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Natural killer cell

life science Maturity 11-13 Next article →

Natural killer cells, often called NK cells, are specialized white blood cells. They belong to a group of cells known as large granular lymphocytes (LGL). They are also part of the innate lymphoid cell (ILC) family. These cells make up about 5% to 20% of all circulating lymphocytes in humans. NK cells are critical to the innate immune system. They provide a rapid response to threats like virus-infected cells and tumor cells. They also target stressed cells and other intracellular pathogens.

Missing self
Missing self

NK cells work through a complex balance of signals. They use activating receptors to find targets and inhibitory receptors to protect healthy cells. Most immune cells, like cytotoxic T cells, require a specific antigen to be presented on MHC class I molecules. However, some harmful cells hide by removing these MHC class I markers. NK cells are unique because they recognize these "missing self" signals. If a cell lacks these markers, the NK cell is triggered to attack. This ability to kill without prior sensitization is why they are called "natural killers."

HLA-Cw4
HLA-Cw4

Scientists classify NK cells into two main types based on their surface markers. The first type is known as CD56bright NK cells. These cells are mostly found in the bone marrow, liver, and skin. They primarily influence the immune system by releasing cytokines. They also tend to target highly proliferative cells, which may help regulate the immune response. The second type is the CD56dim NK cells. These are found mostly in the peripheral blood. They are highly effective at direct cell killing. They are also CD16 positive, which helps them perform antibody-dependent cellular cytotoxicity (ADCC).

PDB 1hkf EBI
PDB 1hkf EBI

When an NK cell identifies a target, it uses a precise biological mechanism to destroy it. The cell contains small granules filled with proteins like perforin and granzymes. When the NK cell reaches a target, it releases these granules. Perforin works by forming pores, or tiny holes, in the target cell membrane. This creates a channel that allows granzymes to enter the cell. Once inside, the granzymes induce apoptosis, which is a programmed form of cell death. This is safer than simple cell lysis because it destroys the threat without spreading viruses.

PDB 1hq8 EBI
PDB 1hq8 EBI

Research into these cells has a long and fascinating history. In 1966, Dr. Henry Smith at the University of Leeds observed that some cells could destroy tumors naturally. In the early 1970s, researchers Rolf Kiessling and Hugh Pross identified the specific cells responsible in mice. At the same time, Hugh Pross and Mikael Jondal discovered these cells in humans. These studies were supervised by professors Eva Klein and Hans Wigzell at the Karolinska Institute. In 1980, Timonen and Saksela achieved a major breakthrough. They were the first to visualize NK cells using a microscope.

PDB 1hkf EBI
PDB 1hkf EBI

NK cells use many different receptors to communicate with their environment. Natural cytotoxicity receptors (NCR) help mediate killing and the release of interferon gamma. Toll-like receptors (TLR) also play a role by recognizing patterns from pathogens. NK cells express various levels of these receptors, such as high levels of TLR-1. Inhibitory receptors, like the Killer-cell immunoglobulin-like receptors (KIR), protect healthy cells. KIRs recognize the MHC class I molecules on normal cells to prevent accidental attacks. This ensures the immune system only targets cells that are truly dangerous.

HLA-Cw4
HLA-Cw4

Understanding NK cells is vital for modern medicine. Scientists are currently researching how to use NK cell activity for new treatments. This includes potential therapies for cancer and HIV. Because NK cells can adjust to their environment, they may even form immunological memory. This allows them to respond more effectively to repeat infections. Their dual role in both innate and adaptive immunity makes them a major focus of biological study. They represent a bridge between immediate defense and long-term protection.

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