Features of the functioning of immunological tolerance during pregnancy (literature review)
Authors:   Dnipro State Medical University, Ukraine, Panov V.V. , Duka Yu.M. ,   Dnipro State Medical University, Ukraine
Published: July 2023

Pregnancy is a special state in a woman’s life, which can definitely be considered an «immunological paradox», because the growth of a genetically «alien» fetus takes place in a woman’s body. Despite the direct contact between cells of fetal origin (syncytiotrophoblast) and cells of the maternal immune system, which are in excess in the decidual membrane of the uterus, rejection of the semi-allogeneic fetus does not occur. A state of permanent natural immunological tolerance, during which the body does not respond to certain antigens expressed by trophoblast cells, while maintaining the ability to respond immunologically to other immunogens is the opposite phenomenon of the immune response, it is acquired by the body during its development and is not genetically determined. Purpose - to analyze the phasing of immunological changes in the mother’s body, which are aimed at the development and preservation of pregnancy, to specify their role in the correct flow of placental waves, prevention of the development of placental dysfunction and obstetric complications associated with it. A review of modern medical literature on the processes of immunological changes during trophoblast invasion and placentation in early pregnancy is given. For a more detailed understanding, the influence of each link of the immune response in the process of developing immune tolerance was analyzed. It has been established that for the development of a normal pregnancy there is a genetically programmed immune mechanism that ensures a decrease in the local and systemic immune response to the semi-alien implanted blastocyst, embryo and fetus. This is achieved through the step-by-step course of three phases of immunological shifts: the unfolded immune conflict; suppression of the immune response and intense immune conflict. The physiological course of gestation and the development of the placenta, in which the balance between the processes of neoangiogenesis and apoptosis is maintained, is ensured by adequate expression of HLA-G locus molecules by trophoblast cells, inhibition of Th1-type cytotoxic reactions against placenta cells by the mother's body. Analyzed changes in the cytokine balance, which shifts towards immunosuppressive cytokines, which suppress cellular immune reactions and stimulate the production of blocking antibodies, the quantitative composition of which can be considered decisive when carrying a genetically foreign fetus. Consequently, a relative secondary cellular immunodeficiency is formed, which is mainly due to a deficiency of circulating T-helper/inducers, a decrease in the CD4/CD8 immunoregulatory index and suppression of the functional activity of the T-cell immune system. It has been proven that impaired immunological tolerance, trophoblast invasion and vascular remodelling processes controlled by the maternal immune system at the local and systemic levels lead to early reproductive losses, premature birth, placental dysfunction, and are associated with fetal growth retardation syndrome, pre-eclampsia and other complications. No conflict of interests was declared by the authors.