In order for the immune system to protect the human body from infections and diseases, there are different types of immune cells, each of which has been assigned different tasks. One of these immune cell types are the natural killer cells (NK cells).
natural killer cells are lymphocytes that belong to the cellular part of the innate immune system. Their task is to trigger the cell death of certain cells in a targeted manner.
There NK cells belong to the innate part of the immune system, they do not respond to specific antigens and can – unlike T cells and B cells – also do not form an immunological memory. Nevertheless, NK cells are often regarded as the interface between the innate and acquired immune system, since they influence the immune response through interaction with other defense cells.
For a better understanding of NK cells, you should have a good overview of the immune system and all its fellow players. The overview articles on the immune system and immune cells can help you!
Natural killer cells – formation and occurrence
Just like some components of the adaptive immune system (e.g. B-cells and T-cells), natural killer cells develop from lymphoid progenitor cells in the bone marrow. One also speaks of one lymphoid origin.
NK cells make up about 5–20% of lymphocytes. In certain organs, such as the uterus, they are found to be amplified. They are larger than B and T cells, but unlike them, they do not have antigen-specific receptors.
B and T cells work by binding to specific antigens. These antigens usually consist of structures belonging to a pathogen that is infecting the body. Cells with antigen-specific receptors must first bind an antigen in order to be able to carry out defense mechanisms. This ensures that only pathogens or infected cells are attacked and that the immune system does not accidentally attack healthy, endogenous cells. NK cells do not require this antigen specificity. They have other activation and control mechanisms for this.
Natural killer cells – task
Natural killer cells recognize damaged, foreign or virus-infected cells and bring about their controlled cell death (apoptosis). So NK cells destroy certain cells and thus work cytotoxic. They share this function with the cytotoxic T cells, sometimes also called T killer cells. You can now find out why NK cells are absolutely necessary and how you can tell them apart.
Since the function of killer T cells is important for understanding NK cells, feel free to read the article on T cells!
Immune response of killer T cells/cytotoxic T cells
In order for cytotoxic T-cells to be able to fulfill their function, they must first recognize antigen fragments that are bound to MHC-I molecules must be located. MHC-I molecules are found on all cells in the body that have a nucleus.
MHC stands for major histocompatibility complex and describes a molecule that plays a central role in the function of T cells Fulfills. You can think of them as little bowls on the surface of cells. Class 1 MHC molecules contain small pieces of proteins that are currently in the cell (peptide fragments). If a cell is currently infected or malfunctioning, pieces of the pathogen’s proteins or faulty peptide fragments end up in these bowls.
T cells have special receptors on their surface that allow them to bind to the MHC molecules on the surfaces of various cells and recognize the peptide fragments. If the peptide fragment comes from a pathogen that has just infected the cell, the T cell is activated and begins destroying the infected target cell. Cytotoxic T cells are consequently on MHC-I molecules on the surface of other cells in order to be able to fulfill their function.
However, this principle of the T-killer cells does not always work, because there is a problem: some viruses, for example, have the ability to suppress the MHC-I-dependent antigen presentation of their host cell. They result in fewer MHC-I molecules on the cell surface. With fewer MHC molecules, not as many virus fragments can then be presented to the outside. This is how these viruses manage to evade the T cells.
Not only viruses can reduce the number of MHC-I molecules on the infected cell. Tumor cells also have such a mechanism to evade the immune system and especially T-killer cells.
NK cell immune response
Natural killer cells have the ability to detect when there are fewer MHC molecules on the surface than normal (missing-self-Principle). It has so-called KIR receptors for this (Killer cell immunoglobulin-like receptors). Encounters one NK cell a healthy, normal cell, then KIR receptors bind to the MHC-I molecules and the NK cell does nothing. However, if the NK cell recognizes that there are fewer MHC molecules on the surface than normal, then it conducts the apoptosis the affected cell.
NK cells can cause cell death apoptosis induce by expelling perforins and granzymes. Perforins are proteins that have holes in the cell wall of the cell to be killed, through which then enzymes enter the cell from the granzymes. These enzymes cleave many cell-internal proteins, ultimately leading to apoptosis leads.
In addition to the KIR receptors have NK cells also many other receptors that can trigger apoptosis. The most important of these death receptors are z. B. NKG2D and NKp44. These are activating receptors: when an NK cell binds to such receptors, cell death is initiated.
This is where a collaboration with the MHC-binding receptors comes into play – finds the NK cells additional MHC-I molecules on the surface, the activating signal is simply ignored. However, if there are no or not enough MHC-I molecules on the surface of a cell, the activating signal cannot be suppressed and the NK cells apoptosis is initiated.
Signals that cause the opposite of activation, i.e. more of a block, are also referred to as inhibitory. In addition, proteins that bind to a receptor are known as ligands.
Also ask for the elimination of tumor cells NK cells an important immunological player. Without the recognition of antigens on the surface, T-killer cells cannot do anything against malignantly mutated cells. NK cells on the other hand, are not dependent on contact with antigens and can immediately initiate measures against tumor cells.
Cytotoxic T cells vs. natural killer cells
Below is a summary of the characteristics and differences between T killer cells and natural killer cells:
- T cell-mediated immune responses require MHC-I molecules, NK cells respond to the lack of MHC-I molecules.
- cytotoxic T cells have an antigen-specific receptor that receptors of NK cells are nonspecific.
- Both cell types cause the death of the target cell.
Natural killer cells – functions
Besides the recognition flacking MHC-I molecules, NK cells also have many other functions that are still being researched. These are all based on the fact that NK cells with their receptors to proteins or receptors bind to cell surfaces and then receive signals. These signals can NK cells then either restrain and leave inactive (inhibit) or activate and allow apoptosis to be initiated.
Detection of altered cells
NK cells have the function of recognizing altered proteins on cell surfaces (altered-self-Principle). NK cells also use special receptors for this. Proteins in a cell (including those on its surface) can change and build up incorrectly if the cell is stressed by a bacterial infection, for example. In this way, the NK cell can also recognize whether an infected cell is present and needs to be killed.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
Another function of natural killer cells is the Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). The basis for this process is the opsonization of pathogens or their components with antibodies.
antibody have two arms with binding sites that differ depending on the antibody. With these binding sites, they can attach to suitable structures that do not originate in the body. This includes structures from various pathogens, such as proteins of the cell wall from Bacteria. When antibodies bind to a pathogen, it can be more easily found and destroyed by other immune cells or components of the immune system (eg, macrophages, neutrophils, complement system). Therefore, in this case, antibodies also serve as a kind of marker for pathogens – also known as opsonization.
NK cells be able antibody tie that up pathogens fixed and then trigger the apoptosis of the pathogen cell. Here, too, apoptosis occurs through the release of perforin and granzymes. The ADCC is an example of how NK cells can be activated not only by cells, but also by humoral components of the immune system, which include antibodies.
This function of NK cells is now being further researched for a novel approach to cancer therapy. Initially, artificially produced antibodies are to be used that bind antigens that are often found on cells of certain tumors. Such antibodies are called, for example, rituximab or daratumumab. It’s thought that cancer cells get through this way NK cells and the ADCC mechanism can be killed better.
Cytokine-mediated activation of natural killer cells
Also cytokines – which are also a humoral component of the immune system – can activate NK cells.
cytokines are small proteins used by cells as signals for growth, movement and development. In the immune system, they play a special role in activating various types of immune cells and initiating inflammation.
Immune cells such as macrophages or dendritic cells release cytokines when they encounter infected cells. In addition to T-killer cells, this signal can also attract natural killer cells, which are then activated rapidly and vigorously to contain the infection and kill infected cells. This feature of NK cells is primarily important in viral infections.
People due to a genetic predisposition not enough NK cells produce are very susceptible to recurrent infections by the herpes virus.
The activation of immune cells by cytokines also works in the other direction. meets one NK cell On tumor cells, which were previously overlooked by other immune cells due to the lack of antigen presentation, it can release cytokines itself. Activate the cytokines