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Figure 7: Proposed model of virus-induced autoimmunity in MG. A “danger signal” (e.g., pathogen infection) stimulates Toll-like receptor-(TLR-) mediated innate immune responses (a), whose dysregulated or persistent activation leads to the chronic inflammation characteristic of MG thymus (b). The chronically established thymic inflammatory state (c), characterized by overexpression of proinflammatory cytokines (e.g., IL-6, IL-10), type I and II IFNs, and T- and B-lymphocyte-attracting chemokines (e.g., CXCR3, RANTES, CXCL13, CCL21), is essential, in the context of a genetically predisposing background, for the establishment of mechanisms (d) contributing to T-cell autosensitization, including presentation or cross-presentation of “self-epitopes” by TECs or myoid cells expressing the autoantigen; upregulation of MHC genes; activation of antigen-presenting cells (APCs); as well as the constant priming of autoreactive T cells, which in turn promote autoimmune response by autoreactive B cells (e). B cell attractants CXCL13 and CCL21 recruit circulating B cells to thymus, including those harboring EBV (a′). EBV infection itself contributes to thymic inflammation (b′). EBV reactivation, influenced by the inflammatory state (c′), results in EBV propagation to uninfected B cells (d′) including AChR-specific B cells (e′). The chronically established inflammation and EBV infection promote the maintenance within the thymus of the autoimmune response (f), which may be thus perpetuated in periphery (g).