How do natural killer cells detect virally infected cells and mediate cytotoxicity?

How do natural killer cells detect virally infected cells and mediate cytotoxicity?

• A. By recognizing increased MHC I expression
• B. By recognizing decreased MHC I expression and inducing apoptosis via perforin/granzyme
• C. By phagocytosing infected cells
• D. By producing antibodies against infected cells

Answer: (B)

Natural killer cells patrol for cells with signs of stress or infection by sensing the absence of normal self markers, particularly MHC class I molecules. When a virally infected cell downregulates MHC I to evade CD8+ T cells, inhibitory signals on NK cells decline and activating signals prevail, tipping the balance toward activation. Once activated, NK cells unleash cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and activate caspases, driving the target cell to apoptosis. This allows rapid elimination of infected cells without requiring antigen presentation on MHC I. NK cells can also kill via antibody-dependent mechanisms when antibodies coat targets, but the described action is the recognition of decreased MHC I with perforin/granzyme–mediated apoptosis.

Natural killer cells patrol for cells with signs of stress or infection by sensing the absence of normal self markers, particularly MHC class I molecules. When a virally infected cell downregulates MHC I to evade CD8+ T cells, inhibitory signals on NK cells decline and activating signals prevail, tipping the balance toward activation. Once activated, NK cells unleash cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and activate caspases, driving the target cell to apoptosis. This allows rapid elimination of infected cells without requiring antigen presentation on MHC I. NK cells can also kill via antibody-dependent mechanisms when antibodies coat targets, but the described action is the recognition of decreased MHC I with perforin/granzyme–mediated apoptosis.