Natural Killer Cells: How They Destroy Infected & Cancerous Cells

NK Cell Cytotoxic Mechanisms

Natural killer (NK) cells are innate lymphocytes that eliminate virus‑infected and transformed cells without prior sensitization.

1. Direct Cytotoxicity

• Activating receptors (NKG2D, NCRs) detect stress ligands on target.
• Inhibitory receptors (KIRs, CD94/NKG2A) sense self‑MHC‑I; loss of MHC‑I (“missing self”) triggers killing.
• Lytic granules → perforin pores → granzyme entry → caspase‑dependent apoptosis.

2. Antibody‑Dependent Cellular Cytotoxicity (ADCC)

CD16 (FcγRIIIa) binds IgG‑opsonized targets → same granule exocytosis.

3. Death Receptor Pathways

• FasL–Fas, TRAIL–DR4/5 interactions → extrinsic apoptosis.

4. Cytokine Production

IFN‑γ, TNF‑α, GM‑CSF → activate macrophages, enhance Th1 response, upregulate MHC on targets.

5. Crosstalk

NK–DC interaction shapes adaptive immunity; NK cells edit DC repertoire.

Clinical Relevance

• Haploidentical HSCT: donor NK alloreactivity reduces relapse/GVHD.
• CAR‑NK, cytokine‑armed NK in clinical trials for solid tumors.