NK cells are part of the innate immune system and belong to the leukocyte group, the white blood cells. Their main function is to recognize infected and degenerate endogenous cells and to attack the cells directly by cytotoxic agents that partially dissolve the membrane of the target cell and initiate its programmed cell death. NK cells recognize “normal” somatic cells by MHC-I structures that healthy cells display on their surface.
What is the NK cell?
NK cells (natural killer cells) are a special type of white blood cell that patrol the blood and lymph. They are part of the innate immune system and recognize healthy, endogenous cells by special structures called major histocompatibility complex (MHC-I) molecules, which are only fully present in healthy cells. If cells with incomplete MHC-I molecules are identified, they are most likely infected by intracellular microorganisms or degenerated cells (tumor cells). The NK cell is then instantly activated and attacks the cell identified as infected or degenerated. They are capable of releasing cytotoxic substances that cause partial membrane dissolution in the target cells and can trigger apoptosis, or programmed cell death, in them. The counterpart to the NK cells are the T lymphocytes, which are part of the adaptive, the acquired immune system. They each specialize in a particular pathogen, which is revealed by additional structures on the cell surface and is called an antigen.
Anatomy and structure
NK cells form from lymphoid progenitor cells that originate in the bone marrow. The differentiated NK cells are released into the bloodstream and lymphatic system, where they immediately begin their patrols. As a distinctive feature, NK cells have numerous vesicles that contain cytotoxic substances such as perforin to dissolve the membrane of the attacked cell and proteases that serve to apoptotically disassemble the cell and viral RNA. The apoptosis of the target cell has the advantage that, for example, defined fragments up to individual amino acids are produced from proteins, which are reintroduced into the metabolism. NK cells are characterized by special receptors on their surface that react with the MHC-I structures of endogenous cells. These are KIR receptors (killer cell immunoglobulin-like receptors) and so-called natural cytotoxic receptors (NCR). KIR receptors are distinguished between activating and inhibitory receptors. NCRs are also important for friend-foe recognition and for the decision to attack or inactivate.
Function and Tasks
NK cells perform the main tasks of identifying and combating degenerate somatic cells. Degenerate somatic cells can be intracellular infected cells or tumor cells. To do this, NK cells rely on their receptor system, which can only check for the completeness of their MHC-I structures in target cells, but not additional structures such as antigens. Because some viruses use the specific weakness of NK cell recognition to deprive their “host cell” of the killer system, the NK cells work closely together with the cytotoxic T cells, which, as highly modern developments of evolution, are part of the adaptive, i.e. the acquired immune system. However, T cells are only specialized for a single antigen at a time, so a very large number of differently specialized T cells are required to cover the diverse spectrum of viruses that can be targeted for infection. NK cells could also be referred to as first-line defense cells because, upon recognition of a degenerate cell or a cell infected intracellularly by microorganisms, they can immediately undertake their fight. They can be likened to an armed police force that can not only reconnoiter but also intervene immediately with armed force if necessary. Because the NK cells are also tricked by certain intracellular pathogens – especially viruses – support from the cytotoxic T cells is useful. Time can play a major role in combating diseased cells, for example, to forestall exponential proliferation of viral RNA. The task of the NK cells is therefore to attack the target cell with cytotoxic substances in such a way that the viral RNA is also broken down to prevent it from replicating further.
Diseases
The immune system, in all its dynamics, is also subject to hormonal influences. Even sympathetic and parasympathetic system controls influence NK cells and cytotoxic T cells. Interestingly, when the body is sympathetically attuned to acute stress and thus to peak physical performance, NK cells are also increased and put on “heightened alert.” Cytotoxic T cells are slowed down by acute periods of stress, which was apparently set up by evolution because rapid immune responses are advantageous during an acute threat with risk of injury and corresponding risk of infection. In chronic stress conditions, the situation is different. Chronic stress leads to a weakening of the immune system, NK cells and T cells not only decrease in number but also in alertness. This is why high-performance athletes often show an increased susceptibility to infections shortly before major competitions. Reduced NK cell activity can also result from undesirable side effects due to drug exposure (chemotherapy) or radiation, while hereditary dysfunction in NK cells is extremely rare. The role of NK cells in tissue-specific autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis, and Hashimoto’s disease, or in systemic autoimmune diseases, has not yet been adequately elucidated. It is conceivable that NK cells have an activating effect in association with T cells, so that the T cells carry out the actual attacks on the body’s own cells. On the other hand, NK cells can also recognize activated, auto-reactive T cells as degenerate and kill them directly. This means that NK cells are very likely to have both initiating and promoting as well as curative effects in autoimmune diseases.