Genetic defects affecting lymphocyte cytotoxicity

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• 作者：Alain Fischer ; Sylvain Latour ; Geneviè ; ve de Saint Basile
• 刊名：Current Opinion in Immunology
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：19
• 期：3
• 页码：348-353
• 全文大小：188 K

文摘

Cytolytic lymphocytes kill virus-infected cells as well as tumor cells by the exocytosis of the content of specialized secretory lysosomes at the immunological synapse (IS). Perforin and granzymes are the molecular effectors that induce rapid target cell death. Cytolytic T cells are activated by specific antigen recognition whereas the cytolytic activity of natural killer cells is initiated by specific activating receptors or combinations thereof and is inhibited by self MHC class I recognition. The cytolytic process has received considerable attention and can now be described as a multi-step process including cell activation, polarization of specialized lysosomes — lytic granules — toward the IS, tethering of the lytic granules to the plasma membrane, priming for fusion with the plasma membrane, effective fusion and release of granule content in the IS cleft, and death of the target. This is a highly flexible system that could enable a cytolytic cell to subsequently kill target cells bound at different sites around the effector cell. Cytolytic cells exert a second effector function consisting of the secretion of cytokines, notably interferon γ. The latter secretory process functions independently from the exocytic pathway of the lytic granules.