Physiological aspects and norm
In pathological anatomy, it is important to understand that the production of autoantibodies is not always a sign of disease. Normally, the human immune system is capable of interacting with its own tissues without destroying them.
Autoantibodies can be detected in the blood serum and tissues of absolutely healthy individuals. This phenomenon is particularly common in the older age group. Such antibodies serve an important physiological function: they are formed after tissue damage and are necessary for the efficient clearance of cellular debris. Furthermore, a normal, physiologically adequate immune response is critically important for the proper recognition of self-histocompatibility antigens, which prevents the development of pathological aggression against healthy cells.
Three main signs of autoimmune pathology
To classify a disease as autoimmune, simply detecting antibodies in the blood is not enough. The diagnosis is based on a strict triad of signs:
- Presence of an autoimmune reaction. The very fact of aggression against self-antigens must be documented.
- Primary pathogenetic significance. Clinical and experimental data are required to unequivocally confirm that this specific reaction triggers the disease rather than being its secondary consequence.
- Absence of other causes. The developed disease must not have other definite causes capable of fully explaining the observed clinical picture.
Only when all three conditions are strictly met is the pathology recognized as truly autoimmune.
Classification by direction of action
Depending on which structures become the target of autoantibodies, all autoimmune diseases are divided into three main groups:
- Organ-specific. Cause strictly localized damage. In this case, antibodies are directed against a single organ or specific tissue. Example: Hashimoto's thyroiditis (Hashimoto's goiter), in which antibodies are specific exclusively to thyroid tissues.
- Systemic. Lead to generalized damage throughout the body. Autoantibodies in such diseases react with components of cell nuclei in various tissues, causing widespread disorders. Example: systemic lupus erythematosus (SLE).
- Intermediate. Characterized by selective involvement of several organs. Example: Goodpasture syndrome, in which antibodies attack the basement membrane in only two organs — the lungs and kidneys.
Etiology
The fundamental cause triggering the development of any autoimmune disease is the loss of autotolerance. Normally, immunity is tolerant to self-tissues, but upon loss of this property, self-cells begin to be recognized as foreign antigens, which leads to their destruction. This failure in the recognition system underlies the pathogenesis of all diseases in this group, regardless of whether a single organ or the entire organism is affected.
Briefly: answers to topical questions
Which specific antibodies to cell nuclear components are characteristic of systemic lupus erythematosus?
Systemic lupus erythematosus is characterized by the formation of a heterogeneous pool of antinuclear antibodies (ANA) directed against various intracellular structures. Specific profile antibodies include:
- Anti-double-stranded DNA antibodies (anti-dsDNA) — possess high specificity for this disease and are detected in 20–70% of patients.
- Anti-histone antibodies — found in the majority of patients and serve as a marker for drug-induced lupus.
- Anti-Sm antibodies (anti-Sm) — directed against ribonucleoprotein complexes (small nuclear RNA polypeptides) and exhibit the highest specificity.
The screening pool also includes autoantibodies to nucleoli and centromeres.
What pathogenetic mechanisms lead to the loss of autotolerance by the immune system?
The loss of autotolerance by the immune system is caused by a complex of central and peripheral mechanisms. The main pathogenetic processes include:
- Impaired central tolerance — defects in negative selection of T cells in the thymus.
- Impaired peripheral tolerance — deficiency of regulatory T cells, inflammation, and polyclonal stimulation.
- Molecular mimicry — a cross-reactive immune response due to antigenic similarity between microorganisms and self-tissues.
- Modification of self-antigens — alteration of protein structure under the action of infectious agents or their denaturation.
- Release of sequestered antigens — exposure of intracellular proteins with which the immune system does not normally come into contact.
- Production of anti-idiotypic antibodies and stimulation via innate immune receptors.
Which diseases belong to organ-specific autoimmune diseases, aside from Hashimoto's thyroiditis?
Organ-specific autoimmune diseases in which the immunopathological process is restricted to a single tissue or organ, aside from Hashimoto's thyroiditis, include:
- Atrophic gastritis.
- Insulin-dependent type 1 diabetes mellitus — characterized by the destruction of pancreatic islet β-cells.
- Autoimmune hemolytic anemia.
- Autoimmune oophoritis — localized damage to ovarian tissues.
What general pathological morphological changes in tissues are characteristic of autoimmune diseases?
Sources for autoimmune and rheumatic processes indicate the following morphological changes:
- Plasmacytic transformation and hyperplasia of lymphoid tissue.
- Polyserositis.
- Vasculitis with mucoid and fibrinoid swelling of the vascular wall; fibrinoid necrosis and vascular thrombosis are possible.
- In the rheumatic process — the formation of specific rheumatic granulomas in the perivascular stroma.
- Sclerosis of vessels and tissues.
What is the role of major histocompatibility complex antigens in genetic predisposition to autoimmune diseases?
Major histocompatibility complex (HLA) antigens play a key role in genetic predisposition to autoimmune diseases, which is confirmed by the association of specific pathologies with particular alleles:
- MHC-I molecules (HLA-I) — associated with diseases mediated by cytotoxic T cells. For example, carriage of the HLA-B27 allele causes a high risk of ankylosing spondylitis and acute anterior uveitis.
- MHC-II molecules (HLA-II) — more commonly linked to autoimmune pathology (rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus). Goodpasture syndrome is associated with HLA-DR2.
- Specific polymorphisms — in type 1 diabetes mellitus, an amino acid substitution at position 57 of the DQβ1 molecule is critical, while juvenile dermatomyositis is associated with the HLA-DQA1*0501 and HLA-DR3 alleles.
For quick memorization of the classification, use the mnemonic O-S-I: Organ-specific (one organ, locally), Systemic (nuclei of various cells, entire body), Intermediate (selectively several organs).
Class and exam questions
Does the presence of autoantibodies in the blood always indicate the development of an autoimmune disease?
No, not always. Normally, autoantibodies may be present in the blood serum and tissues of healthy individuals, which is particularly common in the older age group. Their physiological role consists of binding and clearing cell debris following tissue damage.
What conditions are necessary for a pathology to be recognized as autoimmune?
A coincidence of three factors is required: the presence of the autoimmune reaction itself, confirmation of its primary pathogenetic significance (clinically or experimentally), and the complete absence of other definite causes capable of causing the given disease.
What is the difference between systemic and organ-specific autoimmune diseases?
In organ-specific diseases (e.g., Hashimoto's thyroiditis), antibodies attack only one specific organ. In systemic diseases (such as systemic lupus erythematosus), autoantibodies react with nuclear components of various cells, causing damage throughout the body.
What else to study on this topic
- Mechanisms of recognition of self-histocompatibility antigens in health and disease.
- The physiological role of autoantibodies in the utilization of damaged tissue debris.
- Pathogenesis and morphological changes in Hashimoto's thyroiditis (Hashimoto's goiter).
- Systemic lupus erythematosus: mechanisms of autoantibody reaction with cell nuclear components.
- Goodpasture syndrome as an example of an intermediate autoimmune disease involving the lungs and kidneys.
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