Natural killer (NK) cell receptors function to regulate the activity of NK cells, determining whether they should kill a target cell or not. These receptors achieve this by integrating activating and inhibitory signals upon encountering other cells.
NK cells are a critical component of the innate immune system, responsible for identifying and eliminating virus-infected cells and tumor cells. This identification process relies on a complex set of receptors expressed on the surface of NK cells. These receptors can be broadly categorized into two types: activating receptors and inhibitory receptors. The balance between the signals received from these two types of receptors dictates the NK cell's response.
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Inhibitory Receptors: These receptors recognize self-MHC (Major Histocompatibility Complex) class I molecules on healthy cells. When an inhibitory receptor binds to MHC I on a target cell, it sends a "don't kill" signal, preventing the NK cell from attacking. This mechanism is important for preventing NK cells from attacking healthy cells. Virus-infected or tumor cells may downregulate MHC I expression to evade T-cell detection. However, this makes them susceptible to NK cell-mediated killing due to the lack of inhibitory signaling.
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Activating Receptors: These receptors recognize stress-induced ligands or altered self-antigens on target cells. When an activating receptor binds to its ligand, it sends a "kill" signal to the NK cell. Activating ligands can include molecules expressed on cells undergoing stress, infection, or malignant transformation.
Integration of Signals:
The decision of an NK cell to kill a target cell is based on the integration of all signals received from both activating and inhibitory receptors.
- If the inhibitory signals outweigh the activating signals: The NK cell will be inhibited and will not kill the target cell.
- If the activating signals outweigh the inhibitory signals: The NK cell will become activated and release cytotoxic granules containing perforin and granzymes, leading to the lysis of the target cell.
In summary, NK cell receptors act as sensors that survey cells for signs of distress or abnormality. They integrate activating and inhibitory signals to determine whether a target cell should be killed, playing a crucial role in immune surveillance and defense against viruses and tumors.
