Pathogenesis of autoimmune hepatitis

Autoimmune hepatitis is initiated by CD4 T cells that recognize self-antigen. The effector cells differentiate into functional phenotypes according to cytokines in the microenvironment and the nature of the triggering antigen. Hepatocytes can express class II molecules and present antigenic peptides through a bystander mechanism. NKT cells reside in the normal liver but may be involved in liver cell damage possibly through the expression of Fas ligand. Autoantibodies may also participate in the process by complexing with antigen on the hepatocyte membrane surface and by interacting with mononuclear cells with Fc receptors. Molecular mimicry generates cross-reactivities that predispose the immune system to cross-react with self-antigens. Multiple exposures to pathogens with antigenic similarities may prime a cross-reactive subset of T cells in the genetically predisposed host. Autoimmunity against one self-antigen may then spread through molecular mimicry to other homologous self-antigens and may lead to overt autoimmune disease. Anatomically distant tissues may also become involved as autoreactive T cells that had been activated in one organ expand and infiltrate other organs that express similar epitopes.