Department director - V.G. Nesterenko, Doctor of Medical Science.
Laboratory of Immune System Regulation and Immunological Tolerance
Laboratory director - V.G. Nesterenko, Doctor of Medical Sciences.
The laboratory studies the impact that infectious and non-infectious factors have on the immunoregulatory functions of the body.
Research is being carried out using various models, using models involving streptococcal infections. The impact that group A streptococcus antigens (group polysaccharides, non-type-specific proteins) have on the occurrence of immunoregulatory disorders, and autoimmune reactions, is also being researched.
Panels of monoclonal antibodies have been obtained for chlamydia, streptococcus, rickettsia, and legionella antigens; these are used both for scientific research and to help diagnose infectious diseases.
Studies are also being done on stromal lymphoid tissue and hematopoietic organs, specifically the stromal progenitor cells that provide a tissue-specific microenvironment for the proliferation and differentiation of immunocompetent and hematopoietic cells. These studies concern age-related changes in the population of stromal progenitor cells (which are assumed to cause quite a number of diseases), as well as the involvement of stroma in the infectious disease process. Due to the fact that nowadays transplanting stromal cells is being used on a wider scale, the issue to what extent age-related shifts in stromal tissue are caused by the stromal cells themselves is taking on greater importance, as is to what extent they are due to external factors that emanate from the body. There is a range of problems under observation that are associated with determining the growth factors that are necessary for stromal cells to proliferate, and in particular the issue exists about whether the need for growth factors in stromal cells in different organs is the same, and whether stromal cells at different stages of differentiation can have different requirements concerning these factors.
In 2014, a group of employees from the Laboratory of Immunological Tolerance, headed by E.V. Nagurskaya, PhD in Biological Science, became a part of the laboratory, and owing to that the name of the laboratory was changed (it was previously the Laboratory of Immunity System Regulation).
Experts are developing models and studying the mechanisms governing the full and partial (split) tolerance that occurs naturally in adult bodies when infectious agents enter the mucous surfaces. The main objectives are to create a model for persistent urogenital infections, the characteristics for the systemic and local immune response to various infectious agents, and searching for ways to reverse immunological hyporeactivity to foreign antigens.
Laboratory of Natural Immunity
Laboratory director - T.N. Nikolayeva, Doctor of Medical Science
The main goal that the laboratory has is to study the mechanisms for natural resistance to infections, and to develop drugs with immunomodulatory activity.
The interaction of macrophages and lymphocytes with the waste products generated by microorganisms, and their pathogenicity factors that lead to inducing the production of cytokines (interleukins, tumor necrosis factor), phagocytosis, lymphocyte proliferation, and activating natural killer cells and delayed-type hypersensitivity effectors, is also something that is being studied.
Laboratory staff are involved in developing an array of drugs with antibacterial, antiviral, and immunomodulatory activity (Salmozan, Fosprenil (Phosprenyl), Maxidin).
Development and production work is being done on testing systems that take advantage of the coagglutination reaction and permit diagnosing salmonella and shigella infections.
Laboratory of Cellular Immunity
Laboratory director - A.V. Sanin, Doctor of Biological Science.
The main activities that the laboratory performs nowadays are the following:
Developing and studying the immunomodulatory properties of new drugs that possess immunomodulatory, antiviral, and adaptogenic properties. These medicinal products incorporate phosphorylated polyprenols from fir needles that have an inherently unique antiviral activity, organometallic compounds, and complex vitamin and amino acid mixtures that also contain biogenic activators and immunostimulants. Implementing the drugs into clinical practice as medicinal products to treat animals.
Developing and studying the immunomodulatory properties of a new type of drugs that have prolonged action that stems from creating them in microencapsulated forms. Studying the possibility of accomplishing targeted deposition using a magnetic field.
Studying how immunoglobulins interact with the receptor apparatus of immunocompetent cells (in particular, with the receptors for interleukin 2).
Studying the activity on the part of probiotics as one of the mechanisms for immunological training (maintaining the immune homeostasis system in a state of constant readiness), and one of the methods for rehabilitating the immune system in the body in conditions where homeostasis has been disrupted. Developing immune system probiotics, additionally including immunomodulators that enhance the effect of the intestinal immune system in cases where it has a disorder (congenital immunodeficiency, infection, parasitic invasion).
Laboratory of Immune System Mediators and Effectors
Laboratory director - A.P. Suslov, Doctor of Medical Science.
Created in 1987 on the premises of the Laboratory of Antibody Chemistry and Biosynthesis, which was previously overseen by A.E. Gurvich.
The main areas of focus for its research are:
Studying the defense mechanisms possessed by the immune system that are associated with the interaction of T-lymphocytes and phagocytes in normal conditions and during diseases
Developing immunochemical and cellular diagnostic methods for infectious diseases.
The subject matter of the research:
Observing subpopulations of T-lymphocytes and the soluble mediators produced by them that mobilize cellular immunity by activating phagocytes and regulating their chemokinetic mobility
Developing highly-sensitive, enzyme-linked, immunosorbent assays to help diagnose viral hepatitis B, as well as panels for testing the specificity and sensitivity of these kinds of testing systems
Producing sets of monoclonal antibodies for various HBsAg epitopes, and determining the characteristics of these antibodies
Developing screening and automated methods to assess the intensity of specific cellular immunity to viral hepatitis and chlamydia pathogens
Studying the role chlamydial infection plays in the development of cardiovascular diseases.
Laboratory of Stromal Cell Immune Regulation
Laboratory director - R.K. Chaylakhyan, Doctor of Medical Science
The area of focus for the research that in done in the Laboratory of Stromal Cell Immune Regulation took shape several decades ago thanks to A.Ya. Fridenstein, a corresponding member of the Russian Academy of Medical Sciences who was in charge of the laboratory, when a new category of cells was discovered for the first time in 1969, and namely stromal progenitor cells. When explanting suspended bone marrow and spleen cells in monolayer cultures, by day 12-14 discrete colonies that are visible to the naked eye form in them, which consist of several thousand fibroplasts. Using chromosome analysis on dividing cells in individual colonies, it was possible to show that each colony is a cell clone. This allowed determining the content of stromal precursor cells in blood-forming and immune system organs, and studying how their numbers change under various influences on the body (radiation, immunization, physical trauma). The content of these cells in the bone marrow ranges from 1-5x10'4 to 1x10'7. In the adult body, these are outside the proliferative pool. With a high level of adhesiveness, 90% of these cells attach themselves to the plastic within 30 minutes. The stromal fibroblasts that are part of the colonies, after being treated with trypsin, are easily removed from the plastic, and lend themselves to repeated passaging, forming diploid strains. Over the course of 2-3 months of cultivation, they double 37-39 times, which attests to the high proliferative potential inherent in these cells. Transplanting part of the cells from different passages into diffusion chambers leads to the formation of elements of bone, cartilage, and connective tissue in them. It has been demonstrated that osteogenic precursors multiply intensively as part of the strain.
The most important property of clonogenic stromal progenitor cells is their ability to form a specific microenvironment. For example, with the heterotopic transplantation of bone marrow and splenic fibroblast strains, blood-forming and lymphoid organs, respectively, are formed at the transplant site. Analyzing the proliferative and differentiation potencies for individual clone colonies also demonstrated their ability to form full-fledged blood-forming organs, and made it possible to prove that in an adult body bone and cartilaginous tissues have a common progenitor cell. The research that was conducted demonstrated that among the clonogenic stromal progenitor cells there is one category of cells that are, in terms of their potency, candidates to play the role of stem cells in the stromal tissue of the bone marrow.
Theoretical insights about the problems involved in stromal progenitor cells, and creating an experimental model for restoring bone tissue and hyaline cartilage defects made it possible to create and introduce a new biotechnological method at the clinic for restoring the integrity of bones and the hyaline cartilage in joints by transplanting autologous bone marrow fibroblasts grown outside the body into the area of the defect.
Laboratory of Cell-to-Cell Cooperation (includes a biophysical and radioisotope research group)
Laboratory director - S.B. Cheknev, Doctor of Medical Science.
The laboratory was established in 2002, and is geared toward studying the basics of human immunoreactivity, cell-to-cell cooperation in the immune system, and their endogenous and exogenous regulation. The laboratory was formed on the premises of the former Laboratory of Immunochemistry, which was overseen on a constant basis for many years by A.Ya. Kulberg, a corresponding member of the Russian Academy of Medical Sciences.
The laboratory does research aimed at developing technologies for modifying immunoactive proteins in blood serum; using these enables obtaining compounds with specified effector properties in relation to the immune system’s cells.
The cornerstone for these technological developments is studying extremely ancient mechanisms that govern the immunoregulation associated with biochemical processes in a closed cycle involving the transport and exchange of metal cations in the microenvironment of the cell. The workforce was able to prove the ability of proteins in the gamma globulin fraction of blood plasma to interact with copper and zinc cations, bind metal distributed in the periglobular space, retain it, and serve as cation carriers, at least in the local environment. Thanks to binding the metal, the gamma globulins themselves undergo pronounced conformational transformations, which causes a change in the intracellular signaling from the Fc receptors that are in turn activated by transformed Fc fragments of antibody molecules.
This research is being done in close cooperation with the laboratories for antiviral immunity, natural immunity, cytokines, and the microbiology of latent infections.
The biophysical and radioisotope research group carries out biophysical (ultracentrifugation, spectrophotometry, ultrasonic methods) and radioisotope studies using high-precision equipment in the bounds of executing a government-issued assignment from the Russian Federation Ministry of Health and Social Development for 2012-2013 to help support operations for the institute’s Central Isotope Department.