Killers are born
What are natural killers?
What is the difference between T-killers and natural killers, which proteins trigger the mechanism of apoptosis and how the body protects itself from intracellular infections
Ravshan Ataullakhanov, Post-science
Natural killers are cells of innate immunity, capable of killing other cells of the body – tumor or infected with viruses. Natural killers are formed from progenitor cells that are born in the bone marrow. Their transformation into killers occurs in various tissues and organs (lymph nodes, spleen, liver, intestines, thymus, uterus, and others), where they turn into variants of natural killers with slightly different properties.
Natural killers are close relatives of T-killers. Both are living mobile container cells, inside of which there are bubbles with deadly contents and on the surface of which there are molecular sensors. With the help of sensors, the killer cell recognizes infected or tumor cells to be eliminated.
There are no ready-made T-killers. There are their predecessors – naive T-cells with a wide variety of recognizing sensors. Naive T cells are not ready to kill. These are a kind of live blanks. Initially, there are too few of them, so when and if their sensors meet an infected or tumor cell, the blanks will begin to multiply and at the same time acquire the properties of professional killer T cells. This process of reproduction and transformation takes days, or even weeks.
Natural killers are so called because they are ready to kill immediately, without preparation. The mechanism of action of a natural killer is the same as that of a T-killer: it carries the same granules in which poisons are hidden. The killer cell forms a hermetic contact with the victim cell and releases poison into this hermetic gap between the cells, which kills the wrong cell. The killer cell itself is protected from this poison.
Natural killers use several proteins as poisons: perforin, granzyme and granulisin. Perforin is embedded in the outer membrane of the victim cell and forms pores in the membrane through which granzyme and granulisin pass. They enter the cell, turn on its mechanism of apoptosis – self-destruction. Within 10-20 minutes, the cell will digest its contents to the simplest molecules and pack these safe remains into small pouches that phagocytes will willingly eat. So very carefully, without harming neighboring, healthy cells, an infected or tumor cell self-destructs at the command of a killer cell. A natural killer is a serial killer, he can hit 30-40 target cells in a row.
Sensors of T cells and natural killers recognize an infected or tumor cell in different ways. The T-killer recognizes miniature fragments of viral or mutant proteins presented on the cell surface in a kind of molecular showcases, MHC molecules (major histocompatibility complex, the main histocompatibility complex – VM). This is the law: each cell of the body represents on its surface elements of what is synthesized inside the cell. This is necessary so that the immune system can detect any painful changes in every cell of the body – signs of foreign, infectious molecules or its own molecules significantly changed as a result of mutations. Such molecular signs of the disease of our cell are recognized by the T-killer and kills the altered cell. Cruel, but effective. It is better to lose sick cells than to lead the body to death from infection or tumor.
Quite often, infected and tumor cells hide signs of the disease, without showing on the surface either showcase molecules, mutant proteins, or molecules of an infectious nature. This wonderful "stealth" strategy of a virus or tumor makes them invisible to T-cells, and, consequently, a formidable weapon in the form of T-killers becomes helpless against such cunning enemies. Here a natural killer comes to the rescue, whose sensors just make sure that showcase molecules are necessarily represented on the surface of each cell of the body. The absence or significant decrease in the number of MHC molecules (showcases) on the cell is considered by the natural killer as a sign sufficient for a death sentence. Such a "bare" cell without a passport for survival must die – it receives an order for apoptosis from a natural killer and very carefully self-destructs.
Natural killers are important for protection against intracellular infections, such as viruses, and for protection against tumors. If this defense mechanism is violated, people suffer from recurrent viral infections, they are more likely to develop tumors. Life without natural killers is full of diseases and risks.
About the author:
Ravshan Ataullakhanov – Doctor of Medical Sciences, Professor, Head of the Department of Immune Biotechnology, Head of the Laboratory of Immune Activation of the Institute of Immunology of the FMBA of Russia, Professor of the Department of Immunology of the Faculty of Biology of Lomonosov Moscow State University.
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17.07.2017