The main biological characteristics of viruses of the Coronaviridae family are presented. The features of the immunopathogenesis of these infections are analyzed. It was found that the structural proteins of the spine, membrane, envelope and nucleocapsid play an important role in the immunopathogenesis of COVID-19 infection. They are associated with hyperactivation of neutrophils and monocytes-macrophages, secreting large amounts of pro-inflammatory cytokines and chemokines. This contributes to the development of a cytokine storm and an unfavorable prognosis of the disease. A particularly high risk of developing pneumonia exists against the background of an increase in the production of: macrophage inflammatory protein-1 alpha, macrophage chemotactic protein, interleukin 8. At the height of infection in some patients, macrophages and dendritic cells infected with SARS-CoV-2 lose their ability to produce type I interferons and pro-inflammatory cytokines. On the part of cellular immunity, a significant decrease in the number of CD4+ and CD8+-lymphocytes was noted. Among IgG sub-isotypes, IgG3 antibodies had the highest reactivity, and IgG1 antibodies were less reactive. Antibodies to spike protein with low specificity or low titer do not neutralize the virus and contribute to the contamination of immunocompetent cells via Fc receptors. Low-affinity antibodies or their low levels can contribute to increased cell sensitivity to SARS-CoV-2 and the development of severe forms of COVID-19 disease.
This study described the perspective and significance of using complex vaccine systems in improving immunoprophylaxis of major infectious diseases of various etiologies and genesis. Immunobiological drugs traditionally used for this purpose, along with the advantages, have disadvantages, such as increased reactogenicity and development of post-vaccine reactions and complications in some cases. Such adverse effects are serious obstacles to immunoprophylaxis on a mass scale. This circumstance was the reason for the improvement of immunoprophylaxis, and the main focus was the creation of chemical, recombinant, and subunit vaccines. However, compared with traditional drugs, these vaccines have inferior effectiveness, even if they are practically reactogenic and do not lead to the development of post-vaccine reactions and complications. The main approaches to the development of effective and safe methods of immunoprophylaxis are considered based on the development of complex vaccine systems, and the components can be protective antigens, biologically active substances of the corresponding microorganisms, adjuvants applied or embedded in the corresponding biologically active, and safe biotechnological platforms. Among the latter, nanoparticles and microparticles of polylactoglycolic acid, liposomes, lipids, and copolymers are recognized as the most suitable for the construction of complex vaccine systems. This paper highlighted new trends in the development of these methods of immunoprophylaxis and their advantages in comparison with traditionally used immunobiological drugs. Moreover, prospects are characterized and examples of developed vaccine preparations are presented. The mechanisms of action of postvaccination immunity and factors that influence its formation are described.
The phases of embryo development, starting with the formation of gametes and germlines, are considered. This study described the differences in the selection of germ and somatic cells. The formation of true germ cells is associated with the induction of bone morphogenetic protein. The zinc-finger transcription factor is the marker of the formation of true germ cells in primates. True germ cells have two types: germ cells that form endoderm and those that form an epiblast. Their differentiation is provided by the growth factor of fibroblasts due to the signaling protein FGF4, which interacts with the FGFR2 receptor in the primary endoderm. The migration of germ cells is controlled by the factors of stromal cells. The implantation of a fertilized egg is associated with the peculiarities of the differentiation of the trophectoderm and the influence of transcription factors. Since stem cell lines are isolated from non-brain tissues, their origin and development remain not fully established. In mice, the chorion is formed from a small area of trophectoderm covered with an out-of-the-mouth mesoderm on the proximal end of the egg lumen. In humans, the chorion, together with its basisnon-embryonic mesodermis the earliest appearance of tissue emanating from the primary endoderm. Modern research has confirmed the possibility of obtaining clones from the nuclei of early blastomere embryos. However, the use of cell nuclei at later stages yielded unsatisfactory results. The use of embryonic stem nuclei has produced much better results than the use of cells in the later stages of development. Therefore, whatever the source of the cores, they should be in the G0 or G1 phase, but not in G2.
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