natural killer cell mediated cytotoxicity

Definition

Target type: biologicalprocess

The directed killing of a target cell by a natural killer cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors. [GOC:add, GOC:pr]

Natural killer (NK) cell-mediated cytotoxicity is a crucial component of the innate immune system, providing rapid defense against infected and cancerous cells. It involves a series of intricate steps orchestrated by NK cells, specialized lymphocytes that patrol the body for aberrant cells.

**1. Recognition and Activation:**
- NK cells express a diverse array of receptors on their surface, including activating and inhibitory receptors.
- Activating receptors recognize stress-induced molecules (e.g., MHC class I downregulation, NKG2D ligands) expressed by target cells, triggering NK cell activation.
- Inhibitory receptors bind to MHC class I molecules present on healthy cells, delivering an inhibitory signal that prevents NK cell activation.
- The balance between activating and inhibitory signals determines the fate of the target cell.

**2. Cytokine Production:**
- Upon activation, NK cells release a variety of cytokines, including interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF).
- These cytokines amplify the immune response by activating other immune cells and promoting inflammation.

**3. Granule Exocytosis:**
- NK cells contain cytotoxic granules filled with proteins, such as perforin and granzyme B.
- Upon binding to the target cell, NK cells release these granules via exocytosis.
- Perforin creates pores in the target cell membrane, allowing granzyme B to enter.

**4. Target Cell Apoptosis:**
- Granzyme B is a serine protease that activates the caspase cascade within the target cell, leading to programmed cell death (apoptosis).
- The target cell undergoes a series of morphological changes, including DNA fragmentation and nuclear condensation, ultimately resulting in its demise.

**5. Clearance of Debris:**
- The apoptotic target cell is engulfed and cleared by macrophages, preventing the release of harmful intracellular contents.

**In Summary:** NK cell-mediated cytotoxicity is a tightly regulated process that relies on a complex interplay of receptors, cytokines, and cytotoxic molecules. By eliminating infected and cancerous cells, NK cells play a vital role in maintaining immune homeostasis and protecting the host from disease.'
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Proteins (9)

Compounds (126)