What Is NK Cell Activity and Why Is It Important?

Natural Killer (NK) cells are a type of white blood cell and a component of the body’s innate immune system. Unlike immune cells such as T-cells, NK cells do not require prior exposure to a pathogen to recognize and eliminate it. This allows them to act as a first line of defense against internal threats. They constantly patrol the body to destroy cells infected with viruses or that have become cancerous.

NK cells make up 5-15% of circulating lymphocytes and are found in the spleen, bone marrow, lymph nodes, and mucosal tissues. This widespread distribution enables them to perform continuous surveillance throughout the body.

The Fundamental Functions of NK Cells

The primary function of NK cells is eliminating abnormal body cells, including those infected by viruses or that have become cancerous. Their ability to attack without prior sensitization makes them rapid responders. They can begin defensive actions within hours of detecting a threat, containing an infection or tumor before the adaptive immune response is mounted.

Beyond direct cell-killing, NK cells help orchestrate the immune response by secreting signaling proteins called cytokines, like interferon-gamma (IFN-γ). These cytokines influence other immune cells, such as macrophages and dendritic cells, recruiting them to the site of an infection or tumor. This communication helps shape the subsequent adaptive immune response.

While classified as part of the innate immune system, some research shows they possess adaptive characteristics, including forming long-lived memory cells. This suggests that NK cells may remember previous encounters with specific pathogens. This memory enables a more robust response upon re-exposure.

Mechanisms of NK Cell Action

NK cell activity is governed by a balance of signals from activating and inhibitory receptors on their surface. These receptors allow NK cells to distinguish between healthy and abnormal cells. Healthy cells display Major Histocompatibility Complex (MHC) class I molecules, which act as a “self” signal that binds to inhibitory receptors, preventing an attack.

A primary activation mechanism is the “missing-self” hypothesis. Virally infected and tumor cells often reduce their MHC class I molecules to evade T-cells. When an NK cell encounters a cell lacking this “self” marker, the absence of an inhibitory signal allows activating signals to dominate, triggering an attack. Stressed cells can also display specific ligands that bind to activating receptors, further promoting a response.

Once an NK cell decides to eliminate a target, it releases cytotoxic granules containing perforin and granzymes. Perforin creates pores in the target cell’s membrane, allowing granzymes to enter and initiate apoptosis, or programmed cell death. NK cells can also induce apoptosis through other pathways and can kill multiple target cells in succession.

Influences on NK Cell Performance

NK cell performance is modulated by various biological and external factors. Cytokines, which are signaling molecules, can enhance or suppress NK cell activity. For example, cytokines like interleukin-2 (IL-2), IL-12, and interferons can boost the cytotoxic capabilities of NK cells, preparing them to combat infections and tumors.

Lifestyle factors also have a considerable influence on NK cell function:

• Chronic stress has been shown to impair NK cell activity.
• Regular physical activity is associated with more robust performance.
• Adequate sleep supports stronger NK cell function.
• A balanced diet provides the necessary resources for immune cell production.

The effectiveness of NK cells also changes over a person’s lifespan and is influenced by genetics. NK cell activity varies with age, and an individual’s genes determine the baseline strength of their response. Chronic viral infections can also alter the function of the NK cell population over time.

The Significance of NK Cell Activity in Human Health

Strong NK cell activity is important for preventing disease, particularly in cancer immunosurveillance. This is the process where the immune system eliminates cancer cells before they form tumors. Because NK cells can kill malignant cells without prior sensitization, they are a first line of defense against cancer, and impaired function is linked to a higher incidence of some cancers.

NK cells are also indispensable for controlling viral infections by eliminating infected cells early, limiting a pathogen’s spread. People with diminished NK cell activity may experience more frequent or severe viral illnesses. The balance of their function is important, as insufficient activity can lead to disease, while over-activation can contribute to autoimmune conditions.

NK cell activity is also relevant in pregnancy. A specific type of NK cell is abundant in the uterus and is involved in the development of the placenta and maintaining a healthy pregnancy. Dysregulation of these uterine NK cells has been associated with complications like infertility and miscarriage.