系统生物学在免疫系统研究中的应用

Macrophages are found throughout the human body Several decades of intensive study have revealed thousands of proteins that play important roles in the encounters between the immune system and pathogenic organisms. With the volumes of genomic information (both human and microbial) that are rapidly becoming available and the development of high-throughput analysis of mRNA and protein expression, protein modifications and protein-protein interactions, the field is at a turning point where major advances are likely to come from studies into how a multitude of proteins in many pathways interact with each other to coordinate our defense against infection. The innate immune system also initiates local and sometimes systemic inflammatory responses that alert the body to the presence of potential threats and guides the development of subsequent adaptive immune responses that evolve in the weeks following infection. The inflammatory process is a double-edged sword; while on one hand inflammation is usually helpful and protective, it sometimes can become deregulated and result in tissue destruction and physiological changes that endanger the health of a person. Septic shock, a life-threatening systemic inflammatory response to bacterial infection, is a major problem in hospitals around the world, and inflammatory processes cause damage in a broad range of diseases including atherosclerosis, arthritis, and cancer. Phagocytes such as macrophages, neutrophils, dendritic cells and monocytes are central effector cells of the innate immune system (see box). These cells constantly survey the body and recognize, internalize, kill and degrade foreign microbes. These cells also secrete inflammatory chemokines and cytokines and process antigens that train the adaptive immune response. The Aderem laboratory is focused on understanding the molecular and genetic factors that regulate these functions of phagocytes. How do macrophages detect microbes and identify infectious agents? A remarkable feature of the innate immune system is its capacity to recognize so many different types of microbes. Phagocytes use receptors belonging to several different genes families to bind microbes (see Figure 1 and Figure 2).These receptors permit the phagocyte to engulf and destroy the microbes. Some of the receptors are involved in the uptake/engulfment process, and others are involved in initiating the signals that announce to the immune system that microbes have been encountered. How do immune cells internalize and kill microbes? Phagocytosis is an ancient process by which phagocytes such as monocytes, macrophages, neutrophils and dendritic cells internalize large particles like bacteria or fungi and kill them. After recognition of a particle as foreign and potentially dangerous, signals are delivered into the phagocyte that cause reorganization of the actin cytoskeleton and recruitment and extrusion of membrane leading ultimately to complete enclosure of the particle within the phagocytes membranes. This newly formed compartment in the cell then matures into an acidic compartment where enzymes cause death and degradation of the potentially harmful organism. In addition to the central importance of phagocytosis to defense, internalization of dead cells and debris is also an important role of phagocytes in normal tissue maintenance and wound healing. Immunity Links: Aderem Lab Immunity Diseases Infectious Diseases Disease in the Developing World Autoimmunity and Inflammation Diabetes Heart Disease Cancer

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