Autoimmune disease

Autoimmune disease in medicine is an umbrella term for diseases which cause an excessive reaction of the immune system against the body’s own tissues.

The immune system mistakenly recognizes the body’s own tissue as foreign objects to be controlled. This leads to severe inflammatory reactions that lead to damage of the affected organs.

Definition

The immune system is responsible for the detection and defense against foreign substances, micro organisms and viruses, playing an important role for T-cells, which are trained in the thymus to their own MHC molecules and tolerate the body’s own structures.

This process is known as “clonal deletion”. In the positive selection in the thymus, only those T cells can recognize MHC molecules on the body’s cell membranes.

T cells, their own MHC molecules cannot detect binding (i.e. are eliminated). When also taking place in the thymus, negative selection eliminates those T-cells and the body’s own MHC molecules bind so tightly that they are activated – which would ultimately lead to the destruction of the body’s own cells.

This central immune tolerance is one of the measures taken by the immune system to “protect” itself and “to combat aliens”.

Autoimmune diseases behave like a group of T cells. Cells of the immune system now recognize the body’s own structures as foreign. The immune system directs its defense (cellular as well as humoral defense reactions, are formed into auto antibodies) against the body’s own tissue during repair mechanisms of the body to try wherever possible to renew damaged body parts.

This mistaken attack by the immune system continues without treatment, usually for life or until the complete destruction of the target structure.

MHC molecules

Our bodies may be between their own and exogenous protein molecules (such as disposal of bacteria, viruses or worms differ). Crucial for the distinction is the MHC proteins complex.

With the help of these membrane proteins, the immune system recognizes “self” cells. There are two types of MHC proteins, proteins of class I (HLA Class I molecules) are found on all nucleated cells of the body. MHC molecules of class II (HLA class II molecules) are however only on the surface of antigen-presenting cells (such as in macrophages).

The class I and II MHC molecules are encoded by 13 or 14 genes, with the exception of β2-microglobulin which are all located in the HLA locus on chromosome 6.

These genes are polymorphic, meaning that they exist at the population level and have a large number of different alleles. Therefore two widely related people rarely have the same set of MHC proteins.

MHC proteins on the surface of almost all cells (red cells found), are characteristic of the surface structure. In the human body, the surface structure is regarded as proof of identity (T-cells, the cell surfaces of other cells to see whether these cells are a foreign body). Problems occur when the surfaces of these cells are altered.

In organ transplantation, this aspect is a big problem, because in many cases the transplanted organ is rejected by the body. In kidney and bone marrow transplants therefore they seek to find donor-recipient pairs, that come together largely with the surface structures of the organ recipient.

Immune tolerance

The first scientist to recognize the difference between “self” and “alien” was the German microbiologist Paul Ehrlich. He wanted to find out originally in 1900, what happens to blood remaining after internal bleeding.

So he started an experiment by injecting goats with sheep blood. The amazing thing was that the immune system immediately destroyed the foreign blood cells (erythrocytes). As Ehrlich later conducted the experiment with similar types of animals, the same thing happened.

The immune system fought back against the foreign blood cells. Only when he treated a goat with her own blood, Ehrlich acknowledged that the body recognized what was a foreign body with it’s physical self.

Ehrlich introduced as a result of these experiments, the biological principle of Horror autotoxicus (fear before self-destruction). Although this principle sounds very simple, it is nevertheless vital for all living beings.

The goat would reduce their own blood, even the slightest injury it would die if it’s immune system would attack its own blood. The body’s own cancer cells are thus saved from its destruction. In today’s medicine has has been discovered lately, that cancer cells such as antigens are attacked by the immune system if it is just clear enough to distinguish by non-cancer cells (normal cells).

Genesis

The exact cause of autoimmune diseases is still unclear, despite intensive research. Recognized hypotheses assume that autoimmune diseases are acquired through innate susceptibility (genetic predisposition) in combination with external influences.

The genetic predisposition is attributable primarily to the fact that different people express on the surfaces of their cells, different variants of MHC molecules. Depending on the variant it will be individually determined with many fragments of the molecules of a pathogen of the immune cells (primarily T lymphocytes) and thus lead to an immune response.

Some MHC variants present this pathogen component. The body’s structures are similar, and thus trigger an auto-reactive immune response.

Such genetic factors are also unfavorable environmental factors such as high stress, infections and pregnancy. In addition, one assumes that they may go unnoticed in the selection of T cells during the process of maturation in the thymus.

The targets of the autoimmune response may be limited to a specific organ (of the hair root to the liver) or the whole body (several organs and vascular system) is overcome. Mixed forms with multiple autoimmune diseases are not uncommon.

Autoantibodies

Autoantigens, such as remnants of cell membranes (a membrane vesicles or micelles), DNA fragments or blood proteins float in the bloodstream throughout the body. T-lymphocytes and other immune cells then mistakenly identify these antigens as foreign.

As with a natural defense mechanism it, after the detection of a “foreign body” gives the immune a response. Inflammatory substances (certain cytokines are released) promote cell-cell communication. More and more immune cells are attracted, and the wrong information will be forwarded.

B lymphocytes differentiate into plasma cells and start the production of auto-antibodies (auto sensitization) that are released into the blood. With the blood they get into the body and bind to their specific antigens (such as cell walls). There, the antibodies attach themselves to the target structures of autoimmunity and mark these cells for macrophages and CD8 T cells that can be eliminated.

This leads to damage of the affected organ. In the same way, these antibodies can attach themselves to nerve cells and cause such disruption such as multiple sclerosis, which is specific to the brain region. Besides the factor of the loss of immune tolerance, a pathogen could cause the outbreak of an autoimmune disease.

However, that agent should have a high similarity to the structure of the body’s own tissue (many agents are trying to deceive the body through its surface, so that they can freely enter the body at deception called molecular mimicry). After identifying the pathogen, the immune system will fight them (autoantibodies are formed, and thereby immune cells attack their own tissue structures).

Remaining permanently after the initial immune response, memory cells in the body look for this pathogen, which leads to autoimmune disease (specific memory cells encounter the relevant tissue and cause defensive reactions).

A familiar example is the so-called rheumatic fever, an infection by streptococci (specifically β-hemolytic streptococci). The antibodies are formed against this pathogen may attack the tissues of the heart muscle, if you are genetically prone to autoimmune diseases.

Some auto antibodies are considered not physiologically and pathologically from the outset as (for example, ANCA and endomysial antibodies also) increasing and are not necessary for the diagnosis of autoimmune disease based on serological and clinical criteria.

Therapy

Because the causes of autoimmune diseases are unknown, it is no causal therapy. Autoimmune diseases can therefore only be treated symptomatically (anti-inflammatory, or immunosuppressive). Autoimmune diseases are treated depending on the organ by the relevant specialists, including internists, dermatologists, neurologists, endocrinologists and nuclear medicine.

Basic principles of symptomatic therapy is to dampen the activity of the immune system by administration of immunosuppressive drugs such as cortisone. Because of the varied systemic side effects and interactions of these substances they have been trying to develop new drugs that specifically affect the mechanisms involved in the disease process.

Examples include natalizumab and infliximab, which are used for the treatment of multiple sclerosis or rheumatoid arthritis. Although these newer agents are specifically effective and well tolerated by most patients, it may, in rare cases, cause serious side effects.