In experiments on the study of tumors are usually used the method of their transplantation - transplantation from one animal to another. The donor is an animal with a tumor caused by chemical carcinogens or viruses. These studies came to a solid scientific basis only after the inbred strains of mice were bred, within which animals do not differ genetically from each other. It is easy to understand that when a tumor is transplanted within a line (it is called syngeneic transplantation, or a transplanted syngenic tumor), donor tissue survives, and when transplanted from another donor (allotransplantation), the tissue dies. In the latter case, the difference between animals by the antigens of tissue compatibility, which determines the rejection of both normal and tumor cells, is obvious. This, by the way, explains why cancer is not a contagious disease; It was also proved that it was thanks to them that no one could ever get cancer with any contact with a sick person.
Transplantation of a syngenic tumor, it would seem, excludes antigenic differences. Therefore, it would be quite reasonable to assume that each transplanted clerk will produce offspring and all together they will quickly form a tumor. However, this “arithmetic” rule was not confirmed. Almost always, in order to cause the appearance of a tumor, it is necessary to transfer from one animal to another at least ... 105 - 107 tumor cells. If 10-50 thousand diseased cells are transplanted, they will die. But in cases of transplantation, not tumor cells, but normal syngeneic cells, they do not even die in a smaller number. The only satisfactory explanation for this difference is that even genetically “identical” tumor cells bear some hidden differences from non-tumor cells, and these differences are recognized by the immune cells of the recipient.Go
It has been established: after transplantation of syngeneic tumor cells to animals, most of them (from 70 to 99%) die in the first 4-24 hours, and the latent period of growth of any kind of tumor is much longer than the calculated one (based on the length of the division cycle of the introduced cells). From experiments on the transplantation of syngeneic tumors, several important conclusions can be drawn.
1. Recognition of tumor cells by a healthy organism is non-specific, that is, it occurs regardless of the type of tumor that occurs,
2. The response of the immune system to tumor cells has the character of a quick (immediate) reaction and does not require prior contact of the body with the antigens of this tumor. This report is implemented by the type of spontaneous cytotoxicity (spontaneously arising hostility of lymphocytes against tumor cells).
The latter position is very important because immunological reactions were divided into immediate reactions associated with the production of humoral antibodies (for example, with tetanus or diphtheria), and delayed-type reactions determined by cytotoxic lymphocytes that did not occur in the body in the first days after antigenic stimulation and later. These were taken and the reaction of antitumor immunity. It turned out, however, that immunity to tumors is associated not so much with late-appearing T-killers, as with cells of the first echelon of protection. These are the so-called macrophages and preexisting killing cells. For the first time, Soviet specialists I. Ya. Chernyakhovskaya, E. G. Slavina and G. Ya. Svet-Moldavsky in 1970 paid attention to the existence of such cells. Somewhat later, these cells were found in several foreign laboratories. They are called natural killers (EC), which reflects their natural origin and biological effect on tumor targets.Go
And no less important consequence arising from experimental observations. As mentioned above, the success of transplantation depends on antigens of tissue compatibility. Among them emit antigens I and II classes. Class I antigens are contained on the surface membrane of all the nuclear cells of the body and are recognized as foreign during allograft. Class II antigens are predominantly present on the cells of the immune system and determine the interaction of these cells during the immune response. From the above, it can be concluded that engraftment of syngeneic tumors in animals means their identity in terms of class I antigens.
Such an obvious conclusion was nonetheless not entirely fair. Often, under the influence of carcinogenic factors (chemical and physical products, viruses), the composition of class I antigens changes. If their number decreases, the tumor will be recognized immunologically, but this will not cause a rejection reaction. For the latter, it is necessary that the donor's tissue contains antigens that are absent in the recipient. Such tumors are called weakly immunogenic. The composition of class I antigens may increase due to the activation of normally inhibited (repressed) genes, then the tumors become highly immunogenic. The engraftment of such transplanted tumors in animals or the appearance of such spontaneous tumors in humans is possible only if the tumor escapes from immune surveillance. The mechanisms of this process will be discussed below.
Class I antigens in mice (the most genetically studied animals) are controlled by about 32 genes, in humans their number is incomparably greater. Therefore, their analysis and connection with tumor growth has not yet been largely studied. But already received a number of important facts. For example, oncologists, based on empirical observations, often did not recommend their patients to stay long in the open sun or to spend holidays in the south. In the experiment, indications were received that ultraviolet rays can change the composition of class I antigens and contribute to the appearance of rapidly progressing tumors. A feature of such tumors is their pronounced ability to “turn off” the protective cells of the body’s first defense - macrophages and EC. These data should be remembered by doctors when prescribing physiotherapeutic procedures in cases of suspected tumor growth.