Difference between revisions of "Team:Oxford/Description"
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| − | <p class="lead"> | + | <p class="lead">T helper cells (Th) are a component of the adaptive immune systems and are characterised by the presence of the CD4 protein on the cell surface. CD4+ cells are able to interact selectively with major histocompatibility complex 2 on the surface of antigen presenting cells such as macrophages and dendritic cells. These interactions facilitate the release of small proteins known as cytokines and so Th cells contribute to varying the activity of other cell types. More specifically, Th cells are required for the maturation of B cells to upregulate production of antibodies and the proliferation of cytotoxic T cells, which degrade cancerous or infected body cells. Our project focuses on detection of a particular subset of T helper cells namely, Th17 cells. Th17 cells produce interleukin- 17 (IL-17) and have a proinflammatory function, as well as regulating the production of neutrophils. Incorrect functioning of these cells is associated with the development of autoimmune diseases. Overactivation of Th17 populations that are responsive to self antigens causes the accumulation of antigen- antibody complexes, leading to type III hypersensitivity. This causes an inflammatory response and is associated with autoimmune diseases such as lupus and arthritis.</p> |
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| + | </p>Th17 cells are also closely associated with Treg cells as the chemicals required for Th17 differentiation and maturation are inhibitory with regard to this process for Treg cells. At low concentrations TGFβ associates with IL-6 and IL-21 to promotes Th17 differentiation; however, when TGFβ is at high concentrations, Treg differentiation is favoured as the production of IL-23 is repressed.</p> | ||
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| + | </p>In contrast to T helper cells, natural T regulatory cells (Tregs) are characterised by the presence of both the CD4 receptor and CD25. The role of Tregs is suppression of the action of helper and cytotoxic T cells, for example, by blocking the production of cytokines. They also suppress B cell and dendritic cell function, for example, via the production of inflammatory cytokines. The immunosuppressive role of Tregs is important in regulating the action of the Th cells and to prevent excessive inflammation and help to reduce self- reactivity, thereby limiting the development of autoimmune diseases. </p> | ||
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Revision as of 12:50, 13 October 2018
Description
Autoimmune Disease
Autoimmune diseases encompass a range of disorders that result from attack of self-tissues by a dysregulated immune system. More than 80 autoimmune diseases have been characterised, each with long-term effects on health, quality of life and cost to healthcare services. These include Crohn’s disease, Coeliac disease, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus and rheumatic disease.
Global Burden of IBD
Inflammatory Bowel Disease (IBD) is a heterogeneous group of autoimmune disorders encompassing Crohn’s disease and Ulcerative Colitis. It is estimated to affect 0.3% of the population in industrialised nations, including over 5 million adults in the UK, and 1.6 million in USA.
The global prevalence of IBD is increasing rapidly as countries become more developed. In addition, instances of IBD in developing countries are thought to be accelerated by the presence of bacteria, such as segmented filamentous bacteria (SFB), in water sources influencing the gut microbiome and host immune response. Gram positive SFB have recently been implicated in promoting the development of lymphocytes and the growth of Th17 populations. An additional effect of the signals required for Th17 differentiation is the inhibition of the production of Treg cells. Once fully differentiated, Th17 cells produce interleukin 17a (IL-17a) a proinflammatory cytokine. Elevated levels of IL-17a are associated with MS and the development of epilepsy and other autoimmune diseases. Most diagnoses occur between the ages of 20 and 30; the disease presents a significant burden to patients, societies, and healthcare systems. Current treatment is focused on symptom management, frequently resulting in sub-optimal control despite the burden of long-term treatment. Common therapeutics, such as corticosteroids, require regular administration, have many side-effects, and are less accessible in the developing world. The aim of our project is to address these problems and meet the notable, yet currently unmet, need for curative treatments for autoimmune diseases. This will be achieved via regulation of Treg and T helper cell populations to ensure immune responses of the correct magnitude. The specific control mechanism is discussed below.Immune Cell Populations
T helper cells (Th) are a component of the adaptive immune systems and are characterised by the presence of the CD4 protein on the cell surface. CD4+ cells are able to interact selectively with major histocompatibility complex 2 on the surface of antigen presenting cells such as macrophages and dendritic cells. These interactions facilitate the release of small proteins known as cytokines and so Th cells contribute to varying the activity of other cell types. More specifically, Th cells are required for the maturation of B cells to upregulate production of antibodies and the proliferation of cytotoxic T cells, which degrade cancerous or infected body cells. Our project focuses on detection of a particular subset of T helper cells namely, Th17 cells. Th17 cells produce interleukin- 17 (IL-17) and have a proinflammatory function, as well as regulating the production of neutrophils. Incorrect functioning of these cells is associated with the development of autoimmune diseases. Overactivation of Th17 populations that are responsive to self antigens causes the accumulation of antigen- antibody complexes, leading to type III hypersensitivity. This causes an inflammatory response and is associated with autoimmune diseases such as lupus and arthritis.
Th17 cells are also closely associated with Treg cells as the chemicals required for Th17 differentiation and maturation are inhibitory with regard to this process for Treg cells. At low concentrations TGFβ associates with IL-6 and IL-21 to promotes Th17 differentiation; however, when TGFβ is at high concentrations, Treg differentiation is favoured as the production of IL-23 is repressed. In contrast to T helper cells, natural T regulatory cells (Tregs) are characterised by the presence of both the CD4 receptor and CD25. The role of Tregs is suppression of the action of helper and cytotoxic T cells, for example, by blocking the production of cytokines. They also suppress B cell and dendritic cell function, for example, via the production of inflammatory cytokines. The immunosuppressive role of Tregs is important in regulating the action of the Th cells and to prevent excessive inflammation and help to reduce self- reactivity, thereby limiting the development of autoimmune diseases.