天然杀伤细胞Natural killer cells NK cells是免疫系统的重要组成部分在机体抗病毒和抗肿瘤中发挥重要作用。可自发识别体内异常细胞并通过细胞毒性作用将其迅速清除同时产生各类促炎细胞因子和趋化因子招募和激活其他免疫细胞以启动适应性免疫反应。NK细胞表面具有IL-2中亲和性受体IL-2诱导NK的杀伤活性约需18-24小时。IL-2诱导NK细胞的活性机理尚不清楚可能与增加细胞粘附分
Natural killer cells (NK cells) are an important component of the immune system and play a crucial role in the body's defense against viruses and tumors. They can spontaneously recognize abnormal cells in the body and eliminate them through cytotoxicity. NK cells also produce various pro-inflammatory cytokines and chemokines, recruiting and activating other immune cells to initiate adaptive immune responses.
NK cells express high-affinity receptors for IL-2, and IL-2 induction is required for NK cell cytotoxic activity, which takes about 18-24 hours. The mechanism by which IL-2 induces NK cell activity is not yet fully understood. It may involve increased expression of cell adhesion molecules, enhancing the cytotoxic activity of NK cells against target cells, as well as increasing the expression of granules and serine esterase mRNA in the cytoplasm of NK cells, activating and promoting the killing action of cytotoxic mediators.
TGFβ can inhibit NK cell function and promote their differentiation into ILC1, becoming tissue-resident cells with significantly reduced cytotoxicity. This leads to a weakened ability to kill tumors. Inhibiting TGFβ in the tumor microenvironment is an important strategy for restoring NK cell function.
CD69 is an activation marker for NK cells. It forms dimers and is expressed on the surface of activated T cells, B cells, NK cells, neutrophils, and platelets. It is a type II membrane glycoprotein associated with the activation of the natural killer cell antigen family. CD69 plays a critical role in NK cell function and helps maintain NK cell activation.
The basic principle of using flow cytometry with CD107a as a marker to detect NK cell activity is that NK cells contain a large amount of granules with cell lytic activity. After activation, NK cells release these granules into target cells through immune synapses. These granules include cell lytic proteins perforin and granulysin, among which granulysin is expressed on the membrane and is also known as lysosome-associated membrane protein 1 (LAMP1) or CD107a. NK cell cytotoxic activity leads to the translocation of CD107a molecules to the cell membrane, and the expression level of CD107a is significantly correlated with NK cell cytotoxic activity. Therefore, NK cells positive for CD107a expression represent NK cells with cytotoxic activity.
Granzyme B (GrB) is present in the granules of NK cells and cytotoxic T cells. GrB is essential for the rapid induction of target cell death through apoptosis (interaction with cytotoxic T cells). GrB activates a cascade of intracellular caspases and ultimately leads to target cell killing
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