Possible pathogenic mechanism of Hashimoto's thyroiditis. Genetically predisposed individuals could be influenced by an environmental trigger (i.e., dietary iodine, infection, pregnancy, cytokine therapy) that induces an autoimmune response against thyroid-specific antigens by infiltrating immune cells. The autoimmune process results in preferential T helper type 1 (T_H1)-mediated immune response and induction of apoptosis of thyroid cells that leads to hypothyroidism.

A scheme of autoimmune events in Hashimoto's thyroiditis. In an initial stage, antigen-presenting cells (APC), mostly dendritic cell and macrophage (Mφ) derived, infiltrate the thyroid gland. The infiltration can be induced by an envinromental triggering factor (dietary iodine, toxins, virus infection, etc.) which causes insult of thyrocytes and releasing of thyroid-specific proteins. These proteins serve as a source of self-antigenic peptides that are presented on the cell surface of APC after processing. Taking up relevant autoantigens, APC travel from the thyroid to the draining lymph node. A central phase occurs in the draining lymph node in which interactions between APC, autoreactive (AR) T cells (that survive as result of dysregulation or breakage of immune tolerance) and B cells result in inducing production of thyroid autoantibodies. In the next step, antigen-producing B lymphocytes, cytotoxic T cells and macrophages infiltrate and accumulate in the thyroid through expansion of lymphocyte clones and propagation of lymphoid tissue within the thyroid gland. This process is preferentially mediated by T helper type 1 (T_H1) cells which secrete regulatory cytokines (interleukin-12, interferon-γ and tumor necrosis factor-α). In a final stage, the generated autoreactive T cells, B cells and antibodies cause massive depletion of thyrocytes via antibody-dependent, cytokine-mediated and apoptotic mechanisms of cytotoxity that leads to hypothyroidism and Hashimoto's disease.