Autoimmune reaction

Blood sugar (blood glucose) in human beings is controlled by the secretion of (—>) insulin by the beta (B- or (3-) cells of the islands of Langerhans in the pancreas. Loss of insulin synthesis leads to (—>) diabetes. Type 1 diabetes (insulin dependent diabetes mellitus, EDDM) begins in juveniles as an organ-specific autoimmune reaction, the destructive insulitis. 

Interferon beta-la (AVONEX , Rebif ), interferon beta-lb (Betaferon ), and interferon beta (Fiblaferon ) are applied in multiple sclerosis to reduce both frequency and severity of disease incidents and for the treatment of severe viral infections. In multiple sclerosis, DFN- 3 proteins modulate the destruction of myelin in the cause of the autoimmune reaction. 

In some instances more severe side effects are noted (Table 8.11), whereas in a few cases very serious side effects, such as induction of autoimmune reactions and central nervous system or cardiovascular disturbances, render necessary immediate withdrawal of treatment. 

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... 

In open-angle glaucoma, the specific cause of optic neuropathy is unknown. Increased intraocular pressure (IOP) was historically considered to be the sole cause. Additional contributing factors include increased susceptibility of the optic nerve to ischemia, reduced or dysregulated blood flow, excitotoxicity, autoimmune reactions, and other abnormal physiologic processes. 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Druet, P. et al., Autoimmune reactions induced by metals, in Autoimmunity and Toxicology Immune Dysregulation Induced by Drugs and Chemicals, Kammunller, M.E., Blocksma, N., and Seinen, W., Eds., Elsevier, Amsterdam, 1989, 347. 

Drugs can cause a wide variety of other autoimmune reactions. One example is myasthenia gravis, which is characterized by muscle weakness and is mediated by antibodies against the acetylcholine receptor at the neuromuscular junction. It has been reported in association with penicillamine [66], gold salts [67], and procainamide [68]. Another form of drug-induced autoimmunity is polymyositis, which is an autoimmune disease... 

Griem, P. et al., Allergic and autoimmune reactions to xenobiotics How do they arise , Immunol. Today, 19, 133, 1998. 

Development of models to assess chemical-induced allergic or autoimmune reactions is difficult in that both types of reactions are subject to complex processes, and are idiosyncratic in nature. Factors that must be considered include a large number of genetic as well as phenotypic, neuroendocrine, or environmental factors that are only in part related to the immune system. 

Balazs, T.Jmmunogenetically controlled autoimmune reactions induced by mercury, gold and D-penicillamine in laboratory animals A review from the vantage point of premarketing safety studies. Toxicol. Ind. Health., 3, 331, 1987... 

Weltzien, H.U., et al., T cell immune responses to haptens. Structural models for allergic and autoimmune reactions. Toxicology, 107, 141, 1996. 

The latest methods for detecting and characterizing the potential for industrial chemicals and drugs to induce hypersensitivity and autoimmune reactions... 

Irreversible inhibition of CYPs is particularly worrisome as its consequences cannot be predicted easily or quantified from in vitro data the in vivo effect of an irreversible inhibitor is usually greater than that predicted based on affinity alone. Moreover, irreversible inhibition is generally the consequence of the production of reactive metabolites (electrophiles), which can also bind covalently to endogenous proteins and, in rare cases, trigger serious autoimmune reactions [4]. 

Mayer C. Appenzeller U. Seelbach H. Achatz G. Oberkofler H. Breitenbach M. Blaser K. Crameri R Humoral and cell-mediated autoimmune reactions to human acidic ribosomal P2 protein in individuals sensitized to Aspergillus fumigatus P2 protein. J Exp Med 1999 189 1507-1512. 

DR on T cells, B cells and synovial lining cells, indicating strong immunological activity. RA is thought to be an autoimmune reaction, caused by an interaction between constitutional and environmental factors [14]. 

Autoimmune diseases are another important area of substance-induced immunotoxicity. At present there are no specific assays to assess substances for their potential to induce autoimmune reactions (EC 2003). 

Diabetes mellitus is a very common metabolic disease that is caused by absolute or relative insulin deficiency. The lack of this peptide hormone (see p. 76) mainly affects carbohydrate and lipid metabolism. Diabetes mellitus occurs in two forms. In type 1 diabetes (insulin-dependent diabetes mellitus, IDDM), the insulin-forming cells are destroyed in young individuals by an autoimmune reaction. The less severe type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) usually has its first onset in elderly individuals. The causes have not yet been explained in detail in this type. 

Range of flu-like S5miptoms, e.g. fever, headache, chills Anorexia Strong fatigue Insomnia Cardiovascular complications Autoimmune reactions Hepatic decompression... 

A number of drugs and environmentally and occupationally important chemicals can impair the activity of one or more components of the immune system. Immunodeficiency may result in increased susceptibility to infection, decreased surveillance against precancer-ous or cancerous cells, or tissue-damaging reactions (Table 7.1). Allergic and autoimmune reactions are examples of this form of toxicity. 

Autoimmune reactions associated with a-methyldopa treatment include thrombocytopenia and leukopenia. Since a few cases of an a-methyldopa-induced hepatitis have occurred, the drug is contraindicated in patients with active hepatic disease. FluUke symptoms also are known to occur. 

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