Initial Pathogenetic Links
Under the influence of various pathogenic factors, processes are initiated in the body that lead to immune self-aggression. In antigen-dependent forms, there are four main initiation mechanisms:
- Breakdown of natural tolerance to the body's own antigens (Ags).
- Introduction of exogenous antigens that are structurally similar to endogenous ones (the phenomenon of molecular mimicry).
- Modification of the host's own antigens.
- Genome modification (various mutations) of host cells.
Loss of Tolerance and "Privileged" Organs
This mechanism is crucial for the development of pathologies in so-called immune-privileged ("barrier") organs. During prenatal development, certain tissues form under strict isolation—separated from the rest of the body by blood-tissue barriers. Consequently, they never make contact with immunocompetent lymphocytes.
In the postnatal period, the immune surveillance system perceives such tissues as "foreign," despite them being genetically identical to the host. Typical immune-privileged structures include:
- Spermatozoal proteins
- Lens of the eye
- Myelin (forming nervous tissue sheaths)
- Colloid of thyroid follicles
Autoaggression is triggered when the integrity of these blood-tissue barriers is compromised. Causes of such breakdown include tissue trauma, active inflammation, or necrosis. Once the barrier fails, sequestered antigens contact immune system cells, natural tolerance is abrogated, and an attack ensues.
Clinical Examples:
- Thyroiditis — autoimmune destruction of the thyroid gland.
- Sympathetic ophthalmia — severe inflammation of a healthy eye following penetrating trauma to the contralateral eye.
- Orchitis — autoimmune inflammation of testicular tissue.
- Encephalitis — autoimmune attack on brain structures.
Modification of Self-Antigens
The essence of this mechanism is that the host's own tissue antigens undergo structural alteration. This modification renders them a novel, unrecognized target for the immune system, which then perceives them as a threat.
The primary causes of such modification include:
- Components of degraded microorganisms
- Fungal components
- Unicellular and multicellular parasites
- Specific metabolites of all the infectious agents listed above
The Phenomenon of Molecular Mimicry
Molecular mimicry underlies cross-reactive immune self-aggression. The mechanism unfolds as follows: a foreign antigen enters the body. In response, the immune system actively produces specific immunoglobulins (Ig). However, these generated Ig molecules cross-react not only with the foreign agent but also with structurally similar host structures.
Examples of Pathologies Involving This Mechanism:
- Autoimmune hemolytic anemias occurring in the setting of leishmaniasis.
- Diffuse glomerulonephritis manifesting after infection with β-hemolytic Streptococcus.
- Enterocolitis in patients infected with pathogenic strains of Escherichia coli.
- Myocarditis developing after a streptococcal infection (pharyngitis, pneumonia, or sinusitis). In this case, the antigenic determinant of the streptococcal M-protein shares strong structural homology with the M-protein located on the cell membrane of host cardiomyocytes.
Principles of Management
The treatment of antigen-dependent autoimmune diseases requires a comprehensive approach. Therapy is built upon a strategic combination of three directions: etiotropic (eliminating the root cause, such as an infectious agent), pathogenetic (interrupting the mechanisms of autoaggression), and symptomatic (relieving clinical manifestations in the patient).