Related Experiment Video
Updated: Jun 20, 2026

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity
Published on: August 9, 2017
Natural killer cell cytotoxicity: how do they pull the trigger?
Nicola J Topham1, Eric W Hewitt
1Faculty of Biological Sciences, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
Abstract:
Natural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery.
Insights
Natural killer (NK) cells kill aberrant cells using cytotoxic molecules released from secretory lysosomes. This process, crucial for immune function, involves specialized exocytosis at the immunological synapse.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are crucial immune cells that eliminate aberrant cells, including virally infected and cancerous cells.
- Cytotoxic molecules essential for NK cell killing are stored in specialized secretory lysosomes.
- NK cell-mediated cytotoxicity relies on the targeted release of these molecules via exocytosis.
Purpose of the Study:
- To review recent research on the molecular mechanisms governing NK cell secretory lysosome exocytosis.
- To discuss the immunological consequences of defects in the exocytic machinery of NK cells.
Main Methods:
- This review synthesizes findings from recent studies.
- Focuses on molecular and immunological investigations of NK cell function.
Main Results:
- NK cell killing is mediated by the polarized exocytosis of cytotoxic molecules from secretory lysosomes at the lytic synapse.
- Mutations in exocytic machinery components lead to immune disorders, underscoring the importance of this process.
Conclusions:
- Secretory lysosome exocytosis is fundamental to NK cell cytotoxic function.
- Understanding the molecular basis of this process is vital for addressing related immune disorders.
Related Concept Videos
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
The Extrinsic Apoptotic Pathway
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...

