Autoimmune diseases: what are they? Autoimmune diseases: pathogenesis, clinical syndromes, laboratory immunodiagnostic methods. Treatment Principles Are Chronic Fatigue Syndrome and Fibromyalgia Autoimmune Diseases?

6.1 AUTOIMMUNE DISEASES

Autoimmune diseases are quite widespread in the human population: they affect up to 5% of the world's population. For example, 6.5 million people in the United States suffer from rheumatoid arthritis; in large cities in England, up to 1% of adults are disabled with multiple sclerosis; juvenile diabetes affects up to 0.5% of the world's population. The sad examples can be continued.

First of all, it should be noted the difference between autoimmune reactions, or autoimmune syndrome And autoimmune diseases, which are based on the interaction between the components of the immune system and one’s own healthy cells and tissues. The former develop in a healthy body, proceed continuously and eliminate dying, aging, diseased cells, and also arise in any pathology, where they act not as its cause, but as a consequence. Autoimmune diseases, of which there are currently about 80, are characterized by a self-sustaining immune response to the body’s own antigens, which damages cells containing self-antigens. Often the development of an autoimmune syndrome further develops into an autoimmune disease.

Classification of autoimmune diseases

Autoimmune diseases are conventionally divided into three main types.

1. Organ-specific diseases, which are caused by autoantibodies and sensitized lymphocytes against one or a group of autoantigens of a specific organ. Most often, these are barrier antigens to which there is no natural (innate) tolerance. These include Hoshimoto's thyroiditis, myasthenia gravis, primary myxedema (thyrotoxicosis), pernicious anemia, autoimmune atrophic gastritis, Addison's disease, early menopause, male infertility, pemphigus vulgaris, sympathetic ophthalmia, autoimmune myocarditis and uveitis.

2. For non-organ-specific diseases autoantibodies to autoantigens of cell nuclei, cytoplasmic enzymes, mitochondria, etc. interact with different tissues of a given or even another

type of organism. In this case, autoantigens are not isolated (are not “barrier”) from contact with lymphoid cells. Autoimmunization develops against the background of pre-existing tolerance. Such pathological processes include systemic lupus erythematosus, discoid erythematous lupus, rheumatoid arthritis, dermatomyositis (scleroderma).

3. Mixed diseases involve both of these mechanisms. If the role of autoantibodies is proven, then they should be cytotoxic against the cells of the affected organs (or act directly through the AG-AT complex), which, when deposited in the body, cause its pathology. These diseases include primary biliary cirrhosis, Sjogren's syndrome, ulcerative colitis, celiac enteropathy, Goodpasture's syndrome, type 1 diabetes mellitus, and an autoimmune form of bronchial asthma.

Mechanisms of development of autoimmune reactions

One of the main mechanisms that prevents the development of autoimmune aggression in the body against its own tissues is the formation of unresponsiveness to them, called immunological tolerance. It is not congenital, it is formed in the embryonic period and consists of negative selection, those. elimination of autoreactive cell clones that carry autoantigens on their surface. It is the violation of such tolerance that is accompanied by the development of autoimmune aggression and, as a consequence, the formation of autoimmunity. As Burnet noted in his theory, during the embryonic period, contact of such autoreactive clones with “their” antigen causes not activation, but cell death.

However, not all so simple.

Firstly, it is important to say that the antigen recognition repertoire located on T lymphocytes preserves all clones of cells carrying all types of receptors for all possible antigens, including autoantigens, on which they are complexed together with their own HLA molecules, which makes it possible to distinguish “own” and “foreign” cells. This is the stage of "positive selection" followed by negative selection autoreactive clones. They begin to interact with dendritic cells carrying the same complexes of HLA molecules with thymic autoantigens. This interaction is accompanied by signal transmission to autoreactive thymocytes, and they undergo death through the mechanism of apoptosis. However, not all autoantigens are present in the thymus, so some

autoreactive T cells are still not eliminated and move from the thymus to the periphery. They are the ones who provide the autoimmune “noise.” However, as a rule, these cells have reduced functional activity and do not cause pathological reactions, just like autoreactive B lymphocytes, which are subject to negative selection and escape elimination, also cannot cause a full autoimmune response, since they do not receive a costimulatory signal from T helper cells, and in addition, they can be suppressed by special suppressor drugs veto -cells.

Secondly, despite negative selection in the thymus, some autoreactive lymphocyte clones still survive due to the imperfection of the elimination system and the presence of long-term memory cells, circulate in the body for a long time and cause the subsequent development of autoimmune aggression.

After the creation of Erne's new theory in the 70s of the last century, the mechanisms of development of autoimmune aggression became even more clear. It was assumed that the body constantly operates a system self-control including the presence on lymphocytes of receptors for antigens and special receptors for these receptors. Such antigen-recognizing receptors and antibodies to antigens (which are also actually their soluble receptors) were called idiots, and the corresponding antireceptors, or antiantibodies - anti-idiotypes.

Currently the balance between idiotype-antiidiotype interactions is considered as the most important self-recognition system, which is a key process in maintaining cellular homeostasis in the body. Naturally, a violation of this balance is accompanied by the development of autoimmune pathology.

Such a disorder may be caused by: (1) a decrease in the suppressor activity of cells, (2) the appearance in the bloodstream of barrier (“sequestered” antigens of the eye, gonads, brain, cranial nerves, with which the immune system normally does not have contact and when it occurs reacts to them as foreign, (3) antigenic mimicry due to microbial antigens that have common determinants with normal antigens, (4) mutation of autoantigens, accompanied by modification of their specificity, (5) increase in the number of autoantigens in circulation, (6) modification of autoantigens by chemical agents, viruses, etc. with the formation of biologically highly active superantigens.

The key cell of the immune system in the development of autoimmune diseases is the autoreactive T-lymphocyte, which reacts to a specific autoantigen in organ-specific diseases and then, through the immune cascade and the involvement of B-lymphocytes, causes the formation of organ-specific autoantibodies. In the case of organ-nonspecific diseases, most likely, autoreactive T lymphocytes interact not with the epitope of the autoantigen, but with the antigenic determinant of anti-idiotypic autoantibodies to it, as indicated above. Moreover, autoreactive B lymphocytes, which cannot be activated in the absence of a T cell costimulatory factor and synthesize autoantibodies, themselves have the ability to present a mimic antigen without an Ag-presenting cell and present it to non-autoreactive T lymphocytes, which turn into T helper cells and activate B cells for the synthesis of autoantibodies.

Among the autoantibodies produced by B lymphocytes, the following are of particular interest: natural autoantibodies to autologous antigens, which in a significant percentage of cases are detected and persist for a long time in healthy people. As a rule, these are autoantibodies of the IgM class, which, apparently, should still be considered precursors of autoimmune pathology. For this reason, in order to understand the detailed situation and establish the pathogenic role of autoantibodies, the following criteria for diagnosing autoaggression are proposed:

1. Direct evidence of circulating or associated autoAbs or sensitized Lf directed against autoAgs associated with the disease.

2. Identification of the causative autoAG against which the immune response is directed.

3. Adoptive transfer of the autoimmune process by serum or sensitized Lf.

4. The possibility of creating an experimental model of the disease with morphological changes and the synthesis of AT or sensitized Lf when modeling the disease.

Be that as it may, specific autoantibodies serve as markers of autoimmune diseases and are used in their diagnosis.

It should be noted that the presence of specific autoantibodies and sensitized cells is not yet sufficient for the development of an autoimmune disease. A major role is played by pathogenic environmental factors (radiation, force fields, polluted

products, microorganisms and viruses, etc.), genetic predisposition of the body, including those linked to HLA genes (multiple sclerosis, diabetes, etc.), hormonal levels, use of various medications, immune disorders, including cytokine balance.

At present, a number of hypotheses for the mechanism of induction of autoimmune reactions can be proposed (the information given below is partially borrowed from R.V. Petrov).

1. Despite the self-control system, the body contains autoreactive T- and B-lymphocytes, which, under certain conditions, interact with antigens of normal tissues, destroy them, promoting the release of hidden autoantigens, stimulants, mitogens that activate cells, including B-lymphocytes.

2. For injuries, infections, degenerations, inflammation, etc. “sequestered” (barrier) autoantigens are released, to which autoantibodies are produced that destroy organs and tissues.

3. Cross-reacting “mimicking” antigens of microorganisms, common with autoantigens of normal tissues. Staying in the body for a long time, they eliminate tolerance and activate B cells to synthesize aggressive autoantibodies: for example, group A hemolytic streptococcus and rheumatic disease of the heart valves and joints.

4. “Superantigens” - toxic proteins formed by cocci and retroviruses that cause strong activation of lymphocytes. For example, normal antigens activate only 1 in 10,000 T cells, and superantigens activate 4 out of 5! The autoreactive lymphocytes present in the body will immediately trigger autoimmune reactions.

5. The presence in patients of a genetically programmed weakness of the immune response to a specific antigen immunodeficiency. If it is contained by a microorganism, a chronic infection occurs, destroying tissue and releasing various autoags, to which an autoimmune response develops.

6. Congenital deficiency of T-suppressor cells, which abolishes the control of B-cell function and induces their response to normal antigens with all the consequences.

7. Autoantibodies under certain conditions “blind” Lf, blocking their receptors that recognize “self” and “foreign”. As a result, natural tolerance is canceled and an autoimmune process is formed.

In addition to the above mechanisms of induction of autoimmune reactions, it should also be noted:

1. Induction of the expression of HLA-DR antigens on cells that previously did not have them.

2. Induction by viruses and other agents of modification of the activity of autoantigens-oncogenes, regulators of cytokine production and their receptors.

3. Reduced apoptosis of T-helper cells that activate B-lymphocytes. Moreover, in the absence of a proliferative stimulus, B lymphocytes die from apoptosis, whereas in autoimmune diseases it is suppressed and such cells, on the contrary, accumulate in the body.

4. Mutation of the Fas ligand, which leads to the fact that its interaction with the Fas receptor does not induce apoptosis in autoreactive T cells, but suppresses the binding of the receptor to the soluble Fas ligand and thereby delays the cell apoptosis induced by it.

5. Deficiency of special T-regulatory CD4+CD25+ T-lymphocytes with FoxP3 gene expression, which block the proliferation of autoreactive T-lymphocytes, which significantly enhances it.

6. Disruption of the binding site on chromosomes 2 and 17 of the special regulatory protein Runx-1 (RA, SLE, psoriasis).

7. Formation in the fetus of autoantibodies of the IgM class to many components of autocells, which are not eliminated from the body, accumulate with age and cause autoimmune diseases in adults.

8. Immune drugs, vaccines, immunoglobulins can cause autoimmune disorders (dopegite - hemolytic anemia, apressin - SLE, sulfonamides - periarteritis nodosa, pyrazolone and its derivatives - agranulocytosis).

A number of drugs can, if not induce, then intensify the onset of immunopathology.

It is very important for physicians to know that the following drugs have immunostimulating potencies: antibiotics(Eric, amphotericin B, levorin, nystatin),nitrofurans(furazolidone),antiseptics(chlorophyllipt),metabolism stimulants(orotate K, riboxin),psychotropic drugs(nootropil, piracetam, phenamine, sydnocarb),plasma replacement solutions(hemodez, rheopolyglucin, gelatinol).

The association of autoimmune diseases with other diseases

Autoimmune disorders (rheumatic diseases) may be accompanied by tumor lesions of lymphoid tissue and neoplastic

lasers of other localizations, but patients with lymphoproliferative diseases often exhibit symptoms of autoimmune conditions (Table 1).

Table 1. Rheumatic autoimmune pathology in malignant neoplasms

Thus, with hypertrophic osteoarthropathy, cancer of the lungs, pleura, diaphragm, and less often of the gastrointestinal tract is detected, with secondary gout - lymphoproliferative tumors and metastases, with pyrophosphate arthropathy and monoarthritis - bone metastases. Often polyarthritis and lupus-like and scleral-like syndromes are accompanied by malignant tumors of various localizations, and polymyalgia rheumatica and cryoglobulinemia are accompanied, respectively, by cancer of the lungs, bronchi and hyperviscosity syndrome.

Often malignant neoplasms are manifested by rheumatic diseases (Table 2).

With rheumatoid arthritis, the risk of developing lymphogranulomatosis, chronic myeloid leukemia, and myeloma is increased. Tumors more often occur during the chronic course of the disease. The induction of neoplasms increases with the duration of the disease, for example, in Sjögren's syndrome, the risk of cancer increases by 40 times.

These processes are based on the following mechanisms: expression of the CD5 antigen on B cells that synthesize organ-specific antibodies (normally this antigen is presented on T lymphocytes); excessive proliferation of large granular lymphocytes, having

Table 2. Malignant tumors and rheumatic diseases

those with the activity of natural killer cells (phenotypically they belong to CD8 + lymphocytes); infection with retroviruses HTLV-1 and Epstein-Barr viruses; polyclonal activation of B cells with loss of regulation of this process; hyperproduction of IL-6; long-term treatment with cytostatics; disruption of natural killer cell activity; deficiency of CD4+ lymphocytes.

In primary immunodeficiencies, signs of autoimmune processes are often found. A high frequency of autoimmune disorders has been identified in sex-linked hypogammaglobulinemia, IgA deficiency, immunodeficiency with overproduction of IgA, ataxia-telangiectasia, thymoma, and Wiskott-Aldrich syndrome.

On the other hand, there are a number of autoimmune diseases in which immunodeficiencies have been identified (primarily related to T-cell function). In persons with systemic diseases, this phenomenon is expressed more often (with SLE in 50-90% of cases) than with organ-specific diseases (with thyroiditis in 20-40% of cases).

Autoantibodies occur more often in older people. This applies to the determination of rheumatoid and antinuclear factors, as well as antibodies detected in the Wasserman reaction. In asymptomatic 70-year-olds, autoantibodies against various tissues and cells are detected in at least 60% of cases.

What is common in the clinical picture of autoimmune diseases is their duration. There are chronic progressive or chronically relapsing course of pathological processes. Information about the features of the clinical expression of individual autoimmune diseases is presented below (partial information provided is borrowed from S.V. Suchkov).

Characteristics of some autoimmune diseases

Systemic lupus erythematosus

An autoimmune disease with systemic damage to connective tissue, with collagen deposition and the formation of vasculitis. It is characterized by polysymptoms and usually develops in young people. Almost all organs and many joints are involved in the process, and kidney damage is fatal.

With this pathology, antinuclear autoantibodies are formed to DNA, including native DNA, nucleoproteins, cytoplasmic and cytoskeletal antigens, and microbial proteins. It is believed that autoAbs to DNA appear as a result of the formation of its immunogenic form in complex with a protein, or an IgM autoantibody of anti-DNA specificity, which arose in the embryonic period, or the interaction of idiotype-antiidiotype and cell components during microbial or viral infection. Perhaps a certain role belongs to cell apoptosis, which in SLE causes, under the influence of caspase 3, the cleavage of the nucleoproteasome complex of the nucleus with the formation of a number of products that react with the corresponding autoantibodies. Indeed, the content of nucleosomes is sharply increased in the blood of patients with SLE. Moreover, autoantibodies to native DNA are the most diagnostically significant.

An extremely interesting observation is the discovery that DNA-binding autoantibodies also have the enzymatic ability to hydrolyze a DNA molecule without complement. This antibody was called a DNA abzyme. There is no doubt that this fundamental pattern, which, as it turns out, is realized not only in SLE, plays a huge role in the pathogenesis of autoimmune diseases. In this model, the anti-DNA autoantibody has cytotoxic activity towards the cell, which is realized by two mechanisms: receptor-mediated apoptosis and DNA abzyme catalysis.

Rheumatoid arthritis

Autoantibodies are formed against extracellular components that cause chronic inflammation of the joints. Autoantibodies belong mainly to the IgM class, although IgG, IgA and IgE are also found, are formed against the Fc fragments of immunoglobulin G and are called rheumatoid factor (RF). In addition to them, autoantibodies are synthesized to keratohyalin grains (antiperinuclear factor), keratin (antikeratin antibodies), and collagen. It is significant that autoantibodies to collagen are nonspecific, while antiperinuclear factor may be a precursor to the formation of RA. It should also be noted that the detection of IgM-RF allows one to classify seropositive or seronegative RA, and IgA-RF turns out to be a criterion for a highly active process.

In the synovial fluid of the joints, autoreactive T-lymphocytes were found that cause inflammation, which involves macrophages, which enhance it with proinflammatory cytokines, followed by the formation of synovial hyperplasia and cartilage damage. These facts have led to the emergence of a hypothesis that allows the initiation of the autoimmune process by T-helper type 1 cells, activated by an unknown epitope with a costimulatory molecule, which destroy the joint.

Hoshimoto's autoimmune thyroiditis

A disease of the thyroid gland, accompanied by its functional inferiority with aseptic inflammation of the parenchyma, which is often infiltrated by lymphocytes and is subsequently replaced by connective tissue, forming seals in the gland. This disease manifests itself in three forms - Hoshimoto's thyroiditis, primary myxedema and thyrotoxicosis, or Graves' disease. The first two forms are characterized by hypothyroidism, the autoantigen in the first case is thyroglobulin, and in myxedema - proteins of the cell surface and cytoplasm. In general, autoantibodies to thyroglobulin, thyroid-stimulating hormone receptor and thyroid peroxidase have a key influence on the function of the thyroid gland; they are also used in the diagnosis of pathology. Autoantibodies suppress the synthesis of hormones by the thyroid gland, which affects its function. At the same time, B lymphocytes can bind to autoantigens (epitopes), thereby influencing the proliferation of both types of T helper cells, which is accompanied by the development of an autoimmune disease.

Autoimmune myocarditis

In this disease, the key role is played by a viral infection, which is most likely its trigger. It is with this that the role of mimicking antigens is most clearly seen.

In patients with this pathology, autoantibodies to cardiomyosin, receptors of the outer membrane of myocytes and, most importantly, to proteins of Coxsackie viruses and cytomegaloviruses are detected. It is significant that during these infections a very high viremia is detected in the blood; viral antigens in a processed form accumulate on professional antigen-presenting cells, which can activate unprimed clones of autoreactive T-lymphocytes. The latter begin to interact with non-professional antigen-presenting cells, because do not require a costimulatory signal, and interact with myocardial cells, on which, due to activation by antigens, the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) sharply increases. The process of interaction between autoreactive T lymphocytes is also sharply enhanced and facilitated by increased expression of HLA class II molecules on cardiomyocytes. Those. autoantigens of myocardiocytes are recognized by T helper cells. The development of an autoimmune process and viral infection behaves very typically: initially, powerful viremia and high titers of antiviral autoantibodies, then a decrease in viremia down to virus negativity and antiviral antibodies, an increase in antimyocardial autoantibodies with the development of autoimmune heart disease. The experiments clearly demonstrated the autoimmune mechanism of the process, in which the transfer of T lymphocytes from infected mice with myocarditis induced disease in healthy animals. On the other hand, T cell suppression was accompanied by a dramatic positive therapeutic effect.

Myasthenia gravis

In this disease, a key role is played by autoantibodies to acetylcholine receptors, which block their interaction with acetylcholine, completely suppressing the function of the receptors or sharply enhancing it. The consequence of such processes is a disruption in the transmission of nerve impulses up to severe muscle weakness and even respiratory arrest.

A significant role in the pathology belongs to T-lymphocytes and disturbances in the idiotypic network; there is also a sharp hypertrophy of the thymus with the development of thymoma.

Autoimmune uveitis

As in the case of myasthenia gravis, infection with protozoa plays a significant role in the development of autoimmune uveitis, in which autoimmune chronic inflammation of the uvearetinal tract develops Toxoplasma gondii and cytomegaly and herpes simplex viruses. In this case, a key role belongs to mimicking antigens of pathogens that have common determinants with eye tissues. With this disease, autoantibodies appear to autoantigens of the eye tissue and microbial proteins. This pathology is truly autoimmune, since the introduction of five purified eye antigens to experimental animals causes them to develop classical autoimmune uveitis due to the formation of corresponding autoantibodies and damage to the uveal membrane.

Insulin-dependent diabetes mellitus

A widespread autoimmune disease in which immune autoaggression is directed against the autoantigens of the cells of the islets of Langerhans; they are destroyed, which is accompanied by suppression of insulin synthesis and subsequent profound metabolic changes in the body. This disease is mediated mainly by the functioning of cytotoxic T lymphocytes, which are sensitized, apparently, to intracellular glutamic acid decarboxylase and p40 protein. In this pathology, autoantibodies to insulin are also detected, but their pathogenetic role is not yet clear.

Some researchers propose to consider autoimmune reactions in diabetes from three positions: (1) diabetes is a typical autoimmune disease with autoaggression against beta cell autoantigens; (2) in diabetes, the formation of anti-insulin autoantibodies is secondary, forming the syndrome of autoimmune insulin resistance; (3) with diabetes, other immunopathological processes develop, such as the appearance of autoantibodies to the tissues of the eye, kidneys, etc. and their respective lesions.

Crohn's disease

Otherwise, granulomatous colitis is a severe recurrent autoimmune inflammatory disease mainly of the colon

with segmental damage to the entire intestinal wall by lymphocytic granulomas with subsequent formation of penetrating slit-like ulcers. The disease occurs with a frequency of 1:4000, young women are more often affected. It is associated with the HLA-B27 antigen and is caused by the formation of autoantibodies to the tissues of the intestinal mucosa with a decrease in the number and functional activity of suppressor T-lymphocytes and to mimicking microbial antigens. An increased number of IgG-containing lymphocytes specific to tuberculosis was found in the colon. In recent years, there have been encouraging reports of successful treatment of this disease using anti-TNF-β antibodies, which suppress the activity of autoreactive T lymphocytes.

Multiple sclerosis

In this pathology, autoreactive T cells also play a key role with the participation of type 1 T helper cells, which cause the destruction of the myelin sheath of the nerves with the subsequent development of severe symptoms. The target autoantigen is most likely myelin basic protein, to which sensitized T cells are formed. A significant role in pathology belongs to apoptosis, the manifestations of which can determine different types of the process - progressive or remitting. In an experimental model (experimental encephalomyelitis) it is reproduced when animals are immunized with myelin basic protein. A certain role of viral infection in the etiology of multiple sclerosis cannot be ruled out.

Autoimmune diseases of the blood system

There are several of them - autoimmune hemolytic anemia and neutropenia, thrombocytopenic purpura. Caused by the formation of autoantibodies to blood cells. Anemia occurs when anti-erythrocyte IgG autoantibodies cause extravascular lysis of red blood cells with the participation of K cells, which include macrophages and natural killer cells, which fix autoantibodies through the receptor for the Fc fragment of IgG adsorbed on red blood cells. IgM class (cold) autoantibodies lyse red blood cells when body temperature drops to 30 0 C. Neutropenia is caused by the destruction of granulocytes by specific antigranulocyte autoantibodies, thrombocytopenia by antiplatelet autoantibodies. Pernicious anemia is a disease characterized by impaired erythropoiesis, development

tion of hemoblastic type of hematopoiesis, erythrophagia, anemia. Pernicious anemia is often preceded by atrophic gastritis. The pathological process is based on the formation of autoantibodies against gastric parietal cells and intrinsic Castle factor.

Addison's disease

Manifests itself in hormonal insufficiency of the adrenal cortex with a chronic course. Characteristics are hypotension, adynamia, a drop in blood sugar levels, and 17-OX in the urine. Autoantibodies against mitochondria and microsomes of gland cells are detected in the blood serum, which cause atrophy and destruction of the adrenal glands.

Celiac disease (celiac disease, celiac enteropathy)

A chronic disease of the small intestine, which is based on a defect in the mucous membrane in the formation of peptidases that break down plant protein gluten-clecivin contained in cereals. Women are more often affected. Clinically, the disease manifests itself as enteritis, especially when eating foods rich in gluten. Patients often exhibit antibodies to gluten and IgA deficiency.

Goodpasture's syndrome

Systemic capillaritis with predominant damage to the lungs and kidneys, such as hemorrhagic pneumonitis and glomerulonephritis. Men aged 20-30 years are more likely to get sick. There is a definite connection between the disease and viral and bacterial infections and hypothermia. It begins acutely with high fever, wheezing in the lungs, with rapid progression of glomerulonephritis resulting in renal failure. Characterized by hemoptysis, hematuria, anemia. Autoantibodies to the basement membranes of the kidneys are detected, which also react with the basement membranes of the lungs.

Sjögren's syndrome

Chronic inflammation of the exocrine glands (salivary, lacrimal) with lymphoid infiltration followed by atrophy can be combined with dry keratoconjunctivitis, glossitis, dental caries, drug intolerance, pain and swelling of the joints. The gland tissue is affected due to autosensitization and the appearance of immune complexes. The disease most often affects men aged 20-30 years.

Whipple's disease (intestinal lipodystrophy)

A chronic disease with damage to the small intestine with the development of dyspepsia, polyarthritis, less often - damage to the heart valves, polyserositis, lymphadenopathy, diffuse skin pigmentation.

Nonspecific ulcerative colitis

A disease that develops as diffuse chronic inflammation of the intestinal mucosa with the formation of extensive shallow ulcers. With this pathology, the formation of autoantibodies against the mucous membrane of the colon is observed. In 50-80% of patients, antibodies to cytoplasmic antigens of neutrophils are detected, and in the lymphoid-plasma cell infiltrate of the mucous and submucosal colon, 40-50% of cells synthesizing IgG are detected among immunoglobulin-containing cells (normally about 5-10%). Recently, increased numbers of lymphocytes expressing receptors for Mycobacterium paratuberculosis have been detected in the colon and blood.

Behçet's disease

Chronic pathological process with periodic exacerbations. The disease is characterized by the following triad of symptoms: damage to the mucous membrane of the mouth (stomatitis), the mucous membrane of the eyes (conjunctivitis), the uvea of ​​the eyes (uveitis), and the genitals. Patients develop aphthae, ulcers with scarring. Antibodies are detected in the blood that react with the epithelium of the oral mucosa.

Diagnosis of autoimmune diseases

The general principle for diagnosing autoimmune diseases is the detection of autoantibodies or sensitized lymphocytes, but the situation is complicated by the fact that the presence of these factors can be observed in healthy individuals and in patients with an autoimmune process without clinical manifestations.

The main diagnostic criteria, based on evidence of the autoimmune nature of the diseases, have already been discussed above. They are, of course, correct, but it is quite difficult to reproduce them in the daily work of the laboratory. Therefore, no matter how we feel about autoimmunity, autoantibodies certainly serve as markers of autoimmune diseases (Table 3).

Table 3. Types of autoantibodies and their main diagnostic value for various diseases

In addition to the analysis of autoantibodies, it is reported that the determination of ESR and C3 and C4 complement components is sufficiently informative for assessing the stage of the autoimmune disease (exacerbation or remission), its activity and the effectiveness of treatment. Determination of complement components, specifically C3 and C4, allows us to judge the effectiveness of treatment of many autoimmune diseases, for example, they are reduced in SLE with kidney damage, central nervous system damage and hemolytic anemia. Identification of factors Ba, C3, C4a is used in the analysis of the course of RA, SLE, and systemic scleroderma.

RF appears in 75% of patients with RA, Sjogren's syndrome, and systemic vasculitis. It is important that the determination of RF in synovial fluid makes it possible to diagnose seronegative RA. For RA, a very sensitive test for determining autoAb IgG is also used. to citrullinated peptide, which is detected in 78-88% of RA patients with a specificity of 95%.

When diagnosing SLE, the detection of LE cells - Nf or Mn with basophilic inclusions (phagocytosis of the nuclei of destroyed cells coated with antinuclear antibodies [ANA]) was previously used. Nowadays this method is practically not used, because it is labor intensive and not sensitive enough. They use ANA analysis, which appears in 95% of patients within 3 months after the onset of the disease. They are found not only in SLE, but with the use of certain medications and a number of arthritis (mainly in older people).

Analysis of ANA on cell substrates using fluorescent anti-IgG allows one to make a fairly accurate diagnosis of pathology based on the nature of the coloring of cells and their nuclei. For example, diffuse staining (uniform distribution of the label) is the least specific; it occurs more often in SLE, drug-induced lupus syndrome and other autoimmune diseases; in the elderly, it is most likely an autoAb to DNP; peripheral staining - with transformation

harmonization in the serum of anti-DNA autoAT, with lupus nephritis; spotty staining reveals autoATs to extractable nuclear antigens, observed in systemic scleroderma, mixed connective tissue disease, Sjögren's syndrome, drug-induced lupus syndrome; nucleolar staining (label in the nucleoli) autoAb to RNP - systemic scleroderma, some other autoimmune diseases.

Some help in the diagnosis of SLE, periarteritis nodosa, Sjögren's syndrome and Kawasaki disease is also the determination of mixed cryoglobulins-RF and polyclonal autoAbs that reversibly precipitate when<37 0 С.

Since HRT takes part in the formation of autoimmune pathology, in some diseases, in the presence of causative antigens, suppression of leukocyte migration is observed, which has a certain diagnostic value.

Treatment of autoimmune diseases

The success of treating autoimmune diseases is temporary and is expressed in achieving more or less pronounced remission. The following principles of therapy are distinguished.

1. Elimination of “forbidden” clones of sensitized lymphocytes (“autoreactive lymphocytes”).

2. Removal of immunogen or adjuvant. This impact cannot always be realized. You cannot, say, remove DNA from SLE patients. On the other hand, elimination of the pathogen in the corresponding forms of diseases, toxins and other substances by plasmapheresis gives a positive result.

3. Immunosuppressive therapy should be differentiated and as short as possible.

4. Blockade of mediators of immune reactions with antihistamines, cobra venom, which destroys complement, etc.

5. Replacement therapy with necessary metabolites: for pernicious anemia - vitamin B12, for myxedema - thyroxine.

6. Anti-inflammatory drugs: corticosteroids, salicylic acid preparations.

7. Immunotherapy: desensitization with causative allergens, in the presence of immediate hypersensitivity - stimulation of the synthesis of specific IgG (or their introduction), “competing” with IgE.

8. Immunocorrection of deficiency or functional defect of T-suppressors.

As already mentioned, treatment of autoimmune diseases is aimed at reducing the number of autoantibody-producing cells, as well as lymphocytes that cause immune aggression. As a rule, therapy begins with the use of mild immunosuppressive corticosteroids. Doses of drugs depend on the disease, its severity, stages, etc. and usually range from 20 to 100 mg of prednisolone per day; in some cases, up to 200-300 mg of hormones are prescribed, but for the shortest possible period of time.

If there is no effect from the use of hormones, they move on to stronger drugs: 6-mercaptopurine (purinitol) 50-300 mg/day; imuran (azathioprine) - 50-100 mg; cyclophosphamide - 50-200 mg, methotrexate - 2.5-10 mg, vinblastine - 2-2.5 mg, the duration of use of the drugs varies. The selective immunosuppressant cyclosporine A, which selectively suppresses the function of T-lymphocytes, is being increasingly used. However, the accumulated experience is not yet sufficient. It is believed that the use of selective immunosuppressants will expand over the next 25 years.

The following are considered indications for the use of cytostatics:

Confirmed diagnosis of an autoimmune disease;

Progressive course;

Poor prognosis;

A situation where other therapeutic options have been exhausted;

Resistance to glucocorticoids;

Contraindications to GCS, for example, splenectomy;

Development of life-threatening complications of autoimmune diseases (bleeding, idiopathic thrombocytopenic purpura);

Advanced age (if possible).

Absolute indications for the use of immunosuppressive drugs are: transplantation, SLE, periarteritis nodosa, sclerodermatitis, Wegener's granulomatosis, pemphigus, Goodpasture's syndrome.

Relative indications - immune thrombocytopenia, immune hemolytic anemia, chronic progressive hepatitis, liver cirrhosis, rheumatoid arthritis, membranous glomerulonephritis.

Surgical methods are also used to treat autoimmune diseases: these include autoimmune hemolytic

anemia (splenectomy), sympathetic ophthalmia (enucleation), autoimmune pericarditis (pericardiectomy), autoimmune thyroiditis (thyroidectomy).

It seems important to administer substances to patients that are targets of autoaggression. For Hoshimoto's disease, this is thyroxine, triiodothyronine. For Addison's disease, characterized by hyperfunction of the adrenal glands, small doses of hydrocortisone: prednisolone, dexamethasone. For pernicious anemia caused by a deficiency of the active Castle factor, the administration of cyanocobalamin 100-150 mcg/day for several weeks is effective, as well as eating foods containing the missing factor, for example, raw liver. Autoimmune hemolytic anemia is treated with blood transfusions.

The prevention of autoimmune diseases also includes adequate treatment of low-grade inflammatory processes with a tendency to become chronic.

Considering the high allergenicity to medications, it seems advisable to limit analgin, amidopyrine, butadione, quinine, antibiotics and other drugs that have a pronounced ability to conjugate with blood cells and thus induce autoimmune reactions. It is also necessary to limit the intake of medications with immunostimulating properties.

In recent years, immunomodulators, primarily activators of T-suppressor mechanisms of immunity, have been actively used for the treatment of autoimmune diseases. Indications for their appointment are the nature, degree of damage to the immune system and other criteria.

Yet the standard methods of therapy used do not provide lasting results and have significant side effects. Therefore, research work continues.

In terms of prospects, transplantation of CD34+ autologous hematopoietic stem cells after chemotherapy is very encouraging. Their number increases in the blood after administration of CP and CSF or CSF alone. Often, antithymocyte globulin (4.5 mg/kg) is added to suppress their T-Lf; after 10-12 days, hematopoiesis is completely restored. Currently, extensive work has been performed on transplantation of bone marrow cells and peripheral stem cells in 536 patients with >30 autoimmune diseases.

diseases. The table provides information on most transplants (Table 4).

Table 4. Autologous transplantation of hematopoietic stem cells to patients (Europe, 2004)

This approach was a new concept of balancing the function of the immune system instead of completely killing autoreactive autoimmune lymphocytes. It should be noted, however, that this approach is most effective in the early stages of the disease, when there are no irreversible structural changes in tissue.

The principle of the proposed therapy is to implement high-dose immunosuppression (CF-2 g/m2, filgrastim - 10 mg/kg/day), which kills clones of autoreactive lymphocytes and activates the proliferation of special T-regulating cells in the thymus (they were discussed above). The subsequent transplantation of autohematopoietic stem cells provides:

1. Restoration of the number of T-regulating lymphocytes CD4+CD25+ with the expression of the FoxP3 gene, which block the proliferation of autoreactive T-lymphocyte clones.

2. Changes in the properties of autoreactive T-lymphocytes, which in autoimmune diseases have a pro-inflammatory phenotype (high expression of γ-Inf, which activates inflammation and tissue destruction), and after transplantation of hematopoietic stem cells

cells, they change their phenotype and begin to express IL-10 and the transcription factor GATA-3, which is characteristic of lymphocytes in a state of tolerance.

Thus, the implementation of the therapeutic effect of high-dose chemotherapy with hematopoietic stem cell transplantation is realized by the following mechanism:

1. Killing of many autoreactive T-lymphocytes (under the influence of chemotherapy).

2. Suppression of the activity of autoreactive T-lymphocytes by T-regulatory lymphocytes (Treg), the number of which is restored when the immune system is “restarted” from transplanted stem cells.

3. Changing the balance of cytokines - key regulators of the immune system, which eliminate the pathogenic activity of autoreactive T-lymphocytes and their tissue damage (under the influence of chemotherapy).

4. Over the past 20 years, cases of complete recovery from autoimmune diseases have already been noted.

6.2. IMMUNO COMPLEX DISEASES

Diseases with the presence of immune complexes

There are pathological processes in the pathogenesis of which immune complexes (IC) take part, i.e. connection of an antibody with an antigen. In principle, this process is a normal mechanism for removing antigen from the body. However, in some cases it may be the cause of the disease. Immune complexes come in various types: low molecular weight (they are easily excreted from the body in the urine), large ones, which are successfully captured by phagocytes and destroyed, but sometimes this process leads to the release of proteolytic enzymes and bioactive substances that damage tissue from phagocytic cells. And finally, medium-weight IR, which can thrombose capillaries, bind to complement and cause organ damage. The body has a special self-control system that limits the pathogenic effect of IR on tissue and is disrupted only in various pathologies. In general terms, the formation of IC in the circulation triggers a cascade of complement activation, which in turn solubilizes IR, i.e. transfers the insoluble immune precipitate of AG-ATs into a dissolved state, reduces their size and converts them into ICs that have lost

its biological activity. Such ICs are also called “dead-end”. In this regard, it can be assumed that one of the most important functions of complement in the body is to prevent the formation of large ICs. Apparently, this is why the formation of IC in a healthy body is quite difficult.

Diseases with the presence of immune complexes are the following.

1. Idiopathic inflammatory diseases: SLE, RA, ankylosing spondylitis, essential cryoglobulinemia, scleroderma.

2. Infectious diseases:

a) bacterial streptococcal, staphylococcal, subacute endocarditis, pneumococcal, mycoplasma, leprosy;

b) viral - hepatitis B, acute and chronic hepatitis, Dengue fever, infectious mononucleosis, CMV - disease of newborns;

3. Kidney diseases: acute glomerulonephritis, IgA nephropathy, kidney transplant.

4. Hematological and neoplastic diseases: acute lymphoblastic and myeloblastic leukemia; chronic lymphocytic leukemia; Hodgkin's disease; solid tumors affecting the lungs, chest, colon; melanoma, severe hemophilia, immune hemolytic anemia, systemic vasculitis.

5. Skin diseases: dermatitis herpetiformis, pemphigus and pemphigoid.

6. Diseases of the gastrointestinal tract: Crohn's disease, ulcerative colitis, chronic active hepatitis, primary biliary cirrhosis.

7. Neurological diseases: subacute sclerosing panencephalitis, amyotrophic lateral sclerosis.

8. Diseases of the endocrine system: Hoshimoto's thyroiditis, juvenile diabetes.

9. Iatrogenic diseases: acute serum sickness, D-penicillin nephropathy, drug-induced thrombocytopenia.

As can be seen from the presented list compiled by E. Neidiger et al. (1986), not every disease in which immune complexes are detected has elements of autoimmune reactions in its pathogenesis. One example is serum sickness.

On the other hand, diffuse glomerulonephritis and chronic rheumatism are induced by streptococcal infection, in which IR are deposited along the basement membranes of the glomerulus of the renal corpuscle (glomerulonephritis), in the heart tissue (chronic rheumatism). In turn, antibodies against cross-reacting antigens interact with streptococci, myocardial tissue, glycoproteins of heart valves, blood vessel antigens, etc.

Atherosclerosis, endarteritis and other pathological processes are accompanied by the deposition of immune complexes on the inner wall of blood vessels, causing their diffuse inflammation.

It should be especially noted that IR plays a crucial role in the development of various systemic vasculitis, which is based on generalized vascular damage with secondary involvement of various organs and tissues in the pathological process. The commonality of their pathogenesis is a violation of immune homeostasis with the uncontrolled formation of autoAb, IC, circulating in the bloodstream and fixing in the wall of blood vessels with the development of a severe inflammatory reaction. This concerns hemorrhagic vasculitis(Henoch-Schönlein disease), when IR containing IgA is deposited in the wall of blood vessels, with the subsequent development of inflammation, increased vascular permeability, and the appearance of hemorrhagic syndrome. IR is equally important when Wegener's granulomatosis, when the level of serum and secretory IgA increases, IC are formed and fixed in the vascular wall. Periarteritis nodosa According to their pathogenesis, they are also classified as immune complex diseases with complement activation. Typical features of immune complex inflammation are observed. Hemorheological disorders and the development of disseminated intravascular coagulation syndrome are of great importance. Moreover, one of the key reasons for the development of DIC is also considered to be the primary effect of immune complexes on platelets. There is an opinion that in serum sickness, SLE, post-streptococcal glomerulonephritis, immune complex damage is responsible for the main clinical manifestations of the disease.

Diagnosis of immune complex diseases

Immune complexes are detected by various methods in blood or tissues. In the latter case, anti-complementary antibodies labeled with fluorochromes and anti-IgG, IgM, IgA enzymes are used, which detect these substrates in IR.

Treatment of diseases associated with immune complexes

Treatment of diseases associated with immune complexes includes the following approaches.

2. Removal of antibodies: immunosuppression, specific hemosorption, blood cytopheresis, plasmapheresis.

3. Removal of immune complexes: exchange transfusions of plasma, hemosorption of complexes.

To this we can add the use of immunomodulators that stimulate the function and motility of phagocytic cells.

As can be seen from these data, immune complex diseases are closely related to autoimmune diseases, often occur simultaneously with them, and are diagnosed and treated in approximately the same way.

AUTOIMMUNIZATION AND IMMUNODEFICIENCY SYNDROMES

Autoimmunization - a pathological process based on the development of immune reactions to antigens of the body’s own tissues.

The development of an immune reaction against self-antigens is the cause of some human diseases, although autoantibodies can be found in the serum or tissues of many healthy people, especially in the older age group. Harmless antibodies are formed after tissue damage and play a physiological role in removing destruction products. In addition, a normal immune response is required to recognize self-histocompatibility antigens. Autoimmune diseases - a group of diseases that are based on the development of immune reactions to the body’s own tissues.

There are three main signs of autoimmune diseases:

▲ presence of an autoimmune reaction;

▲ the presence of clinical and experimental data that such a reaction to tissue damage is not secondary, but has a primary pathogenetic significance;

▲ absence of other specific causes of the disease.

Naturally, these signs are observed only in a few diseases, for example, systemic lupus erythematosus.

There are autoimmune diseases in which autoantibodies are directed against a single organ or tissue, then this organ or tissue is affected. For example, in Hashimoto's thyroiditis, the antibodies are absolutely specific to the thyroid gland. At the same time, diseases with the formation of various antibodies are possible, which leads to multiple organ damage. Thus, in systemic lupus erythematosus, autoantibodies react with components of the nuclei of various cells; in Goodpasture syndrome, antibodies against the basement membrane of the lungs and kidneys (cross-reacting) cause damage only to these organs. Obviously, autoimmunity involves a loss of self-tolerance.

The pathogenesis of autoimmunization appears to involve immunological, genetic and viral factors interacting through complex mechanisms that are still little known. The most likely ones are the following.

1. Helper T cell tolerance bypass. Self-antigen tolerance is often caused by clonal deletion or anergy of specific T lymphocytes in the presence of fully competent hapten-specific B lymphocytes. However, tolerance can be broken by one of two mechanisms.

Molecular mimicry. Some infectious agents cross-react with human tissue through their hapten determinants. Microorganisms can cause an antigenic response by cross-reacting hapten determinants in association with their own carrier, to which helper T lymphocytes are intolerant. The antibody produced in this way can damage tissues that are associated with cross-reacting determinants. It is therefore clear that rheumatic heart damage sometimes develops following streptococcal infection, since antibodies to streptococcal M protein cross-react with M protein in the sarcolemma of the heart muscle.

2. Polyclonal activation of lymphocytes. Some microorganisms and their metabolic products can cause polyclonal (antigen-nonspecific) activation of B lymphocytes. The best studied is bacterial lipopolysaccharide (endotoxin), which can induce mouse lymphocytes in vitro to form antibodies against DNA of thymocytes and erythrocytes. Infecting cells with the Epstein-Barr virus can give the same results, since human B lymphocytes have receptors for this virus.

3. Imbalance of functions spring soup and T-lymphocyte helpers. A decrease in the functional activity of suppressor T cells contributes to the development of autoimmunization and, conversely, excessive activity of helper T cells can cause an increase in the production of autoantibodies by B cells. For example, in human systemic lupus erythematosus, there is a dysfunction or decrease in the content (sometimes both at the same time) of suppressor T cells and activation of helper T cells.

4. The appearance of sequestered antigen. Any autoantigen that is completely sequestered during development is considered foreign if it enters the bloodstream and an immune response develops against it. Sperm, myelin basic protein, and lens crystallin may fall into the category of antigens. For example, trauma to the testicles promotes the release of sperm into the tissue; after this, antibodies to sperm appear.

5. Genetic factors of immunity. These factors determine the frequency and nature of autoimmune diseases. First, there is a familial predisposition to certain human autoimmune diseases, such as systemic lupus erythematosus, autoimmune hemolytic anemia, and autoimmune thyroiditis. Secondly, there is a connection between some autoimmune diseases and antigens of the HLA system, especially class II antigens. For example, most people with rheumatoid arthritis (an autoimmune joint disease) have HLA-DR4 or HLA-DR1, or both.

6. Microbial agents in autoimmunity. Various microorganisms, including bacteria, mycoplasmas and viruses, may be involved in the development of autoimmunity. First, viral antigens and self-antigens can bind to form immunogenic units. Second, some viruses, such as Epstein-Barr virus, are nonspecific, polyclonal B-lymphocyte mitogens and can induce the formation of autoantibodies. Third, viral infection can lead to decreased suppressor T cell function.

Viruses and some other microorganisms, such as streptococci and Klebsiella, may have epitopes that cross-react with autoantigens. Some infectious agents cause strong activation and proliferation of CO4+T lymphocytes.

It has been established that autoimmunization of the body can result from:

• 1) Release of sequestered antigens into the bloodstream. It is known that these antigens do not participate in the mechanism of negative selection of T- and B-lymphocytes in the thymus and bone marrow, and tolerance does not develop to them among these cells. The interaction of immunocompetent cells with such antigens always leads to the induction of an immune response followed by an immune reaction to these antigens. Examples of sequestered antigens are: myelin basic protein, normally separated from the immune system by the blood-brain barrier, sperm antigens and eye lens antigens. It has been established that during injuries, inflammatory diseases, viral and bacterial infections, these antigens enter the bloodstream;
• 2) The appearance of new antigenic determinants on cells and tissues. This may be the result of a metabolic disorder in tissues and cells (a defect in the synthesis of macromolecules, a violation of their hydrolysis in lysosomes, abnormal protein glycosylation, etc.), modification of cell membranes under the influence of medicinal and toxic substances, a viral infection, or the formation of a single antigenic determinant by an autoantigen with a viral peptide or a medicine. Antibodies that appear during the immunization process, due to their ability to cross-react, are capable of attacking normal tissue and inducing inflammatory-destructive processes in it;
• 3) Molecular mimicry. It has been established that a number of viruses and bacteria contain antigenic determinants identical or similar to human ones. A study of about 600 virus-specific sera capable of reacting with 11 types of viruses showed that in 3% of cases they react with high activity with normal human tissues. These data support the view that molecular mimicry is quite common and common.

The data presented in Table 11-2 indicate that molecular mimicry exists between a wide variety of infectious agents and structures of the human body. In this regard, it should be remembered that the antigenic determinants of proteins (i.e., those formations that induce immune reactions and with which the products of the immune response interact) are often represented by several (7-10) amino acid residues.

The role of molecular mimicry in the development of autoimmune pathology is well demonstrated by the following data: the development of autoimmune encephalitis after immunization of rabbits with the hepatitis B virus polymerase peptide, which is 60% homologous to the human myelin basic protein peptide; the development of myocarditis during streptococcal infection, when antistreptococcal antibodies reveal high reactivity to cardiac muscle antigens, etc. These observations indicate that protective antibodies (cells) produced in response to infection, due to the ability to cross-react with similar structures, can induce autoimmune tissue damage .

4) Increased and atypical expression of HLA molecules on cells. An immunological study of insulin-dependent DIABETES MELLITUS showed that in individuals with this pathology, pancreatic beta cells express class I HLA antigens at a high density, significantly greater than in healthy individuals, as well as class II HLA antigens in large quantities, which cells are not normally expressed at all. Similar data were obtained in the study of Graves' disease. In patients, atypical expression of class II HLA antigens is observed on the glandular cells of the thyroid gland.

It is believed that atypical expression of HLA class II antigens on beta cells of the pancreas and glandular cells of the thyroid gland and their abnormal presentation of antigen are a trigger for autoimmunization of the body. This opinion also has convincing experimental confirmation. Using transgenic mice, it was shown that induction of expression of MHC class 2 molecules on pancreatic beta cells leads to the development of diabetes, which is accompanied by a pattern of lymphocytic infiltration of the islets of Langerhans. Increased, atypical expression of class II HLA antigens on cells that do not normally express it can be induced by substances of both microbial origin and endogenous origin.

In vitro experiments have shown that under the influence of INF-gamma, the expression of class II HLA antigens occurs on various types of cells: intestinal epithelial cells, beta cells of the pancreas, glandular cells of the thyroid gland, hepatocytes, kidney cells. It is noteworthy that in patients with systemic lupus erythematosus during the active course of the disease, an increased level of INF-gamma is observed in the serum. It is known that infections, inflammation, and injuries can act as inducers of this cytokine. An important property of INF-gamma is its ability to induce the production of a number of cytokines, including IL-1. In the development of autoimmune reactions, as follows from a number of studies, this interleukin can act as a costimulator of the activation of clones of autoreactive T lymphocytes.

5) Polyclonal activation of B lymphocytes.

It is known that polyclonal B-cell activation can lead to the production of antibodies of different specificities. When clones of autoreactive B lymphocytes are activated by this mechanism, the resulting autoantibodies are believed to be capable of acting as a trigger for the disease. Many viruses (cytomegalovirus, Epstein-Barr virus, measles virus), bacteria (gram-negative) and their components (toxins, DNA, proteolytic enzymes) have the properties of polyclonal activators. In this regard, it should be noted that systemic autoimmune diseases are always accompanied by the production of autoantibodies of very different specificity: antinuclear, anti-DNA, antibodies to collagen, elastin, T- and B-lymphocytes, platelets, erythrocytes, etc.

It is important to emphasize that the clinical and experimental material accumulated to date indicates the multifactorial etiology of autoimmune diseases. It should also be added that according to modern data, there is a genetic determinacy of their development. It has been established that predisposition to autoimmunopathology is controlled by several genes, some of which are located in the major histocompatibility complex. It has been proven that most autoimmune diseases are associated with the presence of the following antigens in the HLA phenotype: DR2, DR3, DR4, DR5. Rheumatoid arthritis is associated with HLA-DR4, Hashimoto's thyroiditis - with HLA-DR5, multiple sclerosis - with HLA-DR2, systemic lupus erythematosus - with HLA-DR3. Autoimmune diseases develop much more often in women than in men.

Clinical and experimental data indicate that the development of autoimmune diseases is based on the same mechanisms that the immune system uses to protect the body from exogenous intervention - antibodies, cytotoxic T-lymphocytes. The experiment established that helper T-lymphocytes (CD4+ cells) play a leading role in the formation of autoimmune processes. Using a model of experimental autoimmune encephalitis, thyroiditis and arthritis, it was established that these diseases can be transferred from sick animals to healthy animals using sensitized T-helper cells, and also suppressed by administering anti-CD4+ antibodies to animals, which eliminate or suppress the activity of helper T-lymphocytes. The results obtained from the study of experimental encephalitis indicate that the quantitative ratio of Tn1 and Tn2 cells plays a significant role in the development of autoimmune diseases: Tn1 cells contribute to the development of the process, and Tn2 cells, on the contrary, block it.

The main pathways for the development of autoimmune reactions are shown in Figure 11-4. In the event of the development of a cellular immune reaction, effector autoreactive T-killers are formed from naïve T-cytotoxic cells with the help of Tn cells. Sensitization of naïve T-cytotoxic lymphocytes occurs when they interact with a self-antigen presented either by the target cells themselves or by antigen-presenting cells in complex with MHC class I molecules. Formed killer T-cells, when they encounter cells carrying this autoantigen (target cells), interact with them using a specific receptor and, through the production of perforins, cause their lysis. Target cell death can also be induced by fragmentins and Fas ligand. In this case, cell death develops through apoptosis. This mechanism of development of autoimmune pathology is characteristic of insulin-dependent DIABETES MELLITUS and multiple multiple sclerosis.

In the event of the development of a humoral immune reaction to a self-antigen, plasma cells are formed from B lymphocytes, with or without the help of T lymphocytes. The autoantibodies they produce can have the following effects:

• 1) lyse cells carrying a specific autoantigen (with the involvement of the complement system in the process). (This mechanism underlies the development of autoimmune hemolytic anemia, Goodpasture syndrome and other diseases);
• 2) have a stimulating effect when interacting with the corresponding antigenic structure. (This result is observed in Graves' disease. Produced autoantibodies to the thyroid-stimulating receptor of thyroid cells, interacting with it, cause unregulated hyperactivation of the thyroid gland, which leads to the development of thyrotoxicosis);
• 3) have a blocking effect. (This effect underlies myasthenia gravis. The autoantibodies produced during this disease suppress the functioning of acetylcholine receptors at neuromuscular synapses and also cause their degradation, which is the cause of the development of the disease);
• 4) form immune complexes by interacting with soluble antigens. (The toxic effect of immune complexes underlies the development of diseases such as post-streptococcal glomerulonephritis, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus). The tissue-damaging effect of immune complexes lies in their ability to activate the complement system, concentrate granulocytes and monocytes at the site of their deposition, and also activate these cells. Activation of granulocytes and monocytes leads to the production of proteolytic enzymes and polycationic proteins into the surrounding tissues, which, together with activated complement components (MAC, C3a, C5a), cause inflammatory-dystrophic processes in tissues.

The immune system is a complex mechanism consisting of cells and organs. Its main task is to protect humans from the influence of foreign agents. Perfectly distinguishing “strangers” from “friends,” it protects the body from many different pathologies. But sometimes it fails. The immune system loses the ability to distinguish between its cells. The body begins to produce antibodies that attack healthy tissue. In this case, doctors conclude: disturbed autoimmune processes are occurring. What does this mean? And how to deal with such phenomena?

Autoimmune processes in the body - what is it?

Most people who hear about such phenomena immediately associate them with severe incurable diseases. This is true. But only if the autoimmune processes are disrupted. If they are normal, then they perform very necessary and important functions.

Let's figure out what an autoimmune process means. During human life, any disturbances may occur in cells. In this case, they become foreign and can even cause harm. This is where the immune system comes into play. It cleanses the body and rids it of foreign agents. The immune system eliminates dead cells. It is difficult to even imagine what would happen to the body if such a function did not exist. A person would turn into a real cemetery of dead cells. It is this function that is called the “autoimmune process in the body.”

In case of failure, the immune system begins to attack its own cells. It perceives healthy tissues as foreign elements. As a result, their own immune system damages them. Against the background of this phenomenon,

Reasons for violations

Until today, doctors are not ready to say why autoimmune processes are disrupted. The reasons for such phenomena are not fully understood. There is an opinion that such pathologies can be triggered by injuries, stress, hypothermia, and various infections.

Doctors identify the following sources that trigger such disorders in the body:

1. Various infectious pathologies provoked by microorganisms whose protein structure is very similar to human tissues and organs. For example, very often the source of the problem is streptococcus. This infection invades a cell, disrupts its functioning and infects neighboring ones. The protein resembles healthy tissue cells. The immune system is unable to distinguish between them. As a result, a person may develop ailments such as arthritis, autoimmune glomerulonephritis, and gonorrhea.
2. In the body, as a result of a number of reasons, pathological disorders such as necrosis or tissue destruction can be observed. The immune system, trying to cope with them, begins to attack not only the affected cells, but also healthy tissues. For example, hepatitis B often becomes chronic.
3. Rupture of blood vessels. Many organs do not come into contact with this liquid. After all, blood does not fill the entire cavity of the body, but flows through special vessels. But sometimes veins can rupture. In this case, bleeding will begin. The body will immediately react to this phenomenon, perceiving the cells as foreign, and will launch the production of antibodies. Such disorders can lead to thyroiditis and autoimmune prostatitis.
4. The source of the problem may be an immunological imbalance or a hyperimmune state.

At-risk groups

The autoimmune process in the body can be disrupted in any person. However, doctors identify certain groups of people who are most susceptible to this pathology.

1. Women of childbearing age. It has been noticed that young ladies suffer from these disorders much more often than men. In this case, the pathology often develops during reproductive age.
2. People with similar illnesses in their family. Some autoimmune pathologies are genetic in nature. Such a disease is Hereditary predisposition, especially in combination with other factors, often becomes a trigger for the development of pathology.
3. Individuals who have a lot of contact with certain components of the environment. Some substances can become a source of disease development or aggravate existing ones. Such provoking factors are: bacterial, viral infections; chemicals; active sun.
4. People of a certain ethnicity. Doctors state that mainly white people develop a pathology such as type 1 diabetes. in severe stages, most often affects Spaniards and African Americans.

General symptoms

Each case of this disease is quite unique. The symptoms that occur in a person depend on which tissues are attacked. However, there are common marker symptoms that indicate a disturbed autoimmune process.

Signs characterizing a malfunction in the body:

1. The patient experiences dizziness, general weakness, and low-grade fever.
2. Most autoimmune pathologies occur in a chronic form. Stages of remission alternate with exacerbations. Sometimes the pathology progresses rapidly, leading to severe complications in just a few days, weeks, months.

Diseases and symptoms

Let us consider in more detail what ailments can develop as a result of such a condition as a disturbed autoimmune process. Symptoms depend entirely on the pathology. Therefore, it is impossible to talk about them separately.

So, if the autoimmune system is disturbed, the following may develop:

Alopecia areata

Hair follicles are attacked. This pathology, as a rule, does not affect the general health. But it significantly worsens the appearance.

The disease is characterized by the following symptoms: there are no patches of hair on the head and other areas of the body.

Autoimmune hepatitis

With this pathology, the immune system destroys the liver. As a result, organ compaction, cirrhosis, and liver failure may occur.

• liver enlargement,
• skin itching,
• weakness,
• jaundice,
• joint pain,
• discomfort in the gastrointestinal tract.

Antiphospholipid syndrome

Against the background of thrombosis of veins and arteries, damage to blood vessels occurs.

The development of such a pathology is indicated by:

• presence of blood clots,
• mesh rash on wrists, knees,
• spontaneous abortions.

Celiac disease

With this pathology, people are gluten intolerant. This is a substance found in rice, grains, and barley. When these foods or certain medications are taken, the system attacks the intestinal lining.

Symptoms:

• pain, bloating;
• upset or constipation;
• weight loss or weight gain;
• weakness, rash, itching on the skin;
• disrupted menstrual cycle, miscarriage, infertility.

Graves' disease

This is a pathology in which a disturbed autoimmune process occurs in the thyroid gland. The affected organ begins to produce a lot of hormones.

The disease is characterized by:

• irritability,
• increased sweating,
• weight loss,
• insomnia,
• trembling hands
• minor menstruation,
• hair section,
• high heat demand
• bulging eyes,
• muscle weakness.

Type 1 diabetes

In this case, those cells that produce insulin are attacked. This hormone ensures normal blood sugar levels. Without insulin, the norm is significantly exceeded. As a result, damage to the heart, kidneys, eyes, teeth, and nerves may occur.

The symptoms of this disease are:

• feeling of thirst,
• feeling tired, hungry,
• itching, dry skin,
• frequent urination,
• poor wound healing,
• involuntary weight loss,
• tingling or loss of sensation in the limbs,
• visual impairment (the image is perceived as blurry).

Multiple sclerosis

Characteristic damage to the nerve sheath. Damage affects the brain and spinal cord. Symptoms vary depending on the extent and area of ​​the lesion.

The following signs may be observed:

• poor coordination, loss of balance, weakness;
• speech problems;
• tremor;
• paralysis;
• tingling, numbness of the limbs.

Psoriasis

The disease develops as a result of the active production of new skin cells in the deep layers. They begin to accumulate on the surface of the epidermis.

The disease manifests itself with the following symptoms:

• red, rough spots that resemble scales;
• they appear on the elbows, knees, head;
• pain and itching appears.

A specific form of arthritis may develop that affects the joints of the fingers. When the sacrum is involved in the process, pain and discomfort occurs in the back.

Hashimoto's disease

This is another disease in which the autoimmune process in the thyroid gland is disrupted. But this pathology is characterized by insufficient production of hormones.

The disease is indicated by:

• fatigue, weakness;
• sudden weight gain;
• increased sensitivity to cold;
• discomfort in muscle tissue;
• poor joint mobility;
• constipation;
• swelling of the face.

Rheumatoid arthritis

The immune system begins to attack the lining of the joints.

The following manifestations are characteristic:

• pain, poor mobility in joints;
• joints become swollen and deformed;
• movements are significantly limited;
• fatigue, fever appears;
• Knob-like subcutaneous formations may be observed, most often on the elbows.

Diagnosis of pathology

How can you determine the development of the disease? In diagnosing diseases, one of the most important points is identifying the immune factor that provoked tissue damage.

In addition, the hereditary factor is taken into account. It is very important to inform your doctor about all symptoms that arise, even those that, at first glance, seem insignificant.

Special tests are required. The autoimmune inflammatory process cannot go unnoticed. It can be detected by testing for antibodies in the blood. Various immunological laboratory examination methods may also be prescribed.

Who to contact?

Quite often, people whose autoimmune processes are disrupted do not know which doctor to visit. This is not surprising, because pathology can affect a variety of systems.

It is best to consult a therapist initially. Depending on which organs are affected, the doctor will refer the patient to a specialist.

This could be: endocrinologist, gastroenterologist, dermatologist, hepatologist, rheumatologist, hematologist, gynecologist, urologist.

In addition, you will need the help of a psychotherapist, psychologist and nutritionist.

Treatment methods

Is it possible to fight this pathology? Today, treatment of the autoimmune process is carried out quite successfully thanks to numerous studies by specialists. When prescribing medications, doctors take into account that the immune system is the main factor that negatively affects the body. Accordingly, therapy is designed to reduce its activity or restore the necessary balance.

For autoimmune diseases, medications are prescribed:

1. Immunosuppressants. Such drugs have a depressing effect on the functioning of the immune system. This category includes: antimetabolites, cytostatics, corticosteroid hormones, some antibiotics. The use of these drugs allows you to stop the inflammatory process and significantly reduce the activity of the immune system. However, immunosuppressants have a number of negative reactions. After all, they affect the entire body. Sometimes hematopoiesis may be impaired, high susceptibility to infection may occur, and internal organs may be affected. That is why these medications can only be prescribed by a doctor, after a complete check of the body. In this case, therapy must be carried out under the supervision of a competent specialist.
2. Immunomodulators. These medications are prescribed to achieve a balance between the various components of the immune system. As a rule, these medications are of natural origin. The most commonly prescribed drugs are: Alfetin, Echinacea purpurea, Rhodiola rosea, Ginseng extract.

Lifestyle

People who have impaired autoimmune processes need to follow certain rules. They will help improve your well-being and reduce the number of exacerbations. But they should be performed regularly.

1. Work with a nutritionist to develop an appropriate diet. Patients need to eat enough vegetables, fruits, low-fat dairy products, whole grains and plant proteins. And it is better to avoid excess sugar, salt, and saturated fats.
2. Play sports. Be sure to discuss with your doctor what kind of activity is recommended for you. Exercise is very beneficial for people suffering from joint and muscle pain.
3. Provide adequate rest. It allows the body to recover. For people who don't get enough sleep, symptom severity and stress levels increase significantly. As a rule, a person needs 7-9 hours for proper rest.
4. Protect yourself from stress. Constant anxiety can lead to an exacerbation of an autoimmune disease. That is why patients need to find methods and techniques to cope with stress. Quite effective techniques are: self-hypnosis, meditation, visualization.

Conclusion

Unfortunately, it is impossible to get rid of an autoimmune disease. But this does not mean that you cannot enjoy life with such an illness. Be sure to follow all the doctor’s recommendations, take the treatment prescribed by him, and visit the doctor according to the prescribed schedule. This will significantly reduce unpleasant symptoms, which means you can continue to enjoy life.