Semin Liver Dis 2014; 34(03): 297-317
DOI: 10.1055/s-0034-1383729
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Breach of Tolerance: Primary Biliary Cirrhosis

Lifeng Wang
1   Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
,
Fu-Sheng Wang
1   Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
,
Christopher Chang
2   Division of Allergy and Immunology, Department of Pediatrics, Thomas Jefferson University, Nemours/A.I. duPont Hospital for Children, Wilmington, Delaware
,
M. Eric Gershwin
3   Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, California
› Author Affiliations
Further Information

Publication History

Publication Date:
24 July 2014 (online)

Abstract

In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a “liver tolerance effect,” and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play important roles in breach of tolerance in the development of PBC.