Multiple Sclerosis (MS) is a chronic and non-traumatic neurological disease. In 1968 Jean-martin Charcot first discovered MS. The cause behind the disorder of MS is still unidentified, though it is supposed to be genetic and environmental. T cell is also considered to be one of the reasons of MS.
Jean-Martin Charcot first discovered Multiple sclerosis in 1968 (Viglietta et al 2004). It is a most common non-traumatic neurological illness. 20 to 40 years people are most commonly affected, more women are affected then men (Tripoliti et al 2007). More then 75% people affected by MS are unemployed within 10 years (Tripoliti et al 2007). 1 in 600 people are diagnosed with multiple sclerosis that is nearly 100 thousand people in the world (Viglietta et al 2004). 15% of the deaths related to MS are due to depressive disorders rather than other neurological conditions and suicide accounts (Tripoliti et al 2007).
3. Symptom and reason:
Pain is a well known symptom of MS. 75% of patients with multiple sclerosis suffers with Naturopathic pain (NPP), placing it as the second worst disease-induced symptom. Sensory symptom of MS includes pains such as pins and needles, burning, shooting and stabling pain with or without troubling and numbness. The immune system mediated induction of pain and the known role that inflammatory cytokines such as TNF-α have been in the development of MS (Zozulya and Wiendl 2008).
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MS are developed by genetic and environmental factor (Zozulya et al 2008). 20 to 40% have increased chance of MS due to their siblings are already diagnosed with MS. The genetic effects of MS are major histocompatability complex (MHC), T-cell receptor (TCR), immunoglobulin heavy chain(IgH) and myelin basic protein(MBP) (Steinman, 2001).
The nerves are also affected by MS. Nerves are made of fibre looking like a tiny wires. Nerve fibres transmit electrical signals to the rest of the body from spinal cord, brain and vice versa. Myelin is a sheath which protects the nerve. It is also the white matter in brain. Myelin helps carry messengers along the nerves. The myelin sheath inflames the nerve when MS attacks. This inflammation may not create any permanent damage. But myelin sheath inflammation might continue damaging it at the point of attack. Continuous inflammation causes tissue damage on the damaged myelin sheath known as sclerosis or plaques, this is called demyelination and the damaged parts of the central nervous system are called multiple sclerosis. Demyelinations are fully understood. It is an autoimmune disease. It is initiated by T4 lymphocytes (protein molecule in blood of the MHC class II redistricted CD4+) (Lassmann et al 2004).
Two stages of multiple sclerosis are the attack of the auto-immune and neurolegeneration. In multiple sclerosis important elements are the auto reactive responses of the immune self-tolerance and deregulation of the inflammatory responses. The immune system has equilibrium system that maintains a balance between triggering of inflammatory responses and self directed autoimmunity.
4. T regular cell
T-cell are called so because T cell is processed in the thymus. T-cells travel throughout the body looking for foreign objects to attack, identifying and responding to each specific antigen. Auto reactive T cells presents in the normal body controlled autoimmune diseases (Viglietta et al 2004).
Researches have been experimenting on mice to understand the activities of T cell. Natural autoimmune diseases occurred in mice when the T cells were targeted and deleted. The development of variants of EAE (experimental autoimmune encephalomycilis) can be prevented with the enlargement of T regular cell function (Zozulya and Wiendl 2008). Immune system is usually in balance and dysfunctions in autoimmune disease. The immune system maintains a stability between activated inflammatory responses, activation of population of effectors cells and TH1 and TH2 maintain by regulatory cell. In MS, machineries do not work (Kasper et al 2007).
An active immune system is indicated by the transfer of the cells ability to transfer disease resistance or the ability to transfer disease resistance or autoimmune cells are induced by antigen or the ability of the immune cell to unmark impulse. In MS, contributes to the detachment between development of disease and the presence of auto-reactive T cells. The cytokine secretion profile and surface phenotype classifies the T regular cell. T cells Inflammation is regulated by two populations:
Always on Time
Marked to Standard
nTREG(natural T cells)and
iTREG (Inducible T regular cell)
4. a. Natural T cell
Natural T cells are produced in the Thymus. T cells are inhabitants residing in CD4 lymphocytes are expressed as the repression factor FOXP3 and nterleukin -2 receptor CD-25. In human immune system this cells are of 5 to 20% of the entire CD4+ cell population. T-cells are identify of main histo-compatibility to antigens and/ or high concentration of Interleukin -2 released by TH 1 cell are activated (Zozulya and wiendl 2008). TH1 cells releases high concentration of interleukin 2 or exposure to antigens. TH1 cells could activate natural T cells which are normally devoid of antigenic sensitivity (Kasper et al 2007).
T regular cells are of three subpopulation on the basis of the surface markers,
CD8+ T regular cell
TR 1 cell (Kasper et al 2007).
T regular cells have two common subsets T helper 3 and T helper 1. Though there are differentiation between these different inducible, T regular subsets are becoming more unclear (Zozulya and wiendl 2008).
4. b. Naturally CD4+ CD25+ regulatory T cell
Sakaguchi and colleagues first defined in 1995. In human and mice cell contain five to ten percent of the peripheral CD4+ T cells. Performance the CD4+CD25+ subset into thymes nude mice they showed they allowed inactive transfer of T cells resulted natural increase of various T cell mediated autoimmune diseases. Varity of immune systems are presence of these cells (Lan et al 2005).
5. Phenotype of natural T regular cells
Natural T cells are similar to memory. T cell receptor collection is different than conventional T cell population. Natural T regular cells are anergic in vitro in the present form of conventional T cell stimuli, plate or bead-bound anti-CD3, CD46 and IL- 2 an increase in granularity and express granzyme A, while relating a packed in nuclear chromatin (Lan et al 2005).
T cells mechanisms are still unclear. The cruel target if natural T cells include cells is adaptive innate immune system. T cells are able of suppressing the propagation and cytokine production of predictable CD4+ and CD8+ lymphocytes
(Lan et al 2005).
6. Inducible T regular cell
T- helper cells or TH3 are included in the inducible T regular cell. The inducible T cells come from native T cells. Native cells can be type 1 T regular cells or CD4+ or CD8+. T regular cells may or may not express FOXP3 and also induced in the border from CD4+ cell. Certain CD8+ 1 T regular cells that have lack expression of CD28 in immune responses by straight interacting with antign presenting and rending tolergenic (Zozulya and wiendl 2008).
7. Interleukin-10 producing Tr1 inducible T regular (iT regular)
Interleukin-10 is production from Tr1 inducible T regular cell. Tr1 is specific for antigens including self antigens. Interleukin-10 producing Tr1 cells can be induced in vitro by differentiation of resting or naïve CD4+T cells in the presence of interleukin-10, immature dendritic cells, activation with anti-CD3 and anti-CD46.Tr1 inducible T regular are similar to natural T regular in that they are both anergic in vitro and express CTLA-4, in contrast to natural T regular Tr1 inducible (Zozulya and wiendl 2008).
8. T cells and autoimmune diseases
T cell plays important role in autoimmune diseases. Mice body is used to understand how the T cell works in autoimmune diseases. Self-antigen reactive is a key factor of T cell. T cells are derived from lymphoid in the born marrow. In normal immune system B and T cells attends the same antigen, but recognizes different things. T cells are active B cells in normal immune system and can produced large quantities of antibodies. T cells can bypass some rare item, like super-antigen. Super-antigens install B cell's polyclonal activation or T cells straight binding to the β-subunit of T cell receptors (Zozulya and wiendl 2008). .
Autoimmune disorder is the failure to recognize its own body part and allows an immune response its own cells and tissue. It is a phenomenon of immunological tolerance to self antigens (Lan et al 2005). Regular T cells are control self-antigen reactive. T cells target myelin component. That plays a crucial role in mediating the inflammatory process, particularly MS (Steinmen 2001).
9. Multiple Sclerosis and T regular cell
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If a human immune system is attacked by a microbe, the invading microbe sends out a common genes sequence, that concords one of these conserve structural mortifies. The immune system, in recognising a structure found on the myelin sheath, this leads to an attack on myelin via a process called molecular mimicry. T cells also recognise the sequence react and bind sequences from the myelin sheaths that are shared with these microbial sequences (Steinmen 2001).
Theories suggest that due to a troubled balance in the cells the pathogenesis of autoimmune central nervous system inflames and this causes tissue damage, Demyelination. The integral components of the mechanisms that bring in and maintain peripheral tolerance are T regular cells and certain type of dendrite cells (Zozulya and wiendl 2008). Activated effectors T cells are able to hold back the function of self reactive T cells (Zozulya and wiendl 2008). Immunogenic dendrite cells have emerged as participants in the maintenance of immune reaction, these cells were directly responsible for the homeostasis of the central nervous system's immunity. Stimulated effectors T cell causing the inflammatory central nervous system demylination in the patients with MS were T cells travelling from the outside boundary across the blood-brain barrier (Zozulya and wiendl 2008). Under physiological condition, the regular T cells are in control of the auto reactive encephalitogenic effector T cells (Zozulya and wiendl 2008).
The animal model of Multiple sclerosis FOXP3 gene has been found to be a key regulatory molecule in the growth of thymine natural T regular cells and a genetic defect in the inducible ablutions of the FOXP3 gene, is an aggressive and lethal autoimmune disorder or immunodyregulation cells (Zozulya and wiendl 2008) (Borselling G et al 2007). T regular cell development requires continuous expression of FOXP3 regular. Loss of the T regular cell marker cytotoxic CTLA4, interleukin 2, interleukin-10 and GITP has also been found to correlate with immunopathogy (Zozulya and wiendl 2008).
Over the past few years, increasing number of studies have investigated the frequency and function of various T regular cell populations in patients with multiple sclerosis and in individuals without MS (Zozulya and wiendl 2008). In between patients with multiple sclerosis and healthy one, the frequency of CD4+ CD25 high T regular cells does not differ, though T regular cells are functionally weakened or have shortfall in their maturation or thymic emigration in patients with multiple sclerosis. In several of these researches, lymphocytes from patients with MS were stimulated with polyclonally, mitogen with anti-CD28 and anti-CD3 antigen or antibodies, in particular with MBP or MOG 45, and were analysed for their suppressive capacity (Zozulya and wiendl 2008). CD4+CD25 high T regular cells from patients with multiple sclerosis exhibited functional impairment. The primary defect in T regular-cell function in patients with multiple sclerosis was shown to be intrinsic to T regular cells. This could not be credited to a higher activation status or to resistance to inhibition of auto-reactive T cells (Zozulya and Wiendl 2008). Single-cell cloning experiments showed a reduced cloning frequency of CD4+CD25high T cells in patients with multiple sclerosis compared with healthy individuals (Zozulya and Wiendl 2008)( Huan et al. 2005).
The T regular cells play an important role in the inflammation of Central nerve system parenchyma (CNP) in response to both self and non-self antigens. Theoretically, T regular cells within the Central nerve system could combat harmful inflammatory components, thereby providing anti-inflammatory or Central nervous system-protective properties (Zozulya and wiendl 2008).
HLA-G-expressing T regular cells have newly been described as a novel natural T regular cell population in humans. These cells are found in small but significant quantities (0.1-4.0% of CD4+ T cells) in the marginal blood of healthy adults and were shown to be hypoproliferative, CD25- and FOXP3-, and have exhibited potent suppressive properties that are partially mediated by HLA-G and immunoglobulin-like transcript 2 (Zozulya and Wiendl 2008 ).
Multiple sclerosis is a permanent disease. It attacks the brain and spinal cord and slowly disables the patient. The cause of it could be environmental or genetic. Most of the patients with MS disorder are due to environmental reasons. In the body immune system works in opposition. Immune system T cells find the nervous as a foreign item. It is one of the autoimmune disorders where body's outline of protection become misguided and starts injuring normal cells, due to which myelin in the brain and spinal cord disintegrates (Borselling G et al 2007).
Different experiment with MS have so far proved that T-cells play an important role it the causes of multiple sclerosis disorders. But the route and why they attack myelin is yet unclear. So there is more work to be done to understand the proper role of T cell and prevention of MS.