Natural killer (NK) cells: what they are and functions

In the 1970s, a type of lymphocyte was described with the ability to lyse tumors without needing to be previously sensitized or stimulated, as other lymphocytes such as cytotoxic T cells do require. To the way these cells, known as cells, react natural killer (NK), it was called natural cytotoxic reactivity.

These represent one of the three groups of lymphocytes of the immune system, apart from T and B cells. Unlike the latter, NK cells belong to the innate immune system and are part of the first line of defense against a wide range of pathogens..

Next, we will analyze in depth what they are and their different functions.

What are natural killer cells?

They are lymphocytes of the innate immune system that control various types of tumors and microbial infections by limiting their spread and subsequent tissue damage (Vivier et al., 2008). They are the main mediators of the body’s antiviral and antitumor responses.

As the name suggests, cells natural killer They are “naturally” cytotoxic and, unlike T cells, They do not require prior exposure to the antigen to trigger their antitumor effects ( Abel et al., 2018). Thus, they can destroy tumor cells spontaneously, that is, without having been previously sensitized.

These lymphocytes are abundant in certain mucous membranes and in the interstitium of the pulmonary capillaries, while their number is smaller in the lymph nodes. They have also been identified in the gastrointestinal tract, in the liver, in the spleen and in the peripheral blood where they correspond to 5-15% of circulating lymphocytes (Bueno and Cadavid, 2004).

Activation of natural killer cells

The activation of NK cells is regulated by a complex set of signals received from the receptors they express. In general, they can be activated by (Taborda et al., 2014):

Decreased expression of human leukocyte antigens (HLA) on the surface of the target cell, reducing inhibitory signals received through KIR receptors. Molecules expressed on abnormal cells that are recognized by the receptors of natural cytotoxicity. Cells with IgG antibodies bound to the plasma membrane, through a mechanism called antibody-mediated cellular cytotoxicity. Interaction with dendritic cells.

NK cells require at least two signals to activate. Not only does the decrease in HLA expression induce the activation of these cells, but signals from other receptors are also needed, which participate in the sum of signals that defines the activity of NK cells (Carrington and Alter, 2012). ).

Once activated, the cells natural killer release perforins and granzymes, inducing the rupture of the cell membrane of the enemy cell. Perforins are proteins that integrate into the membrane, causing the formation of pores and their consequent rupture. For their part, granzymes enter the cell and induce apoptosis (programmed cell death).

Functions of NK cells

The most notable functions of this group of lymphocytes are the following.

Cytotoxicity

It is a type of immune reaction in which a cell or microbe is coated by antibodies and destroyed by white blood cells. The cytotoxic function is the most recognized of NK cells and they exert it on tumor cells, cells transformed by viruses, cells infected with bacteria and other pathogens.

This function is carried out in three steps:

Recognition of target cellsContact with target cells and formation of immunological synapses.Death of the target cell induced by NK cells.

Cytokine secretion

Even though the main function associated with NK cells is cytotoxicity, in the case of their antimicrobial activity the cytokine secretory function is essential (Sepúlveda and Puente, 2000). Cytokines are proteins crucial for controlling the growth and activity of other cells of the immune system and blood cells.

Antitumor functions

NK cells can detect changes in the surface expression of human leukocyte antigens, which clearly qualifies them to detect cells that have undergone malignant transformation.

The antitumor activity of these cells is really important. One study showed that low cytotoxic activity of NK cells correlates with an increased risk of cancer (Imai et al., 2000).

Regulatory function

The cells natural killer can regulate adaptive immune responses, such as the generation of early and long-term antiviral T cell responses. In addition, they can increase or decrease immune responses and produce granulocyte and macrophage colony-stimulating factors (Schuster et al., 2016).

To conclude, NK cells are the first line of defense of our immune system against different antigens that can harm us. Its most important task is defense against infections, viruses and tumors. through its two main functions: cytotoxicity and cytokine secretion.

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