Immune complexes (IC) are integral to the pathogenesis of several autoimmune diseases, including SLE and RA. The prototypic experimental model of soluble IC disease, the Arthus reaction, has served as the basis for dissecting the cellular and molecular events triggered by IC deposition and serves as the basis for our understanding of the pathophysiology of IC— mediated diseases.
Diseases can be characterized as autoimmune by direct, indirect, and circumstantial evidence (Timby and Smith, 2006 p. 350). Direct evidence is given by the presence of disease-specific autoantibodies (AABs) and/or autoreactive T cells that cause organ dysfunction and/or chronic inflammation (Meyers, 1995 p. 56). Animal models with spontaneously developed or induced diseases that resemble autoimmune diseases (AIDs) in humans may provide indirect evidence.
Circumstantial evidence includes the association with other autoimmune conditions, the presence of AABS (regardless of their pathogenic role), the association with major histocompatibility complex (MHC) kaplotypes, the infiltration of lymphocytes into target organ(s), germinal centers in the lesions, infiltrating lymphocytes with restricted V-gene usage, and favorable response to immunosuppression (Meyers, 1995 p. 54). The etiologies and pathological mechanisms involved in the development of Al Ds are incompletely understood.
There is no doubt that genetic as well as environmental factors are responsible for the induction, development, and progression of autoimmune diseases. According to clinical manifestations and autoimmune responses. Autoimmune diseases may be considered organ-specific or non-organ- specific (systemic) (Timby and Smith, 2006 p. 349). Physiology and the Effects of Autoimmunity Physiologically, the host’s immune system does not react destructively towards a tissue antigen present on it won cell membranes. Self-antigens may be termed induce a hostile response.
Tolerance is thus the converse of immunity, and autoimmunity follows when the mechanisms governing self-non responsiveness and the ability of the immune system to distinguish tolerogens from immunogens are disrupted (Pollard, 2006 p. 215). Systemic autoimmune diseases represent a very heterogeneous group of autoimmune diseases with manifestations on multiple tissues or organs and include rheumatoid arthritis, connective tissue diseases (CTDs), antiphospholipid syndrome, and systemic vasculitides (Motze and Thomson, 2001 p. 219).
The CTDs can be classified as systemic lupus erythematosus, systemic sclerosis, Sjogrens syndrome (SjS), idiopathic inflammatory myopathies, as well as various overlap syndromes and undifferentiated CTDs. Even within a defined disease entity, there is large heterogeneity, and hence added complexity. regarding clinical manifestations, genetic background, and autoantibody profiles. Autoimmune diseases are clinically very diverse and, in many instances, the diagnosis is based on the presence of several clinical signs and symptoms among a predefined set.
The clinical presentation of drug-induced autoimmune reactions is more or less variable with respect to the spontaneous disease so that the presence of antibodies in the sera of patients is a prerequisite. It has been proposed that dendritic cells (DCs) are the critical decision-making cells in the immune system. Through their role In the generation of central and peripheral tolerance, as well as in priming immune responses and stimulation of memory and effector T cells, DCs are liely to play essential roles In the initiation and perpetuation of autoimmunity and autoimmune diseases (Pollard, 2006 p.214).
Organ-specific autoimmune reactions induced by xenobiotics are characterized by homogenous antibody response against a unique target (resulting in the presence of predominant types of autoimmunity in the sera of affected patients) and by clinical symptoms closely mimicking those found in the corresponding spontaneous autoimmune diseases (Motze and Thomson, 2001 p. 217). Loss of tolerance in self-antigens is necessary for generation of autoimmunity. Tolerance is actively maintained centrally in the thymus.
T cells reactive to self-antigens presented by medullary DCs are deleted by negative selection above a threshold of affinity for the antigen . In the periphery, tolerance may be active, through deletion or regulation of sell-reactive T cells, or passive, due to ignorance of certain sell-antigens. Peripheral self-reactive T cells may be controlled in a number of ways (Motze and Thomson, 2001 p. 218). Deletion of self-reactive cells has been shown to occur in lymph nodes draining uninflamed peripheral organs and tissues.
In other circumstances, T-cell receptor (TCR) signaling may lead to functional unresponsiveness or anergy (Eales, 2003 p. 76). There are a number of diseases that clearly have autoimmune reactions as component and specific and her diseases the relationship is less clear. The level of autoantibodies increases with age, and it is quite common to find older people whose sera test positive for autoantibodies, but who show no signs of any corresponding clinical disease (Eales, 2003 p. 78).
Although humans develop autoantibodies with age, autoimmune diseases do not increase in frequency (Motze and Thomson, 2001 p. 219). The most conspicuous autoimmune conditions are probably thyrotoxicosis, systemic lupus, myasthenia gravis, and autoimmune hemolytic anemia, none of which is commonly associated with old age (Brown and Faust, 2004 p. 415). Thus, autoimmune diseases do not appear to be diseases characteristic of old age but arc more likely due to a genetic predisposition to the autoimmune disease.
There is evidence that diseases that are either generally accepted as autoimmune in character or have some other immunopathological quality show significant correlations with a given histocompatibility antigen (Eales, 2003 p. 76). Conclusion Autoimmune disorders produce various signs and symptoms depending on the tissues and organs affected. The symptoms are characteristic of an acute inflammatory response. They develop as antibodies attack normal tissue mistakenly identified as oneself.
In some cases, the inflammatory symptoms are episodic periods of acute flare-ups (known as exacerbations) alternate with periods of remission (asymptomatic periods). The duration of these periods is completely unpredictable, and during acute exacerbations, clients often experience a low-grade fever, malaise, or Fatigue. They also may lose weight.
Reference
Brown, S. P. , & Miller, W. C. (2006). Exercise Physiology: Basis of Human Movement in Health and Disease. Lippincott Williams & Wilkins. Brown, S. P. , Faust, R. , & Buyon, J. P. (2004). The Autoimmune Connection: Essential Information for Women. McGraw-Hill Professional.