Microbiology, 2021

706 17 • Innate Nonspecific Host Defenses
Figure 17.16
Natural killer (NK) cells are inhibited by the presence of the major histocompatibility cell (MHC) receptor on healthy cells.
Cancer cells and virus-infected cells have reduced expression of MHC and increased expression of activating molecules. When a NK cell
recognizes decreased MHC and increased activating molecules, it will kill the abnormal cell.
Once a cell has been recognized as a target, the NK cell can use several different mechanisms to kill its target.
For example, it may express cytotoxic membrane proteins and cytokines that stimulate the target cell to
undergo apoptosis, or controlled cell suicide. NK cells may also use perforin-mediated cytotoxicity to induce
apoptosis in target cells. This mechanism relies on two toxins released from granules in the cytoplasm of the
NK cell: perforin, a protein that creates pores in the target cell, and granzymes, proteases that enter through
the pores into the target cell’s cytoplasm, where they trigger a cascade of protein activation that leads to
apoptosis. The NK cell binds to the abnormal target cell, releases its destructive payload, and detaches from
the target cell. While the target cell undergoes apoptosis, the NK cell synthesizes more perforin and proteases
to use on its next target.
NK cells contain these toxic compounds in granules in their cytoplasm. When stained, the granules are
azurophilic and can be visualized under a light microscope (Figure 17.17). Even though they have granules, NK
cells are not considered granulocytes because their granules are far less numerous than those found in true
granulocytes. Furthermore, NK cells have a different lineage than granulocytes, arising from lymphoid rather
than myeloid stem cells (Figure 17.12).
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