Chapter Twenty-Six - Natural killer cells in the liver

Abstract

The liver is comprised of both parenchymal cells (hepatocytes) and nonparenchymal cells. Hepatocytes occupy 80% of the liver volume and fulfil the needs of metabolism, toxin degradation and various protein syntheses. Nonparenchymal cells include endothelial cells, hepatic stellate cells (HpSCs), Kupffer cells, dendritic cells (DCs) and lymphocytes. The liver is the largest solid organ in the body and has dual blood supplies: hepatic artery and portal vein. The portal vein transports nutrients and substances absorbed from the gastrointestinal system into the liver. This renders the liver continuously exposed to bacterial products, toxins and food antigens from the gut. Innate immunity in the liver represents a first line of defence, which consists of humoral factors, phagocytic cells and lymphocytes. These innate components can directly kill or help to kill pathogens, usually in a nonspecific manner. The liver collects gut-derived blood rich in pathogens, bacterial products, toxins and food antigens. To protect the host from pathogenic infection while maintaining a low profile response to antigens from food and gut commensals, the liver maintains a unique repertoire of immune cells, which is particularly rich in natural killer (NK) cells. NK cells play an important role in the regulation of innate immunity and form the first line of defence through a variety of mechanisms, including the release of perforin, granzymes and cytokines, and inducing target cell apoptosis. Many innate immunity components, including liver NK cells, act through recognizing pattern-recognition receptors, the specific structures expressed on invaded pathogens. In addition, liver NK cells may also play a role in preventing cancer, fibrosis, liver regeneration and regulating immune responses.