T cell attack

Most cells of the immune system are ordinarily kept apart from those of the nervous system by means of the blood-brain barrier. However, allergic encephalomyelitis, in which T cells attack the myelin sheath of brain neurons, can easily be induced in mice.506 A similar autoimmune process is thought to be involved in human multiple sclerosis (see Chapter 30, pp. 1769, 1808, and Fig. 30-9).507,508 High levels of circulating IgM are found in some demyelinating diseases of peripheral neurons.508 In Rasmussen s encephalitis, which causes brain inflammation and epilepsy, serum antibodies attack a glutamate receptor subunit GluR3.509... 

Prior research has shown that both /3-cells and T-cells act to initiate type 1 diabetes. T-cells attack and destroy the insulin-producing /S-cells. /S-cells don t directly attack insulin-producing cells, but may trigger the T-cells to attack. Rituximab, a chimeric monoclonal antibody against CD20, found primarily on the surface of /S-cells, has shown potential in delaying the development of type 1 diabetes. 

T cells are further divided into three primary classes helper T cells (T-H cells), cytotoxic T cells (ctx T cells), and T suppressor T cells. T-H cells augment B cell responses to bacterial antigens. Cytotoxic T cells attack viral antigens and some early cancer cells. And suppressor T cells halt immune cell functions, allowing the body to rest. 

The immune system does mount a vigorous response in these early days. Macrophages ingest the viral particles and degrade them, and then display small portions of the virus (small peptides called epitopes) on their surface, and this attracts the attentions of helper T-cells, which in turn activate killer T-cells and B-lymphocytes. The killer T-cells attack cells displaying the viral epitopes, and the B-cells produce dedicated antibodies that also seek out and destroy such cells. Not surprisingly, in the early days after infection, around 30% of patients exhibit typical symptoms of their immune response to viral... 

Helper T2 cells—increase activity of cytotoxic (killer) T cells, which attack the cell directly by altering the cell membrane and causing cell lysis (destruction)... 

Over 20 infectious agents have been incriminated as etiologic agents for many the causal relationship has been disproved, and for others there is conflicting evidence. Human herpesvirus 6 (HHV-6) is currently the most likely causative virus. HHV-6 may initiate the autoimmune processes of MS in one of two ways. First, HHV-6 is structurally similar to myelin basic protein. When T cells become sensitive to HHV-6, the cells may attack myelin basic protein. Second, HHV-6 may directly stimulate the complement cascade, activating autoimmune processes.5 Infection with HHV-6 alone cannot fully explain MS, because HHV-6 is found in 75% of all people, but MS is much more rare. 

T cell and cytokine regulation of enterocyte apoptosis may also be important in the expulsion of nematodes, in particular T. spiralis and T. muris, which inhabit an intracellular niche. Certainly an increase in the number of apoptotic cells within the epithelium is observed around the period of expulsion of T. muris in resistant mouse strains (D. Artis, C.S. Potten and R.K. Grencis, unpublished). Apoptosis of host enterocytes may dislodge the nematode or perhaps expose vital feeding organs to immune attack, and so enhance expulsion. Whether enterocyte apoptosis results from the burrowing action of the worms or a tissue repair mechanism, or is involved in expulsion, remains to be investigated. 

What is not clear is the specificity of the T cells. There are numerous studies of T cell reactivity to myelin antigens such as MBP, PLP and MOG, all of which are enceph-alitogenic in animals. However, the evidence taken as a whole has failed to demonstrate a substantially increased response to these antigens in most patients with MS compared to healthy controls. Nevertheless, at this time, MOG appears to be a leading candidate among myelin proteins to be an important target in the autoimmune aspects in many patients because of (1) its accessibility to immune attack due to its surface localization on oligodendrocytes ... 

Calcineurin is a serine/threonine protein phosphatase widely distributed in the brain, but its role in brain function remains unknown. It is critical for several important cellular processes including T-cell activation, and recent data indicate that it may be involved in hyperphosphorylation of tau in Alzheimer s disease (600, 601). The active site of native calcineurin contains zinc and iron metal ions and three metal-bound water molecules (602), one of which may be involved in nucleophilic attack on the substrate. Compound 119 (FK506, tacroli-... 

One of the important relay stations in the immune system activation is the dendritic cell. Activation of these cells causes the most efficient stimulation of T-cells, which in turn attack tumor cells (9). This turned the dendritic cells (DCs) into the focus of modern immune research and therapy. However, another difficulty appeared that became a problem recently. In order to activate the dendritic cell, the antigen has to be present in the cytosol and has to be processed there further this is not an easy task to perform. 

Trophoblast cells do not produce MHC proteins, so that foetal peptides cannot be expressed on their surface to direct an attack by cytotoxic T-cells (Chapter 17). 

III210 are found in granules of neutrophils and monocytes as well as in mast cells.209 Cytoplasmic granules of cytotoxic T cells contain at least seven proteases called granzymes that can be released to attack target... 

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