Autoimmune disease

An autoimmune disease, also autoimmune disease, is a disorder caused by the immune system itself, which attacks the body's own cells. In this case, the protective system becomes the aggressor, attacking and destroying the body's own healthy organs and tissues instead of protecting them. An exaggerated immune response is then given against substances and tissues that are normally present in the body.

More than eighty autoimmune diseases have been identified. The most common are celiac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

Classification

• Systemic autoimmune diseases (non-specific organ): occur when antibodies attack non-specific antigens in more than one particular organ. Thus, there is a group of diseases that, despite having some specific antigens of some organs, do not present exclusivity to these, such as polimiositis. The best example for this type of disease is systemic erythematous lupus, which has a greater frequency in women in the middle of their lives.
• Local syndrome (specific oregano): it may be endocrine (diabetes mellitus type 1, Addison disease, Hashimoto thyroiditis, etc.), dermatological (commodular lymphocyte), or hematological (autoimmune hemolytic anemia), and involves a particular tissue.

Organ Specific

Multiorganic or systemic

Etiology

It is generally accepted that the interaction between environmental factors and specific susceptibility genes is responsible for the development of autoimmune diseases. Less than 10% of people with a higher genetic susceptibility develop the disease, suggesting a strong environmental trigger, which also affects disease progression and prognosis. The current theory is that antigens absorbed from the gut may be involved.

Ancient Theories

Shortly after autoimmune diseases were first identified more than a century ago, researchers began to associate them with viral and bacterial infections. This association was explained by a mechanism called "molecular mimicry", based on the close resemblance between antigens (or, more correctly, epitopes) of the microorganisms and autoantigens. This theory postulates that the induction of an immune response against the microbial antigen then provokes a cross-reaction with autoantigens and the appearance of autoimmune processes; once these processes are activated, the autoimmune response becomes independent of continued exposure to the environmental trigger, and consequently the process is self-perpetuating and irreversible.

Another theory suggests that microorganisms expose autoantigens to the immune system through direct tissue damage during active infection. This mechanism has received the name of "bystander effect". The phenomenon by which pathogens mimic self-antigens, release sequestered self-antigens, or both remains to be clarified.

Recently, it has been proposed that increased hygiene and a lack of exposure to various microorganisms are responsible for the epidemic of autoimmune diseases that has been experienced since the 1960s and 1970s. The essence of the "hygiene hypothesis" argues that the increasing incidence of diseases of immune (including autoimmune) origin is due, at least in part, to lifestyle and environmental changes that have made us "too clean." Regardless of whether autoimmune diseases result from too much or too little exposure to microorganisms, adaptive immunity and the imbalance between Th1, Th2, Th17 and regulatory T cell responses are now generally considered to be key elements in the development of autoimmune diseases.

New theories: increased intestinal permeability

Spray of the wall of the intestine with increased permeability. The two most powerful factors that cause it are certain intestinal bacteria and gliadine (main toxic fraction of gluten), regardless of genetic predisposition, i.e., both in celiacs and in non celiacs. This allows the uncontrolled passage of substances to the bloodstream, with the consequent possible development of autoimmune diseases, inflammatory, infections, allergies or cancers, both intestinal and other organs.

The alteration of intestinal permeability is implicated in the development of a growing number of diseases, including autoimmune diseases, in which the increase in intestinal permeability allows the passage of antigens from the intestine into the blood, producing a immune response that can be directed against any organ or tissue, in genetically predisposed individuals.

In most cases, increased intestinal permeability occurs before the disease and causes an abnormality in antigen exposure that triggers the multi-organ process that leads to the development of autoimmune diseases.

A common denominator of autoimmune diseases is the presence of several pre-existing processes that cause an autoimmune response. The first is a genetic susceptibility of the immune system to recognize, and potentially misinterpret, an environmental antigen presented within the digestive tract. Second, there must be an exposure to the antigen. Finally, the antigen must be presented to the immune system, after passing through the intestinal barrier, which is normally blocked when it works properly. The intestinal epithelium is the largest mucosal surface in the body and interacts with the environment. When the intestinal mucosa is healthy, with intact permeability, it constitutes the main barrier to prevent the passage of macromolecules (incompletely digested nutrients and certain intestinal bacteria). When intestinal permeability is damaged (increased), the intestinal barrier loses its protective function and molecules that should not pass enter the bloodstream, causing immune reactions.

Another critical factor for intestinal immune responsiveness is the major histocompatibility complex. The HLA class I and II genes code for peptide-binding glycoproteins, and this HLA-peptide complex is recognized by certain T-lymphocyte receptors in the intestinal mucosa. Susceptibility to developing at least 50 diseases has been associated with specific HLA class I or II alleles.

The two most potent factors that cause increased intestinal permeability are certain intestinal bacteria and gliadin (the main toxic fraction of gluten), regardless of genetic predisposition, that is, both in celiac and non-celiac patients. Other possible causes are prematurity, radiation exposure, and chemotherapy.

The following hypothesis summarizes the three key points that explain the pathogenesis of autoimmune diseases:

1. Autoimmune diseases involve miscommunication between innate immunity and acquired immunity.
2. Molecular or transient imitation effects cannot alone explain the complex mechanisms involved in the emergence of autoimmune diseases. Rather, in order to perpetuate the disease process, continuous stimulation appears to be necessary through non-inclusive antigens (environmental decayants). This implies that the autoimmune response can be in arrested and possibly inverted theory, if the environmental trigger or trigger is eliminated.
3. In addition to a genetic predisposition and exposure to the triggering environmental factor, the third key element necessary to develop self-immunity is the loss of the protective function of mucous barriers, mainly the intestinal barrier and pulmonary mucosa, which create an area of interaction with the environment.

Forecast

New theories about the causes that cause the development of autoimmune diseases imply that after the autoimmune process has been activated, it does not perpetuate itself, but can be modulated, or even stopped, avoiding the continuous interaction between genes and environment through removal of the triggering environmental factor(s). There is also a correlation between the emergence of modern medicine with the increase in autoimmune diseases, since in the past the presence of this type of disease was rare. However, this does not imply causation.