» 自然杀伤(NK)细胞毒性

自然杀伤(NK)细胞毒性

1975
  • Rolf Kiessling
  • Eva Klein
  • Hans Wigzell
Natural Killer cells in a laboratory setting, examining cytotoxicity mechanisms.

Natural Killer (NK) cells are cytotoxic lymphocytes of the innate immune system, critical for early defense against viral infections and cancer. Unlike T cells, they do not require prior sensitization. NK cells identify and kill target cells that have downregulated MHC class I molecules—a common immune evasion tactic by tumors and viruses—through a “missing-self” recognition mechanism, inducing apoptosis via perforin and granzymes.

Natural Killer (NK) cells provide a rapid, first-line defense against cellular threats. Their function is governed by a balance of signals from activating and inhibitory receptors on their surface. Healthy cells express MHC class I molecules, which are recognized by inhibitory receptors on NK cells (like KIRs and NKG2A). This interaction sends a strong “don’t kill me” signal, preventing the NK cell from attacking. This is known as “missing-self” recognition: the absence of the ‘self’ MHC class I signal is what triggers the attack.

When a cell becomes cancerous or is infected by certain viruses, it often reduces the expression of MHC class I molecules to evade detection by cytotoxic T cells. This, however, makes it a prime target for NK cells. The lack of an inhibitory signal, often coupled with the presence of stress-induced ligands recognized by activating NK cell receptors (like NKG2D), tips the balance towards activation. Once activated, the NK cell’s cytotoxic mechanism is very similar to that of a CTL. It releases perforin and granzymes to induce apoptosis in the target cell. NK cells can also induce cell death through other pathways, such as the Fas/FasL interaction, and are key players in antibody-dependent cell-mediated cytotoxicity (ADCC), where they kill target cells coated with antibodies.

UNESCO Nomenclature: 2415
– Immunology

类型

Biological Mechanism

Disruption

Substantial

使用方法

Widespread Use

Precursors

  • 先天免疫和适应性免疫的区别
  • 确定淋巴细胞为关键免疫细胞
  • 干扰素的发现及其在抗病毒防御中的作用
  • 体外细胞杀伤试验的开发
  • 了解肿瘤免疫逃避机制

应用

  • 基于NK细胞的癌症免疫疗法
  • 病毒感染的治疗方法
  • 监测患者的免疫状态
  • 了解妊娠免疫学(子宫内 NK 细胞丰富)
  • 抗体依赖性细胞介导细胞毒作用(ADCC)药物的开发

专利:

NA

Potential Innovations Ideas

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Related to: natural killer cell, NK cell, innate immunity, missing-self recognition, MHC class I, immunology, cancer surveillance, perforin, granzyme, ADCC.

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