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Autoimmunity occurs when the immune system attacks its own tissues due to failure of tolerance mechanisms. Central (thymic) tolerance eliminates T cells with high affinity for autoantigens through clonal deletion: the sigmoidal curve of P_deletion versus affinity defines an Af_thresh threshold that separates tolerized clones from those that escape. Peripheral tolerance (mediated by Treg cells, CTLA-4, PD-1) suppresses autoreactive clones that escaped to the thymus.

The Treg/Teff balance is the key quantitative determinant of autoimmunity: when R_Treg < 0.1, autoreactive clones proliferate unchecked. Diseases such as rheumatoid arthritis (RA), lupus (SLE), and type 1 diabetes show reduced R_Treg in target organs. Tissue-specific Treg cells are the main mechanism of in situ suppression.

Autoantibodies produce tissue damage by three mechanisms: (1) deposition of immune complexes (ICs) that activate complement (lupus nephritis, vasculitis), modeled as a kinetic deposition process; (2) complement-dependent cytotoxicity (AIHA, PTI); (3) functional blockade of receptors (myasthenia gravis: anti-AChR, Graves' hyperthyroidism: anti-TSHR). Amplification of the complement cascade (C3a, C5a) generates intense local inflammation.

In rheumatoid arthritis, the IL-23/Th17/IL-17 axis is the central proinflammatory circuit: IL-23 expands Th17 lymphocytes that produce IL-17, which in turn stimulates synoviocytes and osteoclasts destruction of cartilage and bone. Anti-IL-17 (secukinumab) or anti-IL-23 (ustekinumab) biologics interrupt this circuit. Hill's kinetic model describes the inhibition: [biological] >> EC almost complete suppression of IL-17.

Treatment of autoimmunity with immunosuppressants (methotrexate, glucocorticoids) globally suppresses the immune response, reducing k_act and k_Th17. Biologics act on specific targets. The risk is the excessive shift of the balance towards immunosuppression: the model predicts that too high R_Treg (> 0.8) is associated with a higher risk of opportunistic infections and certain tumors (reduced immunosurveillance).

>Model

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