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

What are NK cells? Let's take a look at their characteristics and how they protect the body.

You have probably heard of "killer cells". Also known as Natural Killer or, for short, NK cells, these cells are lymphoid cells.These cells are lymphocytes of the innate immune system and are responsible for neutralizing cells infected by viruses or bacteria, as well as Cancer cells.

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

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

NK cells: definition and general characteristics

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

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

What NK cells do is to destroy two types of cells: infected cells (viruses, bacteria...) and cancerous 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 shall see, NK cells act mainly thanks to a family of receptors called "Immunoglobulin-like receptors" (KIR), which allow them to respond to alterations in the immune system.which allow them to respond to alterations present in infected or cancerous cells whose HLA class I molecules (major histocompatibility complex) are altered. Later, we will discuss what this histocompatibility complex consists of.

KIR receptors

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

Function

How do NK cells work? What they do is destroy the aforementioned cells by attacking their plasma membrane, which causes a process called cytokines.This causes a process called cytolysis (or cytolysis), which consists of the rupture of the cell through the breakdown of its cell membrane; in this process, the cell also loses its genetic material and the vital processes it was carrying out are stopped.

But how do NK cells recognize infected or cancerous cells? Studies show that they probably do this through two mechanisms: either they detect these cells by recognizing a type of material they contain, called glycocalyx, which is altered, or through the loss, in these cancer cells, of the class I major histocompatibility complex (MHC).

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

Major histocompatibility complex

Recall that MHC is a family of genes located on one chromosome, namely chromosome 6.specifically chromosome 6 (in humans).

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

How are NK cells activated?

We have seen, broadly speaking, how NK cells function. But how are they activated by an infected or cancerous cell?

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

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

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

Functions

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

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

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

Recall that the latter 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 activation-induced cell death in T lymphocytes. Role of diacylglycerol kinase alpha. Doctoral dissertation. Institute of Biology and Molecular Genetics University of Valladolid-CSIC.
• Goldberg, Anna Carla; Rizzo, Luiz Vicente. (2015). MHC structure and function – antigen presentation. Part 1. Einstein (São Paulo) (en inglés) (San Pablo, Brasil: 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 (Revisión), 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.
• Sepúlveda, C. y Puente, J. (2000). Células natural killer y el sistema inmune innato en la patología infecciosa. Rev. méd. Chile, 128(12).