is an intrinsically beneficial event that leads to removal of offending factors and restoration of tissue structure and physiological function.

Rheumatoid arthritis (RA) is an autoimmune disease (McInnes & Schett, 2011; Smolen & Steiner, 2003; O'Dell, 2004) wherein the immune response of the body is aberrant, tagging the healthy cells of the body as non-self or foreign which therefore leads the body to attack and eliminate its own tissues. RA affects the synovial joints and is characterized by joint inflammation and the tissues surrounding it (Curtis, Gaffo, & Saag, 2006). Moreover, around millions of the Earth’s population are diagnosed with rheumatoid arthritis (Bingham & Ruffing, 2016). Patients detected to have this disease experience pain, stiffness or swelling in their joints (Centers for Disease Control and Prevention, nd; Drane, Berry, Bieri, McFarlane, & Brooks, 1997; Bellamy,

The mechanisms of endothelial cells and how it will contribute to the inflammation of some key diseases will be