Infections may activate self-reactive lymphocytes, thereby triggering the development of autoimmune diseases. Clinicians have recognized for many years that the clinical manifestations of autoimmunity sometimes are preceded by infectious prodromes. This association between infections and autoimmune tissue injury has been formally established in animal models. Infections may contribute to autoimmunity in several ways (Fig. 1):

Fig1. Mechanisms by which microbes may promote autoimmunity. A, Normally, an encounter of mature T cells with self antigens presented by resting tissue antigen-presenting cells (APCs) results in peripheral tolerance. B, Microbes may activate the APCs to express costimulators, and when these APCs present self antigens, the specific T cells are activated, rather than being rendered tolerant. C, Some microbial anti gens may cross-react with self antigens (mimicry). Therefore, immune responses initiated by the microbes may become directed at self cells and self tissues. This figure illustrates concepts as they apply to T cells; molecular mimicry also may apply to self-reactive B lymphocytes.

• An infection in a tissue may induce a local innate immune response, which may lead to increased production of costimulators and cytokines by tis sue APCs. These activated tissue APCs may be able to stimulate self-reactive T cells that encounter self antigens in the tissue. In other words, infection may break T cell tolerance and promote the activation of self-reactive lymphocytes. This may lead to disease if it occurs in people who are already genetically at risk or developing autoimmunity. One cytokine produced in innate immune responses to viruses is type I interferon (IFN). Excessive production of type I IFN has been associated with the development of several auto immune diseases, notably lupus. It may activate APCs or lymphocytes, but what stimulates its production and how it contributes to autoimmunity is not well understood.

 • Some infectious microbes may produce peptide antigens that are similar to, and cross-react with, self antigens. Immune responses to these microbial pep tides may result in an immune attack against self antigens. Such cross-reactions between microbial and self antigens are termed molecular mimicry. Although the contribution of molecular mimicry to autoimmunity has fascinated immunologists, its actual significance in the development of most autoimmune diseases remains unknown. In some disorders, antibodies produced against a microbial protein bind to self proteins. For example, in rheumatic fever, a fairly common disease before the widespread use of antibiotics, antibodies against streptococci cross-react with a myocardial antigen and cause heart disease.

 • The innate response to infections may alter the chemical structure of self antigens. For example, some periodontal bacterial infections are associated with rheumatoid arthritis. It is postulated that the inflammatory responses to these bacteria lead to enzymatic conversion of arginines to citrullines in self proteins, and the citrullinated proteins are recognized as non self and elicit adaptive immune responses.

• Infections also may injure tissues and release anti gens that normally are sequestered from the immune system. For example, some sequestered antigens (e.g., in testis and eye) normally are not seen by the immune system and are ignored. Release of these antigens (e.g., by trauma or infection) may initiate an autoimmune reaction against the tissue.

 • The abundance and composition of normal commensal microbes in the gut, skin, and other sites (the micro biome) may also influence the health of the immune system and the maintenance of self- tolerance. This possibility has generated a great deal of interest, but nor mal variations in the microbiome of humans related to environmental exposure and diet make it difficult to define the relationship between particular microbes and the development of autoimmune diseases.

Paradoxically, some infections appear to confer protection from autoimmune diseases. This conclusion is based on epidemiologic data and limited experimental studies. The basis of this protective effect of infections is unknown.

Several other environmental and host factors may contribute to autoimmunity. Many autoimmune dis eases are more common in women than in men, but how gender might affect immunologic tolerance or lymphocyte activation remains unknown. Exposure to sunlight is a trigger for the development of the autoimmune disease SLE, in which autoantibodies are produced against self nucleic acids and self nucleoproteins. It is postulated that these nuclear antigens may be released from cells that die by apoptosis as a consequence of exposure to ultraviolet radiation in sunlight. 

مواضيع ذات صلة

Genetic Factors of Autoimmunity

الحساسية الدوائية نحو العوامل المخصرة للوصل العَصَبِي العَضَلِي

آليات حساسية السلفوناميدات ومظاهرها

Antigen - Antibody Interaction: Specificity and Cross - Reactivity

ANTIBODY SYNTHESIS

Tolerance to Commensal Microbes and Fetal Antigens

B Lymphocyte Tolerance

Peripheral T Lymphocyte Tolerance

Immune Memory

B Cells

T Cells

إزالَةُ التَحسس نحو البنسلين Penicillin Desensitization