Immunological aspects of COVID-19: What do we know?

The newly emerged coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) and the disease that it causes coronavirus disease 2019 (COVID-19) have changed the world we know. Yet, the origin and evolution of SARS-CoV-2 remain mostly vague. Many virulence factors and immune mechanisms contribute to the deteriorating effects on the organism during SARS-CoV-2 infection. Both humoral and cellular immune responses are involved in the pathophysiology of the disease, where the principal and effective immune response towards viral infection is the cell-mediated immunity. The clinical picture of COVID-19, which includes immune memory and reinfection, remains unclear and unpredictable. However, many hopes are put in developing an effective vaccine against the virus, and different therapeutic options have been implemented to find effective, even though not specific, treatment to the disease. We can assume that the interaction between the SARS-CoV-2 virus and the individual's immune system determines the onset and development of the disease significantly.     

Genetic bases of diversity of the repertoire of immunoglobulins in application to diagnostics of clonality of B-cell lymphoid populations

Molecular mechanisms underlying the formation of B-cell lymphomas in connection with processes associated with the maturation of B lymphocytes are reviewed. The currently used diagnostic methods do not always distinguish lymphomas from reactive changes of the lymphoid tissue. The principle of the molecular genetic method ofclonality detection in lymphocyte populations, technical problems, and the strategy of its application in clinical diagnostics of lymphomas are described in detail.     

The multiple shark Ig H chain genes rearrange and hypermutate autonomously

Sharks and skates are representatives of the earliest vertebrates with an immune system based on V(D)J rearrangement. They possess a unique Ig gene organization consisting of 15 to >50 individual IgM loci, each with one VH, two DH, one JH, and one set of constant region exons. The present study attempts to understand how multiple Ig genes are regulated with respect to rearrangement initiation and to targeting during somatic hypermutation. The linkage of three single-copy IgH genes was determined, and single-cell genomic PCR studies in a neonatal animal were used to examine any relationship between relative gene position and likelihood of rearrangement. Our results show that one to three IgH genes are activated independently of linkage or allelic position and the data best fit with a probability model based on the hypothesis that V(D)J rearrangement occurs as a sequence of trials within the B cell. In the neonatal cell set, two closely related IgH, G2A, and G2B, rearranged at similar frequencies, and their membrane forms were expressed at similar levels, like in other young animals. However, older animals displayed a bias in favor of the G2A isotype, which suggests that although rearrangement at G2A and G2B was randomly initiated during primary repertoire generation, the two very similar IgM sequences appear to be differentially expressed with age and exposure to Ag. We performed genomic single-cell PCR on B cells from an immunized individual to study activation-induced cytidine deaminase targeting and found that hypermutation, like V(D)J rearrangement, occurred independently among the many shark IgH.     

Bacteria and algae in stream periphyton along a nutrient gradient

1. Stream riffles in southern Ontario and western Quèbec were sampled for biomass (58 stations from 51 streams) and production (22 stations from 21 streams) of algae and bacteria in periphyton to test the hypothesis that bacteria in benthic biofilms compete with algae for nutrients. 2. Algal and bacterial biomass were positively correlated, as were algal and bacterial production. Bacterial production was also positively correlated to algal and bacterial biomass, but the relationship was not significant. The ratio of algal to bacterial biomass did not vary with nutrients whereas algal production tended to increase with nutrients more rapidly than bacterial production. 3. Instream nitrogen concentrations explained 38–58% of the variability in algal biomass and production. Bacterial abundance explained an additional 9–29% of the residual variance in algal production and biomass. However, the relationship between bacterial abundance and algal production and biomass, once nutrients were taken into account, was positive, in contrast to the predicted effect of competition. 4. Hence, we reject our original hypothesis that bacteria in biofilms compete with algae for nutrients and instead suggest that bacteria and algae in biofilms coexist in an association that offers space and resources to sustain production of both groups of organisms.     

Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. We demonstrate that Abs generated against conserved bacterial polysaccharides are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. A reduction in Ag uptake, cell influx, cell activation, and cytokine production occurred in the presence of anti-polysaccharide Abs, resulting in a striking decrease in the severity of allergic airway disease in mice. Overall, our results suggest that Ag exposure-derived from environmental sources, self-antigens, or vaccination-during the neonatal period has dramatic effects on the adult Ab response and modifies the development of allergic airway disease.     

Genetic bases of the repertoire of immunoglobulins in application to diagnostics of clonality of B-cell lymphoid populations

Molecular mechanisms underlying the formation of B-cell lymphomas in connection with processes associated with the maturation of B-lymphocytes are reviewed. The currently used diagnostic methods do not always distinguish lymphomas from reactive changes of the lymphoid tissue. The principle of the molecular genetic method of clonality detection in lymphocyte populations, technical problems, and the strategy of its application in clinical diagnostics of lymphomas are described in detail.     

Electron-cytochemical and morphometric study of the activity of several enzymes in thyrocyte metochondria during malignant degeneration]

Cytochrome oxidase and succinic dehydrogenase activities were studied in the mitochondria of rat thyroid cell during experimental malignization by means of the electron-cytochemical and morphometric methods. The activity of these enzymes in the mitochondria changed depending on the stage of malignization: at the early stages it approached the normal activity, and at the later stages (precancer)--it decreased and approached the mitochondrial activity of cancer cells. A sharp decrease in the activity of the enzymes under study in the morphologically changed mitochondria of cancer cells may characterize their qualitative changes.     

New horizons of adenosinetriphosphate energetics arising from interaction with magnesium cofactor

MD DFT:B3LYP (6-31G** basis set, T = 310 K) method is used to study interactions [singlet (S) and triplet (T) reaction paths] between adenosinetriphosphate, ATP⁴⁻, and [Mg(H₂O)₆]²⁺ in water environment, modeled with 78 water molecules. Computations reveal the appearance of low and high-energy states (stable, quasi-stable, and unstable), assigned to different spin symmetries. At the initial stage of interaction, ATP donates a part of its negative charge to the Mg complex making the Mg slightly charged. As a result, the original octahedral Mg complex loses two (S state) or four (T state) water molecules. Moving along S or T potential energy surfaces (PESs), Mg(H₂O)₄ or Mg(H₂O)₂ display different ways of complexation with ATP. S path favors the formation of a stable chelate with the O1–O2 fragment of ATP triphosphate tail, whereas T path favors producing a single-bonded complex with the O2. The latter, being unstable, undergoes a further conversion into a spin-separated complex, also unstable, and two metastable S complexes, which finally arise in two stable, low-energy and high-energy, chelates. The spin-separated complex experiences rapid decomposition resulting in the production of a highly reactive adenosinemonophosphate ion-radical •AMP, early observed in the CIDNP experiment (Tulub 2006). Biological consequences of the findings are discussed.     

Preservation of photosynthetic electron transport from senescence-induced inactivation in primary leaves after decapitation and defoliation of bean plants

The comparative effects of decapitation and defoliation on the senescence-induced inactivation of photosynthetic activity in primary leaves of bean plants were investigated. Decapitation was performed during different phases of bean plant ontogenesis, immediately after the appearance of the 1st, 2nd, 3rd and 4th composite leaf. In addition, we examined a variant with primary leaves and stem with an apical bud, but without composite leaves, i.e. defoliated plants. Analyses of chlorophyll fluorescence, millisecond delayed fluorescence and absorption at 830nm in primary leaves were undertaken to investigate the alterations in photosystems II and I electron transport during the decapitation-induced delayed senescence in the non-detached leaves. Analysis of the OKJIP transients using the JIP-test (see [Strasser R, Srivastava A, Tsimilli-Michael M. Analysis of the chlorophyll a fluorescence transient. In: Papageorgiou G, Govindjee, editors. Chlorophyll a fluorescence: a signature of photosynthesis. The Netherlands: Kluwer Academic Publishers, 2004; pp. 321-362]) showed an increase in several biophysical parameters of photosystem II in decapitated plants, specifically, the density of active reaction centers on a chlorophyll basis, the yields of trapping and electron transport, and the performance index. We also observed a decrease in the absorbed light energy per reaction center. Such a decrease in light absorption could be a result of the photosystem II down regulation that appeared as an increase in Q(B)-non-reducing photosystem II centers. The effect was identical when all leaves except the primary leaves were removed. The variant with a preserved apical bud, the defoliated plant, showed values similar to those of decapitated plants with primary leaves only. The changes in the induction curves of the delayed fluorescence also indicated an acceleration of electron transport beyond photosystem II in the decapitated and in defoliated plants. In these plants, the photosystem I-driven electron transport was accelerated, and the size of the plastoquinone pool was enhanced. It was established that decapitation can retard the senescence of primary leaves, can expand leaf life span and can cause activation of both photosystems I and II electron transport. The decapitation procedure shows similarities to the process of defoliation. The overcompensation effect that is developed after defoliation could initially be manifested as an acceleration of the linear photosynthetic electron flow in the rest of the leaves.