Pathology of immune-mediated liver injury.

The liver is a special lymphoid organ with its own defense mechanism and it is prone to chronic viral and autoimmune diseases. All constituent liver cells are involved in immune mechanisms against foreign toxins and infectious agents: hepatocytes, Kupffer cells, endothelial cells, hepatic stellate cells and liver resident lymphocytes such as natural killer, natural killer T and dendritic cells. The first line of defense is held up by the innate immune system where the adaptive immune response is more antigen-specific, but needs a longer time to build up. Even in drug injury of the liver, the innate immune system is involved. There is activation of natural killer and natural killer T cells, and liver cell damage is induced mainly by the Fas and FasL pathways. In viral hepatitis, the mechanism of liver injury is mainly immune-mediated since almost none of the hepatitis viruses have turned out to be cytopathic by themselves. Cytotoxic T lymphocytes with CD8 epitopes are the most important effector cell population. The immune defense may be downregulated by regulatory T cell lymphocytes, PD1/PDL-positive lymphocytes or suppressor dendritic cells. In Epstein-Barr virus infection, liver cell injury does not seem to be due to direct antigen-specific CTLs, but the injury is assumingly induced by a bystander reaction from activated lymphocytes in the sinusoids. Autoimmune hepatitis is a paradigm of immune-mediated liver injury and has a special, but not pathognomonic, histopathology. The main effector lymphocytes belong to the CD8 population, which are antigen-specific; however, the mechanisms seem to be suppressed by regulatory T cells.