Mutagenic Factors and "Forbidden Clones"
One of the main mechanisms triggering autoaggression is the direct integration of foreign or damaged genetic material into the genome of actively dividing immunocytes. Provoking factors include viral and bacterial DNA fragments, nucleic acid residues from destroyed normal or tumor cells, and specific enzymes—DNA restriction enzymes.
Under their influence, mutations occur, resulting in the formation of "forbidden clones." These are defective populations of T- and B-lymphocytes, as well as antigen-presenting cells. Due to altered perception, they begin to identify normal body antigens as hostile.
- Abnormal T-killers execute direct aggression, physically damaging healthy tissues.
- Plasma cells (mature B-lymphocytes) trigger massive autoantibody production.
Clinical manifestations: various cytopenias (hemolytic anemias, leukopenias, thrombocytopenias, pancytopenias), as well as cytotoxic reactions that often manifest after infection of B-lymphocytes with the lymphotropic Epstein–Barr virus.
Regulatory Cell Imbalance and Loss of Anergy
In a healthy organism, immune tolerance to individual antigenic composition is maintained by a strict dynamic equilibrium between T-helper and T-suppressor cells. In pathology, this ratio breaks down via two possible scenarios:
- A sharp decrease in the number or functional activity of T-suppressors.
- A pathological increase in the number or activity of T-helpers.
The outcome is always the same—intense and uncontrolled proliferation of autoaggressive T-killers and B-lymphocytes. Systemic lupus erythematosus (SLE), multiple sclerosis, and rheumatoid arthritis develop along this pathway.
An additional factor of autoaggression is the abolition of anergy (physiological unresponsiveness) of T-lymphocytes toward self-antigens. This process is triggered when antigen-presenting cells (monocytes and macrophages) begin to secrete excess co-stimulatory factors, such as interleukin-12. This mechanism is especially characteristic of rheumatic diseases.
Global Immune Network Breakdown
A healthy immune system can self-regulate through a complex "idiotype-anti-idiotype" network. In this network, anti-idiotypes act as "supervisors"—essentially autoantibodies directed against self-autoantibodies, controlling their population.
If, under the influence of exogenous or endogenous factors, the level of anti-idiotypic antibodies changes inappropriately (drops or rises), a potent immunostimulatory or immunosuppressive effect occurs. Ideal conditions are created for the synthesis of "forbidden" classes of Ig against the structures of the body's own tissues.
Main causes of network failure:
- T-suppressor deficiency against the background of hereditary or acquired immunodeficiencies.
- Excessive proliferation of T-helpers.
- Nonspecific stimulation of B-lymphocytes (provocateurs: mycoplasmas, Epstein–Barr virus, lipopolysaccharides of gram-negative bacteria).
Examples of diseases: scleroderma, myopathy, immunogenic hemolytic anemias.
Polyclonal Lymphocyte Activation
Certain microbial metabolic products and membrane lipopolysaccharides lack strict antigenic specificity. Entering the internal environment, they act as a nonspecific trigger, simultaneously stimulating multiple distinct clones of T- and B-lymphocytes.
The result of such mass activation is a large-scale lytic effect—lymphocytes begin to chaotically destroy the body's own cells. A prime example of this mechanism is macrophage activation syndrome. It inevitably leads to a severe immunodeficiency state, against which secondary infections rapidly develop, progressing to generalized sepsis.