NK (Natural Killer) cells are primarily activated by α/β interferons (IFNs) or interleukin-12 (IL-12).
Here's a more detailed breakdown:
How NK Cells Become Activated
NK cells, a key component of the innate immune system, play a crucial role in identifying and eliminating infected or cancerous cells. Unlike T cells, they don't require prior sensitization to an antigen. Their activation is triggered by a complex interplay of activating and inhibitory signals.
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Cytokine Activation:
- Interferons (IFNs): Type I interferons (α and β) are potent activators of NK cells. These cytokines are produced by cells infected with viruses. The binding of IFN-α/β to their receptors on NK cells leads to increased cytotoxicity and proliferation.
- Interleukin-12 (IL-12): IL-12, produced by macrophages and dendritic cells, is another key cytokine that stimulates NK cell activity. It enhances the cytotoxic function of NK cells and promotes the production of interferon-gamma (IFN-γ).
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Balance of Activating and Inhibitory Signals: NK cells express a variety of activating and inhibitory receptors. The overall activity of an NK cell is determined by the balance between these signals.
- Activating Receptors: These receptors recognize ligands expressed on target cells, such as cells under stress, infected cells, or tumor cells. Engagement of activating receptors triggers NK cell cytotoxicity. Examples include NKG2D and certain killer cell immunoglobulin-like receptors (KIRs).
- Inhibitory Receptors: These receptors recognize MHC class I molecules, which are present on healthy cells. This interaction delivers an inhibitory signal, preventing NK cell activation and protecting healthy cells from being attacked. KIRs are a major class of inhibitory receptors. When a cell lacks MHC class I (a common strategy employed by viruses or tumor cells to evade T cell responses), the inhibitory signal is absent, and the activating signals dominate, leading to NK cell activation.
The Role of NK Cells in Immunity
NK cells contribute to the early immune response by:
- Killing infected or cancerous cells: This is achieved through the release of cytotoxic granules containing perforin and granzymes, which induce apoptosis (programmed cell death) in the target cells.
- Producing cytokines: NK cells produce IFN-γ, which activates macrophages and enhances the adaptive immune response.
In essence, NK cell activation represents a critical innate immune mechanism, rapidly responding to threats based on the integration of stimulatory cytokine signals and a sophisticated assessment of target cell surface markers.
