NK cells: what are they and what functions do they have in the human body?

Surely you have ever heard of "killer cells". Also known as Natural Killer or NK cells for shortThese types of cells are lymphocytes of the innate immune system, and are responsible for neutralizing cells infected by viruses or bacteria, as well as cancer cells.

Its proper functioning is essential to prevent many types of cancer, as well as other pathologies. In this article we will explain in detail what they consist of, how they work and how they are activated, and what their other functions are beyond destroying "malignant" or abnormal cells.

In addition, we will also explain its relationship with the KIR receptors and with the MHC (main histocompatibility complex).

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NK cells: definition and general characteristics

NK cells, also called Natural Killer (NK) cells, are lymphocytes of the innate immune system., whose main function is to protect our body. This type of cell represents one of the three groups of lymphocytes in our immune system, along with T and B lymphocytes.

But... What differentiates NK cells from T and B lymphocytes? The fact of belonging to the innate immune system, and of being part of the first line of defense against a very wide range of pathogens.

What NK cells do is destroy two types of cells: infected cells (by viruses, bacteria...) and cancer or tumor cells. On the other hand, they also regulate the different immune responses of the immune system; In addition, they are involved in the rejection of bone marrow transplants, in autoimmune processes and in the maintenance of pregnancies.

As we will see, NK cells They act mainly thanks to a family of receptors called "Immunoglobuline-like receptors" (KIR), which allow them to respond to alterations present in infected or cancer cells, whose HLA class I molecules (major histocompatibility complex) are altered. Later, we will discuss what this histocompatibility complex consists of.

KIR receivers

Thanks to the KIR receptors on NK cells, they can recognize infected and cancer cells in a very specific way; this is possible thanks to the signals they receive through many of the receptors of the cells malignant cells, which end up triggering their cytotoxicity, as well as the secretion of chemokines and cytokines.

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Functioning

How do NK cells work? what they do is destroy the aforementioned cells by attacking their plasma membrane, which causes a process called cytolysis (or cytolysis), and which consists of the rupture of the cell through the decomposition of its cell membrane; In this process, moreover, the cell loses its genetic material and the vital processes it was carrying out stop.

But how do NK cells recognize infected or cancer cells? The studies carried out show that they probably do so through two mechanisms: either they detect these cells by recognizing a type of material that contain, called a glycocalyx, and that is altered, or through the loss, in these cancer cells, of the major histocompatibility complex (MHC or MHC) class YO.

Specifically, NK cells have a series of receptors on their membrane that detect the presence of MHC class 1 in altered or abnormal cells; in healthy cells, these receptors are inhibited (that's why NK cells are able to distinguish between them, thanks to this highly efficient recognition system).

Major histocompatibility complex

Let's remember that MHC or MHC is a family of genes located on a chromosome, specifically chromosome 6 (in humans).

Its function is to encode leukocyte antigens (or histocompatibility antigens); These antigens, in turn, have the mission of presenting the antigens to the T lymphocytes, which allows different processes involved in the body's immune response to be activated.

How are NK cells activated?

We have seen, in broad strokes, how NK cells work. But how are they activated by an infected or cancerous cell?

they do thanks to a group of signaling proteins called interferons (IFNs); interferons are produced by host cells when a virus, bacterium, parasite or tumor cell infects them, through a feedback process.

Beyond interferons, NK cells they are also activated by other types of substances, such as interleukins-2, which are cytokines (a type of protein) synthesized in T lymphocytes. It should be mentioned here that NK cells activated by interleukins-2 in the laboratory are called "LAK cells".

On the other hand, NK cells have a series of specific receptors for immunoglobulin G (a type of antibody) on their surface; When these cells encounter a virus-infected cell, their antigens are presented on the infected cell (on its surface), and antibodies bound to the NK cell bind to the cell infected.

functions

NK cells are of great importance for health and for the proper functioning of our body, since they prevent infected cells from continuing to live and perpetuate themselves. This is thanks to its ability to recognize and kill these types of cells.

It could be said that NK cells constitute the body's innate first line of defense, which responds to infections and tumor transformations that occur in cancer cells.

In addition, these cells have a high discriminative power, since they can differentiate between cells infected by a virus and cells affected by a tumor.

Let us remember that these last cells are those that have undergone different malignant transformations in their structure. On the other hand, NK cells are also capable of differentiating between cells of the organism itself and "invading" or foreign cells.

Bibliographic references:

• Abbas, A., Lichtman, A. and Pillai, S. (2008). Cellular and Molecular Immunology. 6th Edition. Section IV: effector mechanisms of immune responses; Cytokines.
• Gil, R.A. (2005). Regulation of cell death induced by activation in T lymphocytes. Role of Diacylglycerol Kinase alpha. Doctoral Thesis. Institute of Biology and Molecular Genetics University of Valladolid-CSIC.
• Goldberg, Anna Carla; Rizzo, Luis Vicente. (2015). MHC structure and function – antigen presentation. Part 1. Einstein (São Paulo) (in English) (Sao Paulo, Brazil: Scielo), 13(1): 153-156.
• Mace ME, Dongre P, Hsu H-T, SinhaP, James AM, Mann SS, Forbes LR, Watkin LB, Orange JS (2014). Cell biological steps and checkpoints in accessing NK cell cytotoxicity. Immunology and Cell Biology (Review), 92: 245-255.
• Schleinitz N, March ME, Long EO. (2008). Recruitment of Activation Receptors at Inhibitory NK Cell Immune Synapses. PLOS ONE, 3(9): e3278.
• Sepulveda, C. and Bridge, J. (2000). Natural killer cells and the innate immune system in infectious pathology. Rev. med. Chile, 128(12).