Question
Natural killer cells
Answer
Natural killer (NK) cells are large granular lymphocytes of the innate immune system, capable of killing virus-infected cells and tumour cells without prior sensitization — unlike cytotoxic T lymphocytes, they do not require antigen-specific priming or MHC-restricted antigen recognition.
Surface markers: characteristically CD3-negative (distinguishing them from T cells) and CD16/CD56-positive.
Mechanisms of target recognition and killing:
- “Missing self” recognition — NK cells carry inhibitory receptors (killer-cell immunoglobulin-like receptors, KIRs) that recognize self MHC class I molecules; normal cells expressing adequate MHC class I deliver an inhibitory signal that prevents NK attack. Virus-infected and many tumour cells often downregulate MHC class I (an immune-evasion strategy against cytotoxic T cells) — this loss of the inhibitory signal (“missing self”) triggers NK-mediated killing.
- Antibody-dependent cellular cytotoxicity (ADCC) — NK cells bear Fc receptors (CD16) that bind the Fc portion of IgG antibody coating a target cell, triggering cytotoxic killing of antibody-coated cells.
- Killing mechanism: release of perforin (forms pores in the target cell membrane) and granzymes (proteases that enter through the pores and trigger apoptosis) — the same effector mechanism used by cytotoxic T lymphocytes.
Immunoregulatory role: NK cells also secrete cytokines, notably IFN-γ, which activates macrophages and helps shape the developing adaptive immune response — providing an early bridge between innate and adaptive immunity, particularly important in early viral infection before an antigen-specific T-cell response has developed.