Lymphocytes autoimmunity

Wilkinson, P. C., Komai-Koma, M., and Newman, 1. (1997). Locomotion and chemo-taxis of lymphocytes. Autoimmunity 26, 55-72. 

Immunoglobulin D IgD 175000 y <0.15 [<100] Antibodies Surface receptors for antigen on B lymphocytes Autoimmune infections Chronic infections IgD myeloma Congenital deficit Childhood Acquired immunodeficiencies Non-lgD myeloma... 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

Ling Zhi-8 (LZ-8) is an immunomodulatory protein (29,30) isolated from the mycelial extract of Ganoderma lucidium, that has been purified and shown to stimulate mouse spleen and human peripheral blood lymphocytes. LZ-8 is able to inhibit antibody production and prevent the development of autoimmune type I diabetes in NOD mice. 

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). 

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. 

Multiple scelerosis is an autoimmune disease mediated by T and B lymphocytes and macrophages. This is characterized by extensive inflammation and demyelination of the myelin sheath that surrounds the nerve fiber. The death of the nerve fiber results in a variety of symptoms that can lead to impairment of movement, paralysis, and death. 

During differentiation of T- or B-lymphocytes antigen recqrtors are generated which react to self or autoantigens. These are generally eliminated by the mechanisms of central tolerance or kept silent by the mechanisms of peripheral tolerance ( autoimmune disease). 

The most common causes of hypothyroidism are listed in Table 41-2. Up to 90% of patients with autoimmune thyroiditis have circulating anti-TPOAbs. The autoimmune inflammatory response results in a lymphocytic infiltration of the thyroid gland and its eventual destruction. 

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

The function of the ALD protein is not fully understood, and knockout mice lacking it do not exhibit the severe CNS neurological deficits commonly associated with the human disease despite a similar accumulation of VLCFAs [26], Furthermore, the clinical variability in human patients cannot be accounted for by the severity of the biochemical abnormality or the nature of the gene defect. These observations, plus other data from mice with defects in VLCFA metabolism, raise the issue of whether the accumulation of VLCFAs in myelin is crucial to the pathological mechanisms or is an epiphenomenon. Unlike most other lipid-storage diseases, active ALD brain lesions are characterized by perivascular accumulation of lymphocytes. For this reason, it has been hypothesized that the severity of CNS pathology may relate to an autoimmune reaction that varies from patient to patient and... 

Painless (silent, lymphocytic, postpartum) thyroiditis is a common cause of thyrotoxicosis its etiology is not fully understood and may be heterogeneous autoimmunity may underlie most cases. 

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