Autoimmunity mechanisms

Pituitary failure (secondary hypothyroidism) is an uncommon cause resulting from pituitary tumors, surgical therapy, external pituitary radiation, postpartum pituitary necrosis, metastatic tumors, tuberculosis, histiocytosis, and autoimmune mechanisms. 

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. 

El Fawal, H.A.N. et al., Neuroimmunotoxicology Humoral assessment of neurotoxicity and autoimmune mechanisms, Environ. Health Perspect 107, 767, 1999. 

Talal, N. (1998). Autoimmune mechanisms in patients and animal models. Toxicol. Path. 15 272-275. 

The precise mechanism involved in loss of body fat in this disorder however remains speculative but it is likely that autoimmune mechanisms (body defense mechanisms acting against body fat) are involved. Interestingly, in AGL severe insulin resistant diabetes mellitus is a typical clinical feature." Insulin resistance is frequently associated with an increased body weight and fat mass. Therefore, AGL is an interesting and unique knockout model of subcutaneous adipose tissue combined with insulin resistant diabetes mellitus. 

Autoimmune mechanisms are blamed for the destruction of pancreatic p cells in overt type 1 diabetes. The exact means, however, by which this selective destruction occurs in humans is unknown (Atkinson and Maclaren, 1994). In order to gain an insight into the human disease, various animal models have been developed and extensively studied the often investigated one being the non-obese diabetic (NOD) mouse (Atkinson and Leiter, 1999). 

The typical pancreatic lesion of type 1 diabetes is the selective loss of almost all 3-cells, whereas other islet cell types (a, 8, and pancreatic polypeptide cells) remain intact. The most common mechanism for 3-cell destruction is thought to be autoimmune-mediated inflammatory damage. Prospective family studies strongly support a genetic basis for susceptibility to this autoimmune process and suggest that the underlying immune abnormalities precede clinical insulin deficiency by many years. However, not all spontaneous type 1 diabetes is the result of autoimmune mechanisms. 

The neurologic involvement in Crohn s disease can be attributed to several mechanisms including autoimmunity. For the predominant arterial cerebrovascular involvement, the state of hyper coagulation secondary to thrombocytosis and increase in factor V, Vm and fibrinogen are probable mechanisms. However, since anti-phospholipid antibodies and lupus anticoagulant are confirmed in many cases, autoimmune mechanisms are also involved (Santos et al., 2001). 

Liver damage has been attributed to black cohosh, which contains diterpenoids that cause hver damage in animals, either via reactive metabolites or by an autoimmune mechanism. However, causahty was not demonstrated beyond reasonable doubt. 

The cause of this condition is unknown, but an autoimmune mechanism triggered by endogenous and exogenous factors has been suggested. 

Thrombocytopenia can be caused by autoimmune mechanisms (SED-13, 150) (54), tends to be related to high serum drug concentrations, and often responds to dosage reduction (SEDA-19, 74). Of 131 patients randomized to high plasma concentrations of valproic acid (80-150 gg/ml), 36 (27%) had at least one platelet count below 75 X 10 /1, compared with only one patient in a group randomized to drug concentrations of 25-50 gg/ml (55). 

Several etiologic factors are implicated as the cause of RPGN toxins, drugs, viral and bacterial infections, neoplasms, autoimmune mechanisms, and various immunogenetic factors. ... 

TSH is required for normal thyroid secretion. Thyroid atrophy and decreased thyroid secretion follow pituitary failure. Pituitary insufficiency may be caused by destruction of thyrotrophs by either functioning or nonfunctioning pituitary tumors, surgical therapy, external pituitary radiation, postpartum pituitary necrosis (Sheehan s syndrome), infiltrative processes of the pituitary such as metastatic tumors, tuberculosis, histiocytosis, and autoimmune mechanisms. In all these sitnations, TSH deficiency most often occurs in association with other pituitary hormone deficiencies. 

The severity of drug-induced immune hemolytic anemia is usually a function of the rate of hemolysis. Hemolytic anemia caused by drugs via the hapten/adsorption and autoimmune mechanisms tend to be slower in onset and mild to moderate in severity. Conversely, hemolysis prompted via the neoantigen mechanism (innocent bystander) phenomenon may have a sudden onset, lead to severe hemolysis, and result in renal failure. The treatment of drug-induced immune hemolytic anemia includes the removal of the offending agent and supportive care. Glucocorticoids are usually unnecessary, and practitioners have questioned their efficacy. ... 

Individuals who are prone to develop autoimmune responses may be susceptible to the development of EMS due to implicated L-tryptophan. Many investigators who reviewed cases of EMS have suggested that an autoimmune mechanism was involved in EMS.50114-116 Some experimental studies with contaminants or impurities of implicated L-tryptophan have proposed mechanisms whereby abnormal proteins may be formed that may elicit an autoimmune response, with major consequences thereof.64 6598 Patients with EMS have increased levels of plasma neopterin, a marker of immune activation.58... 

INTRODUCTION TO THE IMMUNE SYSTEM FOCUS ON AUTOIMMUNE MECHANISMS... 

Autoimmune diseases include a wide variety of illnesses targeting many sites in the body. They form an important health problem, affecting at least 5% of the population. Furthermore, autoimmune mechanisms play a role in many other diseases hence, more than these 5% will encounter autoimmune-associated health effects. 

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