Natural Killer Cells

What are natural killer cells (NK cells)?

Natural killer cells (NK cells) are white blood cells that destroy infected cells and cancer cells in your body. NK cells are important fighters in your immune system. Your immune system protects you from harmful invaders, like pathogens (viruses, bacteria and parasites) and cancer cells.

NK cells belong to a specific group of white blood cells called lymphocytes, which also includes B-cells and T-cells.

NK cells are called “natural” killers because they can destroy potential threats without prior exposure to a particular pathogen. Other lymphocytes that destroy harmful cells, like cytotoxic T-cells, need previous exposure to a pathogen before they can destroy it.

What do natural killer cells do?

NK cells destroy once healthy cells that now pose a threat. This includes cells infected with viruses and cells that have become malignant (cancer cells). NK cells destroy these harmful cells in the early stages, preventing spread.

Natural killer cells are fighters in your innate immune system, which is an essential part of your immune system. Your innate immune system is your body’s first-line defense against all threats. It includes physical barriers, like skin and mucous membranes, which keep germs out. It includes select immune cells, like NK cells, that destroy threats that have made it past your body’s barriers.

While an NK cell’s primary job is killing, these cells also communicate. They release proteins called cytokines that direct other cells in your immune system to attack harmful cells and pathogens.

How do natural killer cells work in the immune system?

Natural killer cells patrol your body, scanning cells for markers that indicate healthy or diseased cells. If they detect signs a cell is harmful, they release deadly chemicals into the cell to kill it. Whether or not an NK cell kills depends on the signals it does (or doesn’t) receive from the cell it’s scanning (the target cell).

The surface of an NK cell contains multiple receptors that work together to either activate or inhibit (prevent) an NK cell from killing a target.

Inhibition

Natural killer cells don’t attack cells with markers that indicate they’re healthy cells that belong in your body. MHC-1 is the most common cell marker an NK cell recognizes as belonging or “self.” The MHC-1 on the target cell attaches (binds) to an NK cell’s inhibitory receptor. The binding turns the NK cell’s killing function off.

Instead of attacking, the NK cell moves on to the next cell.

Activation

Natural killer cells activate to destroy target cells they don’t recognize as belonging. These include:

• Cells that release activating signals: Cancer cells and infected cells sometimes release chemical signals that cause NK cells to attack.
• Cells with absent or downgraded MHC-1: NK cells will destroy cells that don’t express MHC-1. Sometimes, a cell has MHC-1, but it’s downgraded. This means there’s less of it than is considered normal. For example, a viral infection can downgrade a healthy cell’s expression of MHC-1.

NK cells release perforin and granzymes to kill a target cell. Perforin creates an opening in the target cell so the NK cell can insert granzymes. The granzyme kills the cell.

Activated NK cells release cytokines that tell other white blood cells to help rid your body of the threat.

Where are natural killer cells located?

NK cells start developing in the spongy tissue inside some bones called bone marrow. As they continue to develop, NK cells may stay in your bone marrow. They may move to other tissue and organs in your lymphatic system, such as your:

• Lymph nodes.
• Spleen.
• Tonsils.
• Thymus.

Once they’ve matured, your body releases NK cells into your bloodstream. Mature NK cells also exist in lymph tissue and associated organs. They’re located in organs such as your liver and lungs.

How many natural killer cells are in the human body?

About 5% to 10% of the lymphocytes circulating in your blood are NK cells. They have a short lifespan of about two weeks. At any given time, adults have more than 2 billion NK cells.

What are the conditions and disorders associated with natural killer cells?

Not having enough NK cells leaves you vulnerable to infections and cancer. Research suggests that NK cells may also play an important role in other conditions, including:

• Autoimmune diseases: Problems with how NK cells function may play a role in autoimmune diseases. With autoimmune diseases, immune cells attack your body’s healthy cells — not just diseased or infected cells.
• Asthma: NK cells play a role in your body’s inflammatory response with asthma. NK cells may increase or reduce inflammation, depending on various factors.
• Inflammatory bowel disease (IBD): NK cells play a role in your body’s inflammatory response to bacterial infections in your gut.

What conditions and disorders affect natural killer cells?

Two immunodeficiency conditions are specific to NK cells. Both result from genetic mutations present at birth. A genetic mutation is a change in your DNA, the instructions that tell your cells how to work.

• Classical natural killer cell deficiency (NKD): Involves having no or very few NK cells in your blood. To have classical NKD, less than 1% of your circulating lymphocytes are NK cells.
• Functional natural killer cell deficiency (NKD): Involves having NK cells that don’t function as effectively as normal NK cells.

Both conditions make you more susceptible to infections, including:

• HPV.
• Herpes.
• Cytomegalovirus (CMV).
• Epstein-Barr virus (EBV).
• Varicella-zoster virus (the virus that causes chickenpox).

What is the difference between natural killer cells and cytotoxic T-cells?

NK cells and cytotoxic T-cells are lymphocytes that destroy harmful cells. But they serve different roles in your immune system.

• NK cells can attack any cell that’s a perceived threat. NK cells are part of your innate immune system. Your innate system is your first-line defense against infected and diseased cells. Natural killer cells respond more quickly than T-cells. They begin killing within three days of an infection.
• Cytotoxic T-cells can only attack cells containing pathogens your body has encountered before. It’s part of your adaptive immune system. Your adaptive immune system recognizes specific threats and launches targeted attacks. It takes about a week after an infection for your body to complete the process needed to identify a specific threat and create the particular T-cells required to fight it.

What triggers natural killer cells?

Natural killer cells function based on the signaling processes that involve their activating and inhibitory receptors. They activate when signals that prevent them from attacking (like MHC class I molecules) are absent or downgraded on a target cell.

Do we all have natural killer cells?

Natural killer cells are an essential part of a healthy immune system. Unless you have classical NKD, a genetic condition that prevents your bone marrow from making NK cells, you have NK cells.

A note from Cleveland Clinic

NK cells protect you from infection and diseases by responding to threats quickly. They destroy harmful cells in the early stages, preventing infected cells and cancer cells from spreading. Having a normal amount of healthy NK cells is an important part of a healthy immune system.