The factors that contribute to the development of autoimmunity are genetic susceptibility and environmental triggers, such as infections and local tissue injury. Susceptibility genes may disrupt self-tolerance mechanisms, and infection or necrosis in tissues promotes the influx of autoreactive lymphocytes and activation of these cells, resulting in tissue injury (Fig. 15–11). Infections and tissue injury may also alter the way in which self-antigens are displayed to the immune system, leading to failure of self-tolerance and activation of self-reactive lymphocytes.
1. Immunologic Abnormalities
Autoimmunity results from some combination of three main immunologic aberrations: Defective tolerance or regulation. Failure of the mechanisms of self-tolerance in T or B cells, leading to an imbalance between lymphocyte activation and control, is the underlying cause of all autoimmune diseases; Abnormal display of self-antigens. Abnormalities may include increased expression and persistence of self-antigens that are normally cleared, or structural changes in these antigens resulting from enzymatic modifications or from cellular stress or injury. If these changes lead to the display of antigenic epitopes that are not present normally, the immune system may not be tolerant to these epitopes, thus allowing anti-self-responses to develop; Inflammation or an initial innate immune response. Infections or cell injury may elicit local innate immune reactions with inflammation. These may contribute to the development of autoimmune disease, perhaps by activating APCs, which overcomes regulatory mechanisms and results in excessive T cell activation.
2. Genetic Basis
Most autoimmune diseases are complex polygenic traits in which affected individuals inherit multiple genetic polymorphisms that contribute to disease susceptibility, and these genes act with environmental factors to cause the diseases. Among the genes that are associated with autoimmunity, the strongest associations are with MHC genes.
3. Role of Infections
Viral and bacterial infections may contribute to the development and exacerbation of autoimmunity. In patients and in some animal models, the onset of autoimmune diseases is often associated with or preceded by infections. In most of these cases, the infectious microorganism is not present in lesions and is not even detectable in the individual when autoimmunity develops. Therefore, the lesions of autoimmunity are not due to the infectious agent itself but result from host immune responses that may be triggered or dysregulated by the microbe. Infections may promote the development of autoimmunity by two principal mechanisms: Infections of particular tissues may induce local innate immune responses that recruit leukocytes into the tissues and result in the activation of tissue APCs. These APCs begin to express costimulators and secrete T cell activating cytokines, resulting in the breakdown of T cell tolerance. Thus, the infection results in the activation of T cells that are not specific for the infectious pathogen; this type of response is called bystander activation. Infectious microbes may contain antigens that cross react with self-antigens. So immune responses to the microbes may result in reactions against self-antigens. This phenomenon is called molecular mimicry because the antigens of the microbe cross react with, or mimic, self-antigens.
Figure 1. Role of infections in the development of autoimmunity. (a) Microbes may activate the APCs to express costimulators, and when these APCs present self-antigens, the self-reactive T cells are activated rather than rendered tolerant. (b) Some microbial antigens may cross-react with self-antigens (molecular mimicry). Therefore, immune responses initiated by the microbes may activate T cells specific for self-antigens.
4. Other Factors
Anatomic alterations in tissues, caused by inflammation (possibly secondary to infections), ischemic injury, or trauma, may lead to the exposure of self-antigens that are normally concealed from the immune system. Hormonal influences play a role in some autoimmune diseases.
5. Autoimmune Disease
From a clinical perspective it is often useful to distinguish between the following two major patterns of autoimmune disease: the diseases in which the expression of autoimmunity is restricted to specific organs of the body, known as ‘organ-specific’ autoimmune diseases; and those in which many tissues of the body are affected, the ‘systemic’ autoimmune diseases. In both types of autoimmunity, disease has a tendency to become chronic because, with a few notable exceptions (for example type 1 diabetes or Hashimoto’s thyroiditis), the autoantigens are never cleared from the body (Figure 2).
Details See Autoimmune Disease Guide from Our Resource Library
Figure 2. Organ specific and systemic autoimmune disease.
Autoimmune diseases are among the most challenging scientific and clinical problems in immunology. The current knowledge of pathogenic mechanisms remains incomplete, so theories and hypotheses continue to outnumber facts. The application of new technical advances and the rapidly improving understanding of self-tolerance will, it is hoped, lead to clearer and more definitive answers to the enigmas of autoimmunity.
Browse All Products Related to Autoimmune ELISA kit at Creative Diagnostics.
Article source: https://www.creative-diagnostics.com/Autoimmunity.htm.
References:
1.
Murphy K M. Janeway’s immunobiology [M]. Garland Science, 2011.
2.
Abbas A K, Lichtman A H H, Pillai S. Cellular and Molecular Immunology: with STUDENT CONSULT Online Access [M]. Elsevier Health Sciences, 2014.