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First line of defense

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Bred hairless mice, hereditarily deprived of the thymus, puzzled researchers; How do these mice resist the development of tumors? It turned out that the absence of T-lymphocytes in these animals is compensated by the increased number and activity of other cells - natural killer cells (EC). These cells appear in mice 2-3 weeks after birth, and after a similar period they reach the peak of their activity. In nudes up to 6 weeks of age, human tumors take root and metastasize, but in an adult state, this effect can be achieved only after irradiating the mice or after introducing antibodies to EC cells.

Relatively recently, experimenters developed a new, so-called "beige" breed of mice that have a genetic defect EC. In these mice, hypersensitivity to the development of tumors induced by viruses and chemical carcinogens is noted. Thus, on sharply differing experimental models, a convincing pattern can be traced: the high activity of the EC is associated with resistance to tumor growth, and low activity with low resistance to cancer.

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EC cells are an autonomous system of lymphocytes, independent of the effects of the thymus. Today it is established that the EC is not homogeneous cells, but a group of various performers of cytotoxic function. The main thing that distinguishes them from other cytotoxic cells (T-killers, cytotoxic macrophages, neutrophils) is the ability to kill tumor targets without prior sensitization. ECs are resistant to gamma rays, they are not even disarmed by the radiation dose of 1000P, which is detrimental to other cytotoxic cells.

It is assumed that the earliest cells, the predecessors of the EC, can go in one of two ways of development: either they enter the thymus and then develop as T-lymphocytes, or bypass the thymus and differentiate into T-independent EC cells. At the same time, one cannot exclude the possibility of interconversion of T-cells into EK-cells, and vice versa. The introduction of thymus hormones nudam reduces their EC activity, and the removal of the thymus in normal mice increases the number of natural killer cells. In humans, ECs are represented predominantly by large granular lymphocytes with a round or reniform nucleus, pronounced chromatin and a protruding nucleolus.

Normally, the main function of the EC is to destroy normal cells infected with viruses and tumor cells. The latter is not an end in itself, since the immune system eliminates all cells with the wrong development program. Therefore, along with the tumor, some immature hematopoietic elements are also removed. In general, the task of a system of cells with spontaneous cytotoxicity is to monitor the appearance of cells with an altered order of molecules on the cell membrane. For their part, the function of EC cells is regulated by other cells of the immune system.

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Since ECs appear only after birth, their exogenous effects are stimulated. A special place among them belongs to viruses. During the interaction of viruses with cells, interferon is formed, which serves as a key regulator of EC activity. It not only promotes the maturation of EK, but also expands the range of their actions to different targets. EC cells are also activated by interleukin-2, which proves the influence of T-helpers on them (see below). Finally, EC activation is achieved by the mutual cultivation of lymphocytes from different donors. All this only underlines the general pattern: the function of the responsible cells in the body is stimulated by different, complementary physiological mechanisms.

The more immunogenic the tumor, the more sensitive their cells are to cytotoxic damage. This action of the EC on target cells includes four main stages: recognition of target antigens by killers, active reproduction of EC, contact with the surface of the target and lysis itself, or, as otherwise called, “fatal impact”. The first two stages are associated with magnesium ions, the second two with the presence of sodium ions.

The cytotoxic effect of EC on target cells can be limited only by damage to the membrane. Such a transient violation of the outer membrane of targets is called membrane toxicity; it can serve as an intermediate stage of lethal shock. Membranotoxicity and cytotoxicity with irreversible changes in the cytoplasm are the instruments by which the elements of the body’s urgent response provide a fine degree of conformity and adaptation of all the cooperating cells of the body.

In spontaneous tumors, particularly in cancer patients, the EC activity is usually markedly reduced. The cause of inhibition of EC is the tumor cells themselves, in particular, this is achieved by their production of a factor that suppresses EC. In such cases, the cause should not be confused with the effect; the weakening of the EC in various types of tumors, especially evident in cases of leukemia, does not contradict the concept of immune surveillance, but reflects damage to the body's resistance under conditions of tumor growth.