Autoimmune processes

In the pathogenesis of many chronic inflammatory diseases (e.g., rheumatoid arthritis, glomerulonephritis, colitis ulcerosa, Morbus Crohn, atopic dermatitis, psoriasis) autoimmune processes play an important role, too. Although first of all nonsteroidal antiinflammatory agents or glucocorticoids should be applied, immunosuppressive agents may also be indicated. 

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. 

The therapeutic goal in autoimmune diseases such as RA is to control disease, to establish remission, and eventually to cure. In theory, this goal can be achieved using either Ag-specific approaches, for example, elimination of self-reactive T cells (assuming that a finite number of key Ags can be identified as the target of the autoimmune process in RA), or the non-Ag-specific approaches, for example, blockade of cytokines as in the case of TNF-a neutralization. Currently, only the latter types of approaches have yielded clinical benefit, and it is in this category that approaches to block chemokines or receptors may be included. Despite their appeal in terms of effectiveness, non-Ag-specific approaches carry a higher risk of immunosuppression and opportunistic infections (48). 

The cause of MS is not known, but most evidence points to an immunologically mediated disease with important genetic and environmental risk factors [ 1,2,7,8]. The evidence for an autoimmune process is largely circumstantial... 

The hypocretin/orexin neurotransmitter system may play a central role in narcolepsy. An autoimmune process may cause destruction of hypocretin-producing cells. 

In Graves disease, the autoimmune processes mediate the enlargement of the thyroid gland, the infiltrative ophthalmopathy with exophthalmos, and the dermopathy and thereby distinguish Graves disease from other causes of thyrotoxicosis. 

The other type of diabetes mellitus, type II, is far more common. In contrast, type II is not an autoimmune process and may or may not be insulin dependent that is, a diabetic state that is most effectively managed by insulin therapy. Frequently, NIDDM is used interchange-... 

Mechanism of Action A DMARD that inhibits dihydroorotate dehydrogenase, the enzyme involved in autoimmune process that leads to rheumatoid arthritis. Therapeutic Effect Reduces signs and symptoms of rheumatoid arthritis and slows structural damage. 

In the last few years there has been increased interest in the immune aspects of OCD and related disorders. It has been proposed that some cases of childhood-onset OCD may be related to an infection-triggered autoimmune process similar to that of Sydenham s chorea, a late manifestation of rheumatic fever (Swedo, 1994 Chapter 14, this volume). 

Sheiman B, Osadchaya O, Boyarskaya G et al (2007) Use of enterosorption for prophylaxis of autoimmune processes in patients with severe bums. Klinichna Imunologiya, Alergologiya, Infectologiya 3 104—106 (In Russian)... 

Cell destruction during the development of IDDM is the result of autoimmune processes. Considerable evidence supports the autoimmune nature of IDDM. This evidence includes (1) observation of lymphocyte infiltration into pancreatic islets in biopsy specimens taken from patients in early stages of IDDM (2) the identification of islet-cell autoantibodies from patients with IDDM ... 

A low titer of circulating IgG anti-insulin antibodies that neutralize the action of insulin to a negligible extent develops in most insulin-treated patients. Rarely, the titer of insulin antibodies leads to insulin resistance and may be associated with other systemic autoimmune processes such as lupus erythematosus. 

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... 

Reactivation of the autoimmune process may occur when the dosage of antithyroid drug is lowered during maintenance therapy and TSH begins to drive the gland. TSH release can be prevented by the daily administration of 50-150 ag of levothyroxine with 5-15 mg of methimazole or 50-150 mg of propylthiouracil for the second year of therapy. The relapse rate with this program is probably comparable to the rate with antithyroid therapy alone, but the risk of hypothyroidism and overtreatment is avoided. 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

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. 

Transplantation of islets of Langerhans as a means of treating insulin-dependent diabetes mellitus has become an important field of interest [217-219]. However, tissue rejection and relapse of the initial autoimmune process have limited the success of this treatment. Immunoisolation of islets in semipermeable microcapsules has been proposed to prevent their immune destruction [220, 221]. Nevertheless, a pericapsular cellular reaction eventually develops around micro-encapsulated islets, inducing graft failure [222]. Since empty microcapsules elicit a similar reaction [223], the reaction is not related to the presence of islets within the capsule but is, at least partially, caused by the capsule itself. Consequently, microcapsule biocompatibility appears to constitute a major impediment to the successful microencapsulated islet transplantation. 

Qll There is both a genetic and environmental component in type 1 diabetes. The pathological basis of the condition is autoimmune destruction of the pancreatic islet cells, which is said to be associated with genetic and environmental factors such as viral infection. It has been shown that antibodies to islet cells and insulin autoantibody (IAA) can exist for years before the occurrence of symptoms, possibly as a result of the autoimmune processes the IAA may form during the process of active islet and /1-cell destruction. Both insulin and glucagon play a role in the development of hyperglycaemia and hyperketonaemia, since both a- and /1-cell functions are abnormal in diabetes. Both a lack of insulin and a relative excess of glucagon coexist in type 1 diabetes, and so the metabolic abnormalities that occur are likely to be caused by both hormones. 

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