Learning Objectives
Master the Major Functions of Natural Killer (NK) Cells. Understand their unique role as innate lymphocytes, their mechanisms of apoptosis induction (perforin/granzymes), the “missing self” hypothesis regarding MHC I, and the process of Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) for the USMLE Step 1.
1. General Characteristics
Natural Killer cells are unique lymphocytes that belong to the Innate Immune System. Unlike B and T cells, they do not require prior sensitization or MHC-specific antigen presentation to act.
| Feature | Description |
|---|---|
| Origin | Lymphoid lineage (related to B and T cells). |
| Primary Targets | Virally infected cells and tumor cells. |
| Cytokine Enhancement | Activity is strongly enhanced by IL-2, IL-12, IFN- , and IFN- . |
2. Mechanism of Induced Apoptosis
NK cells utilize a balance of stimulatory and inhibitory signals to decide whether to kill a target cell.
| Mechanism | How it Works |
|---|---|
| The “Missing Self” Rule | NK cells look for MHC I. If MHC I is absent (a common tactic by viruses and tumors to hide from CD8+ cells), the inhibitory signal is lost, and the NK cell kills. |
| Perforin & Granzymes | NK cells release Perforin (creates holes in the target membrane) and Granzymes (proteases that enter the holes to trigger the caspase cascade/apoptosis). |
IFN- Production |
Once activated, NK cells produce IFN-, which acts as a powerful signal for Macrophage activation. |
Activity:
3. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
NK cells can also target cells that have been “marked” by the adaptive immune system using antibodies.
| Component | Role in ADCC |
|---|---|
| CD16 | The surface receptor on NK cells that binds the Fc region of IgG. |
| IgG | The specific antibody that binds to antigens on the target cell surface acts as a bridge for the NK cell. |
| Outcome | Activation of the NK cell leads to the immediate release of cytotoxic granules into the target cell. |
Activity:
High-Yield Clinical Pearls:
- CD16 vs CD56: These are the two classic markers for NK cells. CD16 is used for ADCC, while CD56 is the unique identifier (though its function is less clear in Step 1).
- Viral Evasion: Viruses often downregulate MHC I to avoid CD8+ T cells. This makes them more vulnerable to NK cells, creating a “no-win” situation for the pathogen.
- Chediak-Higashi Syndrome: This immunodeficiency involves a defect in lysosomal trafficking, which results in impaired NK cell function and recurrent pyogenic infections.