Initial Links of Pathogenesis
Under the influence of various pathogenic factors, processes are triggered in the body that lead to the development of immune autoaggression. In antigen-dependent forms, four main initiation mechanisms are distinguished:
- Loss of natural tolerance to the body's own antigens (Ags).
- Introduction from the outside of antigens that are structurally similar to endogenous ones (the molecular mimicry phenomenon).
- Modification of the body's own antigens.
- Genome modification (various mutations) of own cells.
Loss of tolerance and "immune-privileged" organs
This mechanism is key to the development of pathologies of the so-called "immune-privileged" organs. During prenatal ontogenesis, certain tissues form under conditions of strict isolation—they are separated from the rest of the body by histohematological barriers. Because of this, they have never had contact with immunocompetent lymphocytes.
In the postnatal period, the immune surveillance system perceives such tissues as "foreign", despite the fact that genetically they are completely "self". Typical "immune-privileged" structures include:
- Spermatozoa proteins.
- Lens of the eye.
- Myelin (forms the sheaths of nervous tissue).
- Colloid of thyroid cells.
Autoaggression is triggered when the integrity of histohematological barriers is compromised. Causes of such destruction can include tissue trauma, active inflammation, or necrosis. As soon as the barrier falls, "immune-privileged" Ags come into contact with immune system cells, natural tolerance is lifted, and the attack begins.
Clinical examples:
- Thyroiditis — autoimmune lesion of the thyroid gland.
- Sympathetic ophthalmia — a severe lesion of a healthy eye occurring after trauma to the partner eye.
- Orchitis — autoimmune inflammation of testicular tissue.
- Encephalitis — autoimmune lesion of brain structures.
Modification of own antigens
The essence of this mechanism is that the body's own tissue antigens undergo changes. This modification makes them a new, unrecognized target for the immune system, which begins to perceive them as a threat.
The main causes of such modification include:
- Components of destroyed microorganisms.
- Components of various fungi.
- Unicellular and multicellular parasites.
- Specific metabolites of all the above-mentioned infectious agents.
Molecular mimicry phenomenon
The molecular mimicry phenomenon underlies cross-immune autoaggression. The mechanism develops according to the following scenario: a foreign antigen acting as a carrier of information is introduced into the body. In response to this invasion, the immune system begins to actively produce specific immunoglobulins (Ig). However, the resulting Ig begin to act not only against the foreign agent, but also against the body's own structures with a similar structure.
Examples of pathologies with this mechanism:
- Autoaggressive hemolytic anemias occurring against the background of leishmaniasis.
- Diffuse glomerulonephritis, which manifests upon infection with β-hemolytic streptococcus.
- Enterocolitis in patients infected with pathogenic strains of Escherichia coli.
- Myocarditis developing after a previous streptococcal infection (tonsillitis, pneumonia, or sinusitis). In this case, the antigenic determinant of the streptococcal M-protein is structurally very similar to the M-protein antigen located on the cell membrane of own cardiomyocytes.
Principles of therapy
The treatment of immune-independent autoimmune diseases requires an integrated approach. Therapy is always based on a competent combination of three directions: etiotropic (elimination of the root cause, e.g., an infectious agent), pathogenetic (interruption of autoaggression mechanisms), and symptomatic (relief of clinical manifestations in the patient).
Briefly: answers to topical questions
What pathogenic factors cause modification of the genome of own cells during the initiation of autoaggression?
The pathogenic factors causing the modification of the genome of own cells are viruses and bacteria. This mechanism initiates autoaggression by introducing foreign DNA or its fragment into the genome of the host somatic cell. A hybrid genome is formed, synthesizing new proteins, which provokes a reaction of the immune surveillance system against such cells.
Examples of foreign DNA integration:
- Hepatitis B virus — incorporated into liver cells.
- Herpesviruses — integrate into various somatic cells.
- Epstein-Barr virus — integrates into the genome of lymphocytes.
The four triggering mechanisms are easy to remember by the acronym TMMM: loss of Tolerance, Molecular mimicry, Modification of antigens, Mutations of the genome.
Class and exam questions
Why are immune-independent diseases called antigen-dependent?
Because they develop independently of dysfunctions within the immune surveillance system itself. The primary cause is the emergence of a triggering antigen—a modified self-antigen, a "sequestered" barrier antigen, or a foreign antigen mimicking it.
What are "immune-privileged" tissues and why does immunity attack them?
These are tissues (e.g., lens, myelin) that were isolated by histohematological barriers during the intrauterine period and did not contact lymphocytes. During trauma or inflammation, the barrier collapses, and the immunity reacts to them as foreign objects.
How can tonsillitis lead to autoimmune myocarditis?
Here, the molecular mimicry phenomenon comes into play. Antibodies produced by the body against the streptococcal M-protein, due to structural similarity, begin to mistakenly attack the M-protein on the membranes of healthy heart cells (cardiomyocytes).
What else to study on this topic
- The role of necrosis and inflammation in the destruction of histohematological barriers.
- Pathogenesis of sympathetic ophthalmia in trauma to the partner eye.
- Mechanisms of cross-immune autoaggression in leishmaniasis.
- The effect of fungal and parasite metabolites on the modification of own antigens.
- Cell genome mutations as a factor in the development of autoaggression.
Master the entire topic in the "Pathophysiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Immune-independent autoimmune diseases" and another 4,913 pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 135 video lessons on the subject
Other topics from "Chapter 16. IMMUNOPATHOLOGICAL CONDITIONS"
Free video lessons: pathophysiologyShort lessons with lecture notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.