Читать книгу Autoimmune Liver Disease - Группа авторов - Страница 31

Hepatocytes can die because of either necrosis or apoptosis. Necrosis is the loss of plasma membrane integrity with release of the cellular contents locally, which triggers an inflammatory response. Apoptosis is a highly regulated process in which cells that are damaged, senescent or deregulated self‐destruct with a lower release of inflammatory products. Dying cells undergo morphologic modifications including chromatin condensation, nuclear fragmentation, and generation of apoptotic bodies. Furthermore, they express signals on the cell surface that allow macrophage recognition. Apoptosis is essential to avoid the outflow of intracellular contents and to limit the immunologic response against intracellular autoantigens. Nevertheless, apoptotic bodies and fragments can under some circumstances constitute a major source of immunogens in autoimmune diseases that involve the targeting of ubiquitous autoantigens. This has been described in PBC. In the BECs of patients with PBC there is increased DNA fragmentation, implying increased apoptosis, when compared with normal controls. While mitochondrial proteins are present in all nucleated cells, in PBC there is a highly specific multilineage immune response directed to the nominal mitochondrial autoantigenic epitope, the inner lipoyl domain of the E2 subunit of the pyruvate dehydrogenase complex (PDC‐E2) of the BECs. Apoptosis of BECs has been proposed as a potential source of “neoantigens” that could be responsible for activation of autoreactive T lymphocytes or a target for effector cells or antibodies. PDC‐E2 is not only immunologically intact during apoptosis in BECs, but it localizes in the apoptotic bodies of BECs where it is accessible to recognition by anti‐mitochondrial antibodies.