The immunological milieu of the liver

From the immunology standpoint, the liver is a peculiar organ for several reasons that range from its anatomical location to its cytoarchitecture and its variety of specific functions. Receiving blood directly from the digestive system, the liver is the crossroad at which the majority of antigens enter the organism. Hence, the milieu of the liver must provide a finely tuned balance between generating tolerance to self as well as to nonpathogenic molecules and microorganisms and producing an appropriate immune response to pathogens. Knowledge of the mechanisms that effectively maintain this balance is critical to the understanding of the pathogenesis of chronic inflammatory liver diseases, infectious, autoimmune, and others. Several theories have been proposed to explain what causes one or another response to take precedence. Although no definitive answer is yet available, the critical elements include, for tolerance, the particular cytoarchitectural features and the intrahepatic existence of antigen-presenting cells and, for immunity, inflammatory expressions including type 1 cytokines and chemokines, notably CCR5. Herein we review the available data on immune responses in the liver with particular emphasis on the unique structural and functional features of this "lymphoid" organ.