T-lymphocyte

T cells exist as three separate subsets of cells  

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Interfaces play a predominant role in metabolic processes [78], as well as in immune recognition (e.g. T lymphocytes recognizing antigens on the surface of antigen presenting cells, section c2.14.6.2. Historically, the bulk of experimental... 

T-Lymphocytes (4,5) and other cellular components of the immune system also have equally wide implications in regulation of the normal immune system. The T-lymphocytes play a central role in the body s response to harmful antigens and tumor—host interaction (4). Responses involve antigens derived from vimses, bacteria, parasites, and tumors. T-ceUs also participate in the immune surveillance response, where self-antigens are recognized, but usually sequestered within the cell and, when exposed, become markers of cellular damage. 

The pathogenesis of AIDS (10,12,13) following HIV infection may be separated into primary and secondary effects. The primary effects are (/) quantitative and quahtative decreases in infected cells, ie, the T-lymphocytes (2) impaked cellular immunity (J) impaked immune surveillance and... 

Gradual diminution of 004 T-lymphocytes from the peripheral blood is the most consistent feature observed in HIV infection. Because the majority of 004 cells are T-helper lymphocytes, removal leads to deficiency of cellular immunity, which depends on T-helper cells to initiate cytotoxic T-ceU killing of vims-infected cells of cancer. The loss of immune surveillance leads to the appearance of viraHy induced tumors from unopposed clonal expansion of viraHy transformed cells. Furthermore, depletion of cellular immunity leads to exaggerated viral, fungal, and proto2oal infections. 

Human Immunodeficiency Virus. Human immunodeficiency vims (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which has no cure. HIV infects the cells of the human immune system, such as T-lymphocytes, monocytes, and macrophages. After a long period of latency and persistent infection, it results in the progressive decline of the immune system, and leads to full-blown AIDS, resulting in death. 

Restricted Cytotoxic T-Lymphocyte Responses," Biomedicine 96 Medical Research from Bench to Bedside, Washiagton, D.C., May 3—6, 1996. 

In this type of reaction an antigen elicits the generation of cytotoxic T-lymphocytes ( immune defense). Cytotoxic T-lymphocytes (Tc) destroy antigen bearing cells by inducing apoptosis. This reaction can be viewed as the cellular counterpart to the humoral Type II reactions. They play an important physiological role in the defense of viruses, and can become allergic reactions under the same conditions as described for Type II reactions. 

Antigens commonly induce the activation of T-lymphocytes of the T helper type (Th). In the case of Type IV b reactions the predominant responding cell is the Th-1 subtype. By secreting many cytokines, including... 

T-cells, representing the adaptive arm of the immune response, also play a critical role in atherogenesis, and enter lesions in response to the chemokines inducible protein-10 (DP-10), monokine induced by DFN-y (MIG), and DFN-inducible T-cell a-chemoattractant (I-TAC), which bind CXCR3 (a chemokine receptor containing two cysteine residues separated by one amino acid), highly expressed by T lymphocytes in the plaque. The... 

Part of these T-lymphocytes transform into memory cells. These cells are different from their ancestors in that they are activated by a much lower antigen binding strength and also much less depend on signal 2. Now self-antigens can activate these T-lymphocytes. As during activation continuously new memory cells are formed, autoreactivity is sustained and autoimmune disease follows (Fig. 2). 

Although this may suffice, additional factors contribute to this process. Activated T-lymphocytes secrete amongst other cytokines also interferon y which... 

Autoimmune Disease. Figure 1 Mechanisms of self tolerance. DC, dendritic (antigen presenting) cell T, T-lymphocyte Th, T helper lymphocyte Treg, T regulatory lymphocyte. For details see text. 

Autoimmune Disease. Figure 2 Generation of autoreactivity. APC, antigen presenting cell IFN, interferon LPS, lipopolysaccharide MHC, major histocompatibility complex T, T-lymphocyte TCR, Tcell (antigen) receptor TLR, toll like receptors. For details see text. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Interleukin 2 (Aldesleukin, Proleukin ) is a major growth factor and activator of cytotoxic and other T-lymphocytes. It is applied in the therapy of metastas-ing renal carcinoma and melanoma. Side effects include... 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Humanized recombinant anti-IL-2 receptor antibodies (Basiliximab, Simulect , and Daclizumab Zenapax ). These antibodies bind with high affinity to the IL-2 receptor on T-lymphocytes and prevent activation and clonal expansion of anti-allograft T-lymphocytes by endogenous IL-2. They are used to prevent kidney allograft rejection. The main side effect is immunosuppression. 

Delayed type hypersensitivty (DTH) reactions (synonym type IV allergic reactions) are exaggerated, T-lymphocyte mediated, cellular immune reactions to foreign substances, which require one to two days to manifest clinical symptoms. 

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