Natural Killer Cells

Natural killer cells are lymphocytes belonging to the same family as B cells and T cells. They are cytotoxic cells of the innate immune system and circulate in the body seeking out infected and cancerous cells. When they encounter an abnormal cell, natural killer cells secrete cytotoxic granules to destroy the cell and limit the spread of infection or disease in the body.

What Are Natural Killer Cells?

Natural killer cells (NK cells) are lymphocytes of the innate immune system. These white blood cells belong to the same family as B cells and T cells and play an important role in limiting the spread of infection. When a NK cell encounters a cancer cell or an infected host cell, it secretes cytotoxic granules in response to signals from the infected cell. The granules contain perforin and granzymes, which work together to stimulate apoptosis of the infected cell.

Where Are Natural Killer Cells Found?

Natural killer cells are immune sentinels that roam the body seeking out infected and cancerous cells. For this reason, NK cells are widespread throughout the body and are found in most human tissues. They are found in their highest concentrations in the bloodstream, the uterus, the lungs, and the liver.

Origin of Natural Killer Cells

Natural killer cells develop from stem cells in the bone marrow, lymph nodes, the spleen, or the tonsils. Mature NK cells account for around 5-20% of circulating white blood cells in the human body.

Function of Natural Killer Cells

Natural killer cells are named because they are ‘naturally’ cytotoxic, meaning that (unlike cytotoxic T cells) they do not require antigen exposure to become activated. Their key function is to limit the spread of infection in the body by destroying infected host cells and to locate and kill cancer cells.

NK Cells vs. Viral Infection

Natural killer cells are cytotoxic cells that defend the body against viral infections. When they encounter a virus-infected host cell, NK cells release cytotoxic granules that contain perforins and granzymes. Perforins are proteins that form pores in the cell membrane of the target cell. Granzymes are enzymes that enter the target cell via the holes created by the perforins. Once inside the infected cell, the granzymes initiate apoptosis (programmed cell death), and the virus dies along with the host cell.

This mechanism of inducing cell death keeps viral agents contained within the host cell and therefore limits their spread to other parts of the body. If NK cells only used perforins against target cells, the virus could escape and infect other cells.

NK cells contain and limit the spread of viral infections while the adaptive immune system generates antigen-specific cytotoxic T cells. Once activated, the cytotoxic T cells will get to work clearing the infection from the body.

NK Cells vs. Cancer cells

NK cells also attack and destroy cancerous cells in the body. They handle cancer cells in the same way they deal with virus-infected cells; by releasing cytotoxic granules containing perforin and granzyme. The perforin creates holes in the cell membrane of the cancer cell, and the granzymes enter the cell through these pores. The granzymes then initiate apoptosis by activating apoptotic enzymes called caspases, leading to cell death.

Regulation of Natural Killer Cells

As they roam the tissues of the body, natural killer cells constantly encounter other cells. Infected or otherwise abnormal cells will trigger the NK cells to release cytotoxic granules, but they will not kill healthy ‘self’ cells. NK cells ‘know’ which cells are healthy and which are infected thanks to molecules that are expressed on their surface.

Infected and cancerous cells express certain molecules on their surface, which are recognized by activation receptors on the surface of NK cells. When the activation receptor binds to a molecule on the surface of an infected cell, the NK cell is ‘switched on’ and stimulated to release cytotoxic granules.

Most healthy cells express Major Histocompatibility Complex I (MHCI) on their surface. The MHCI is recognized by inhibitory receptors on the surface of NK cells which ‘switch off’ the cell and prevent it from releasing its deadly granules. This mechanism protects healthy cells from destruction by natural killer cells. Pathogens (like bacteria) do not have MHCI on their surface, so they cannot inhibit the action of NK cells. Virus-infected host cells and cancer cells often lose their MHCI, making them unable to ‘switch off’ the NK cells and leaving them vulnerable to attack.

Natural Killer Cells vs. Cytotoxic T Cells

Natural killer cells are very similar to cytotoxic T cells. Both are types of lymphocytes, and both secrete granules containing perforins and granzymes to kill target cells. However, there are several key functional differences between the two.