Learning Objective: Understand the major functions, activation signals, and mechanisms of natural killer (NK) cells in innate immunity, and their role in immune defense.
- Lymphocyte of the innate immune system.
- Recognizes and kills virally infected cells and tumor cells without prior sensitization.
- Bridges innate and adaptive immunity via cytokine production.
Major Functions
| Function | Mechanism | Clinical Relevance |
|---|---|---|
| Direct cytotoxicity | Release of perforin and granzymes → apoptosis of target cells | Eliminates virally infected and malignant cells |
| Activation of macrophages | Produce IFN-γ → enhances macrophage microbicidal activity | Key in intracellular pathogen defense |
| Antibody-dependent cell-mediated cytotoxicity (ADCC) | CD16 binds Fc portion of IgG → NK cell activation and target lysis | Important in therapeutic monoclonal antibody therapy |
| Regulated killing | Triggered by absence of MHC I or nonspecific activation signals | Tumor immune surveillance |
Activation Signals
- Cytokines enhancing activity: IL-2, IL-12, IFN-α, IFN-β
- Inhibitory signals: Presence of MHC I on healthy cells prevents NK killing
Key Point: NK cells balance activating and inhibitory signals to target abnormal cells while sparing healthy cells.
Key Points for USMLE Step 1
- NK cells are part of the innate, not adaptive, immune system.
- Kill via perforin/granzyme pathway or ADCC.
- IL-2, IL-12, IFN-α/β enhance activation.
- Recognize abnormal cells by missing self (MHC I absent).
- Produce IFN-γ to activate macrophages.
