Autoimmune disease
Autoimmune disease in medicine is an umbrella term for diseases caused by an overreaction of the immune system against the body's own tissues. Mistakenly, the immune system recognizes the body's own tissues as foreign bodies to be controlled. This leads to severe inflammatory reactions that lead to damage to the affected organs.
Definition
The immune system is responsible for the detection and prevention of foreign substances, microorganisms and viruses; play an important role T- cells that are " trained " in the thymus to dock with their own MHC molecules and to tolerate the body's own structures.
This process is called " clonal deletion "; wherein the positive selection in the thymus, only those T cells survive that recognize MHC molecules on the endogenous cell membranes. T- cells, which own MHC molecules do not bind (ie recognize ) can be eliminated. In negative selection also takes place in the thymus after those T - cells are eliminated, can bind so tightly the body's own MHC molecules that they are activated - which would ultimately lead to the destruction of the body's own cells.
This central immune tolerance is one of those measures taken by the immune system to " itself " protect and to fight "foreign ".
In autoimmune diseases, a group of T cells behave differently. Cells of the immune system now recognize the body's own structures as foreign. The immune system directs his defense (cellular as well as humoral defense reactions; autoantibodies are formed ) against the body's own tissues, while repair mechanisms of the body possible, try to renew the damaged organ parts. This erroneous attack of the immune system continues without treatment is usually life-long, or up to complete destruction of the target structure continues.
MHC molecules
The human organism can distinguish between self and non- protein molecules (such as bacteria, viruses or worms ); the body must therefore have self- recognition proteins. To distinguish the key role that MHC proteins (English Major Histocompatibility Complex). With the help of these membrane proteins the immune system recognizes foreign cells. There are two types of MHC proteins, Class I proteins (HLA- class I molecules ) are present on all nucleated cells of the body. MHC class II molecules (HLA class II ) molecules are, however, present only on the surface of antigen- presenting cells (such as macrophages).
Class I and II MHC molecules encoded by genes 13 and 14, all of which are other than β2 -microglobulin in the HLA locus on chromosome 6. These genes are polymorphic, that is, at the population level, a large number of different alleles exist. Therefore, two widely related people rarely offer the same set of MHC proteins. Since the MHC proteins (except erythrocytes) on the surface of nearly all cells encountered, they are characteristic of the surface structure. In the human body, the surface structure is viewed as a pass (T cells check the cell surface of other cells to detect whether those cells are foreign to the body ). Problems occur when the surfaces of these cells are altered. In organ transplantation, this aspect is a major problem, because in many cases the transplanted organs are rejected by the body. In kidney and bone marrow transplants is therefore trying to find donor-recipient pairs that go together as far as possible with the surface structures of the organ recipient.
Immune tolerance
The first researcher to "self" and "foreign" recognized the difference between, was the German microbiologist Paul Ehrlich. He originally wanted to find out in 1900, what happens to blood that remains after internal bleeding. Therefore he started an experiment by injecting goats sheep blood. The amazing thing was that the immune system the foreign blood cells ( erythrocytes) destroyed immediately.
When Ehrlich later the experiment with similar types of animals carried out, the same thing happened. The immune system fought against the foreign blood cells.
It was only when he was treating a goat with their own blood, Ehrlich recognized that the body recognizes what is exogenous and endogenous. Goat destroyed in this experiment, the injected blood cells do not (although Ehrlich blood stored for a certain time ). Ehrlich introduced as a result of these experiments, the biological principle of horror autotoxicus ( fear of self-destruction ) on. Although this principle sounds very simple, it is still essential for all living things. Would the goat reduce their own blood, they would even the slightest injury die (if their immune system would attack their own blood ). But this self-protection is not always an advantage. The body's own cancer cells are therefore preserved from destruction. Because the body attacks itself is normally not to themselves. Cancer cells are attacked by the immune system as antigens when they are only clearly enough from non-cancerous cells ( healthy cells ) are different and the immune system is immune competent. That it does occur, that your own body in the case of an autoimmune disease sees his organs as foreign and attacks, is a problem faced by researchers and practitioners.
Formation
The exact cause of autoimmune diseases is still unclear, despite intensive research. Recognized hypotheses assume that autoimmune diseases are acquired through innate " receptivity " (genetic predisposition) in combination with external influences. The genetic predisposition is due primarily to the fact that different people express on the surfaces of their cells, various MHC molecule variants. Depending on the variant is determined individually, which the immune cells (mainly T lymphocytes) are the many fragments of the molecules of a pathogen present, and thus lead to an immune response. Some MHC variants present this exciting ingredients that resemble the body's own structures, and thus trigger an autoreactive immune response. Is it in the body of the person concerned such genetic factors and will be added in addition unfavorable environmental factors, such as severe stress, infection, pregnancy, it can come to the onset of autoimmune diseases. (English Bad luck and bad genes about: , bad luck and bad genes ').
Another theory is the hygiene hypothesis, which deals with the interactions between bacteria and our immune system. Too little discussion of bacteria in the environment, the emergence of immune diseases could be promoted. Another facet of this thesis deals with the composition of the intestinal bacteria and their effect on the immune system. Women are more frequently affected principle of autoimmune diseases and a study in mice suggests that the different composition of the intestinal bacteria of women and men could be a cause for it.
Furthermore, it is assumed that in the selection of T cells during the maturation process in the thymus can escape individual autoreactive T cells of control, if they do not have enough self- antigen are available. This is, for example, the case where the self- antigen in question is not produced in the thymus, is transported there and in sufficient concentration so-called migratory cells.
The target structure of the autoimmune response may be limited to a specific organ (from the hair root to the liver) or the whole body (several organs and vascular system ) affected. Mixed forms with several autoimmune diseases are rare.
Autoantibodies
Meeting for the people above factors ( hereditary susceptibility as well as adverse environmental conditions, such as a viral infection), then creates an auto-immune disease. Autoantigens, such as remnants of cell membranes (as membrane vesicles or micelles), DNA fragments or endogenous proteins float in the bloodstream throughout the body. T lymphocytes and other immune cells now recognize these antigens as foreign incorrectly. As with a natural defense reaction, the immune response turns off after the recognition of a "foreign body " field. Inflammation -promoting substances (certain cytokines) are released and consequently promoted cell-cell communication. More and more immune cells are attracted, and the wrong information to be forwarded. B lymphocytes differentiate into plasma cells and start the production of autoantibodies (auto sensitization) that are released into the blood. With the blood they reach the entire body and bind to their specific antigens. There, the antibodies attach to the targets of the autoimmune response and mark these cells for macrophages and CD8 T cells to be eliminated. This leads to damage of the affected organ. In the same way, these antibodies can dock to nerve cells and such as in multiple sclerosis cause faults that are specific to the region of the brain.
Only due to the loss of immune tolerance, a pathogen can cause the outbreak of an autoimmune disease. This pathogen would have a high similarity with the structure of the body's own tissue have ( many pathogens try the body through its surface to deceive, so that they can enter the body unhindered, this attempt at deception is called molecular mimicry ). After recognizing the pathogen the immune system is fighting this ( auto-antibodies are formed and immune cells attack while also own tissue structures to ). After the initial immune response remain permanent memory cells in the body, the "search" for this pathogen, which could lead to autoimmune disease (specific memory T cells encounter the relevant tissue and cause defensive reactions ). A well-known example is the so-called rheumatic fever, an infection caused by streptococci (specifically β - hemolytic streptococci ). The antibodies are formed against this pathogen, the tissue of the heart muscle can attack if you are genetically prone to autoimmune diseases.
Decisive in each case the amount of existing serological autoantibody titer as a criterion for the diagnosis of autoimmune disease, because autoantibodies are usually physiologically (eg, ANA, dsDNA antibodies and anti -phospholipid antibodies). Exceeding a given titer is considered to be pathological. Some autoantibodies are not physiologically and from the outset as pathologically to be considered (eg, ANCA and Endomysial antibodies) are addition, increased or existing autoantibody titer is not absolutely necessary for the diagnosis of autoimmune disease because an autoimmune disease is made on the basis of serological and clinical criteria. Alone increased or existing pathological autoantibody titer sufficient for a diagnosis of, since these scores based on a ( reaching a certain number of points ) is provided.
Therapy
The causes of autoimmune diseases are known, no causal therapy is possible. Autoimmune diseases can therefore only be treated symptomatically (anti-inflammatory, immunosuppressive, respectively ). Autoimmune diseases are treated, depending on the organs affected by the relevant specialists, such as internists, dermatologists, neurologists, endocrinologists or nuclear medicine. Basic principle of the symptomatic therapy of this is to attenuate the activity of the immune system by administration of immunosuppressants, such as cortisone. Due to the varied systemic side effects and interactions of these substances new drugs are developed specifically affect the mechanisms involved in the disease. Examples include natalizumab and infliximab, which are used for treatment of multiple sclerosis or rheumatoid arthritis. Although these newer agents act specifically and are well tolerated by most patients, it can in rare cases cause serious side effects occur (such as progressive multifocal leukoencephalopathy ( PML) under natalizumab).
Classification
There are hundreds of known autoimmune diseases, of which only about 400 diseases are the " rheumatic form circle " attributed. The spectrum of diseased organs is great. It must be assumed that virtually any organ or tissue can be the target of an autoimmune disease.
One can divide this disease into three groups: