Clinical Implications of the Innate and Adaptive Immune Response to HBV and HCV
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GLOBAL PERSPECTIVES: AUSTRALIA (W SIEVERT, SECTION EDITOR)
Clinical Implications of the Innate and Adaptive Immune Response to HBV and HCV Suong T. Le & Kumar Visvanathan
Published online: 22 August 2012 # Springer Science+Business Media, LLC 2012
Abstract The tolerogenicity of the liver renders it vulnerable to hepatotrophic pathogens such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Both viruses have successfully co-evolved within the human host by evading and counteracting immune control. Inadequate cell culture and animal models have limited definitive characterization of the immunological mechanisms arbitrating virus and host co-existence. The clinical sequelae of chronic viral hepatitis such as cirrhosis and hepatocellular carcinoma are not directly mediated by the viruses but rather by hepatotoxic immunological mediators and cytokines. The pro-fibrotic T helper 2 (Th2) response promoted by this altered cytokine milieu is associated with viral persistence. In this chapter, the innate and adaptive immune response to acute and chronic HBV and HCV is reviewed with particular focus on its clinical implications. Keywords Natural killer cells . T lymphocytes . Pattern recognition receptors . TRAIL
S. T. Le Department of Gastroenterology, Southern Health, Clayton Rd, Clayton, Victoria, Australia K. Visvanathan Department of Infectious Diseases, Southern Health, Clayton Rd, Clayton, Victoria, Australia S. T. Le : K. Visvanathan Department of Medicine, Monash University (MMC), Clayton Rd, Clayton, Victoria, Australia K. Visvanathan (*) Department of Infectious Diseases, Monash Medical Centre, Clayton Rd, Clayton, Victoria, Australia 3168 e-mail: [email protected]
Introduction: The Liver Microanatomy and Immunological Constituents The liver represents a unique immunological clearing-house containing a conglomeration of antigenic processing and presentation cells. Compared to the peripheral circulation, the liver is selectively enriched in natural killer (NK) and NKT cells, comprising 30 % of intrahepatic lymphocytes [1]. The fenestrated monolayer of liver sinusoidal endothelial cells (LSEC) facilitates interaction between antigens and circulating lymphocytes [1]. This unique anatomical feature promotes efficient priming and modulation of the adaptive immune response. The LSEC along with Kupffer cells (KC) and dendritic cells (DC), forms a triumvirate of antigen presenting cells crucial for the maintenance of tolerance of the liver under non-inflammatory conditions. TNF-α, IL-10 and TGF-β are important immunomodulatory cytokines constitutively expressed by KC and LSEC, which expedite cross talk between the variable constituents of both the innate and adaptive immune system [1]. The innate immune response attempts to contain viral spread through cytolysis of infected hepatocytes, the creation of a hostile cytokine milieu as well as efficacious recruitment of the adaptive immune response to enable definitive clearance of virus. The viral nucleic acids and secretory proteins are detected by intrace
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