What are Natural Killer (NK) Cells?
Natural Killer (NK) cells are a specialized type of white blood cell, or lymphocyte, crucial for the innate immune system. They develop mainly in the bone marrow from hematopoietic stem cells. Unlike T-cells and B-cells of the adaptive immune system, NK cells don't need prior activation to recognize threats, making them immediate responders. They are constantly circulating and ready to eliminate compromised cells, hence the name "Natural Killer".
The Mechanisms of NK Cell Activation
NK cells distinguish healthy from abnormal cells using a balance of activating and inhibitory receptor signals.
The Missing-Self Hypothesis
Healthy cells express MHC class I proteins. NK cells have inhibitory receptors that bind to these, signaling 'self'. Virus-infected or tumor cells often reduce MHC I expression, removing the inhibitory signal and allowing the NK cell to attack.
The Induced-Self Recognition
Stressed cells, like those infected or cancerous, can express ligands that bind to NK cell activating receptors (like NKG2D binding MICA/B or ULBPs). This activating signal can override inhibitory signals.
The Killing Process: How NK Cells Eliminate Targets
Upon activation, NK cells form an immunological synapse with the target cell and use various methods to kill it.
- Granule Exocytosis: NK cells release perforin and granzymes. Perforin creates pores in the target cell, letting granzymes enter and trigger programmed cell death (apoptosis).
- Death Receptor Pathway: They can induce apoptosis by binding to death receptors on the target cell via molecules like Fas Ligand and TRAIL.
- Cytokine and Chemokine Production: Activated NK cells release signals like IFNγ and TNF-alpha, which boost their activity and recruit other immune cells.
The Promising Field of NK Cell Therapy
NK cells are promising for immunotherapy, especially in cancer treatment. Research focuses on enhancing their function through:
- Adoptive NK Cell Transfer: Growing NK cells outside the body and reintroducing them.
- CAR-NK Therapy: Genetically modifying NK cells to target specific cancer cells.
- NK Cell Engagers: Molecules that link NK cells to tumor cells to boost killing.
Learn more about NK cells in immunotherapy in this Nature journal review: Nature: Roles of natural killer cells in immunity to cancer, and approaches to harness their function.
Natural Killer Cells vs. T Cells: Key Differences
NK cells and T cells are both lymphocytes but differ in function. A comparison table highlights these differences.
| Feature | Natural Killer (NK) Cells | T Cells |
|---|---|---|
| Immune System | Innate (Rapid Response) | Adaptive (Targeted Response) |
| Activation | No prior activation required | Requires activation by specific antigens |
| Target Recognition | Recognize stress signals (missing/induced self) | Recognize specific antigens presented by MHC |
| Speed of Response | Very rapid, immediate action | Slower; requires initial priming and memory formation |
| Specificity | Non-specific; attacks any stressed cells | Highly specific to a single antigen |
| Immunological Memory | Innate memory exists (less understood) | Strong, long-term memory for specific antigens |
| Self-Tolerance | Regulated by inhibitory signals from MHC I | Regulated by central and peripheral tolerance |
Subsets of NK Cells
Human NK cells have subsets, often based on CD56 expression:
- CD56bright NK cells: Found more in tissues, they are good at producing cytokines but less cytotoxic.
- CD56dim NK cells: The majority in blood, they are highly cytotoxic killers, vital for removing infected or cancerous cells.
Conclusion
In medical terms, NK signifies Natural Killer cells, vital components of the innate immune system. They provide rapid defense against viruses and cancer by identifying and destroying abnormal cells without prior sensitization, making them a key focus in immunotherapy research.
