ABSTRACT
The immune system has a tremendous diversity of mechanisms to protect the body from pathogens. Because the repertoire of specificity expressed by the T and B cell populations is generated randomly, it is bound to include many specific for self-components. Thus, the body must establish self-tolerance to distinguish between self and non-self determinants and avoid autoreactivity. However, all mechanisms have a risk of breakdown. As there are many diverse tolerance-inducing mechanisms, it is likely that there are multiple ways in which tolerance can be broken down, leading to autoimmunity; this may result in organspecific or systemic autoimmune diseases. Organ-specific autoimmune diseases are characterized by the production of autoantibodies and the destruction of specific organs. Primary biliary cirrhosis (PBC) is an idiopathic hepatic disorder characterized by lymphoid infiltrates in the portal tracts of the liver, bile duct destruction, and the presence of disease-specific autoantibodies. The autoantigens recognized in PBC are predominantly components of normal mitochondria, although less common components of the nucleus and cytoplasm are also recognized. Primary biliary cirrhosis has been considered a paradigm for organspecific autoimmune diseases such as Hashimoto’s thyroiditis and type 1 diabetes mellitus. A great deal of attention has been paid to the disease because of the unique immunological abnormalities, particularly the association with high titers of anti-mitochondrial antibodies (AMA) How a mitochondrial antigen sequestered from the immune system by two membrane barriers can elicit an immune response or, once tolerance is broken, how autoimmunity causes tissue damage only in biliary epithelium, remains a mystery. However, the recent advent of molecular biology has provided new approaches to address the pathogenesis of PBC. In this chapter, we will focus mainly on recent data from several areas that have provided a basis for defining the autoimmune response in PBC, and information suggesting an explanation for the selective immune damage.
