Once tolerance fails, the effector machinery that normally clears pathogens is redirected at self tissue. The damage is not a new mechanism; it is the standard effector repertoire applied to the wrong target.
Autoantibodies cause damage through the same pathways used against microbes. IgG bound to self antigen on a cell surface activates complement, generating C3a and C5a that recruit neutrophils and assembling the membrane attack complex that lyses the cell. The Fc portion of bound IgG engages Fc receptors on macrophages and neutrophils, driving phagocytosis of the opsonized cell or release of lytic enzymes and reactive oxygen species. In Graves disease, an autoantibody against the TSH receptor does not destroy the cell at all — it mimics the ligand and chronically stimulates the thyroid, an example of agonist autoantibody. In myasthenia gravis, anti-acetylcholine receptor antibodies accelerate receptor internalization and activate complement at the neuromuscular junction, reducing signal transmission.
Self-reactive T cells cause damage by direct cytotoxicity and by cytokine-driven inflammation. CD8 cytotoxic T cells recognizing self peptide on MHC class I kill the presenting cell through perforin and granzyme, exactly as they would kill a virus-infected cell. In type 1 diabetes, this destroys insulin-producing beta cells in the pancreatic islets. CD4 helper T cells recognizing self peptide on MHC class II do not usually kill directly; they recruit and activate macrophages and neutrophils, producing the chronic inflammatory infiltrate seen in rheumatoid synovium or multiple sclerosis plaques. The cytokines these cells release — IFN-gamma, TNF, IL-17 — sustain the inflammation and recruit more effectors, so the lesion becomes self-amplifying.
Two features distinguish this from immunodeficiency. First, the damage is antigen-specific and directed at a defined self target, so it produces organ-specific disease rather than broad susceptibility to infection. Second, because the effector arm is intact, the inflammation is active and often chronic, waxing and waning with the availability of the self antigen and the strength of the regulatory brake.