Natural killer cells are lymphocytes that belong to the same family as B and T cells. They are cytotoxic cells of the innate immune system and circulate in the body looking for 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.

Natural killer cells are cytotoxic cells of the innate immune system
Natural killer cells destroy infected host cells and cancer cells

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 and T cells and play an important role in limiting the spread of infection. When an 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 granzyme that work together to stimulate apoptosis in the infected cell.

Where are natural killer cells found?

Natural killer cells are immune guardians that roam the body looking for infected and cancerous cells. Because of this, NK cells are found throughout the body and found in most human tissues. They are found in their highest concentrations in the bloodstream, in the uterus, in the lungs and in the liver.

Origin of the natural killer cells

Natural killer cells develop from stem cells in the bone marrow, lymph nodes, spleen or tonsils. Mature NK cells make up about 5 to 20% of the circulating white blood cells in the human body.

Natural killer cells develop in the bone marrow, spleen, lymph nodes and tonsils
All lymphocytes develop from blood stem cells

Function of natural killer cells

Natural killer cells are named because they are “naturally” cytotoxic, which means that (unlike cytotoxic T cells) they do not need antigen exposure to be activated. Their key role is to limit the spread of infections in the body by destroying infected host cells and locating and killing cancer cells.

NK cells vs. viral infection

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

Natural killer cells limit the spread of viral infections
NK cells attack virus-infected host cells

This mechanism of induction of cell death keeps viral agents in the host cell and therefore limits their spread to other parts of the body. If NK cells only use 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 creates antigen-specific cytotoxic T cells. Once activated, the cytotoxic T cells can clear the infection from the body.

NK cells versus cancer cells

NK cells also attack and destroy cancer cells in the body. They treat cancer cells the same way they treat virus infected cells. by releasing cytotoxic granules containing perforin and granzym. 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 the aforementioned apoptotic enzymes Caspases, which leads to cell death.

Natural killer cells target and destroy cancer cells
Natural killer cells secrete granules to kill cancer cells

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 trigger the release of cytotoxic granules in the NK cells, but do not kill healthy “self” cells. NK cells “know” which cells are healthy and which are infected thanks to molecules 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 “turned on” and stimulated to release cytotoxic granules.

Natural killer cells identify target cells based on their
NK cells identify target cells based on molecules on their surfaces

Most healthy cells express Main histocompatibility complex I. (MHCI) on their surface. The MHCI is recognized by inhibitory receptors on the surface of NK cells that “turn off” the cell and prevent it from releasing its deadly granules. This mechanism protects healthy cells from being destroyed by natural killer cells. Pathogens (such as bacteria) do not have an MHCI on their surface, so they cannot inhibit the action of NK cells. Virus infected host cells and cancer cells often lose their MHCI, leaving them unable to turn off the NK cells and making 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 that contain perforins and granzymes to kill target cells. However, there are several major functional differences between the two.

Natural killer cells

Cytotoxic T cells

Innate immune system Adaptive immune system
Do not target specific antigens Target a specific antigen
No antigen presentation is required to be activated Must be activated by antigen presentation

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