Charakterystyka pracy socjalnej i edukacyjnej w szkółce niedzielnej wspólnoty religijnej

For the organization of social-pedagogical work with children in the religious community isused a variety of forms and methods that contribute to the implementation of this activity content. The author of the article conducted an analysis of the content of education used in Sunday schools and methods of didactic and educational work.W organizacji społeczno-pedagogicznej pracy z dziećmi we wspólnotach religijnych używa się różnorodnych form i metod, które wspierają realizację tego typu działań. Autorka artykułu przeprowadziła badania nad tym zagadnieniem i przedstwiła ich analizę

SARS-CoV-2 B cell receptor signatures in risk populations

Many individuals possess B cells capable of recognizing epitopes on the spike glycoprotein of SARS-CoV-2. In this issue of the JCI, Paschold and Simnica et al. interrogated the frequency of SARS-CoV-2–specific B cell receptor rearrangements in healthy subjects based on age and cancer status. The authors found that, while SARS-CoV-2–specific antibody signatures can be identified in the repertoires of young, healthy individuals, such sequences are less frequent in elderly subjects or cancer patients. Overall, this study sheds light on B cell repertoire restrictions that might lead to an unfavorable clinical course of COVID-19 infection in risk populations

In silico analysis of the structure of variable domains of mouse single-chain antibodies specific to the human recombinant interferon β1b

In silico analysis of the DNA encoding singlechain Fv antibodies (ScFv) specific to the human recombinant interferon β1b and α2b (rhIFNβ1b, rhIFNα2b) has been carried out. The V, D and J-gene segments, the complementaritydetermining (CDR) and framework (FR) regions, n-nucleotides as well as mutation rates which take place during the affinity maturation of the examined sequences have been determined. For the panel of ScFv against rhIFNβ1b isolated from an immune combinatorial cDNA library uniqueness of the CDRH3 loop by the length and amino acid composition has been shown. Multiple alignments with the nearest homologies from the NCBI databases have revealed that the sequences of ScFv obtained are new.Проведен in silico анализ структуры последовательностей ДНК, кодирующих специфические к интерферону β1b и α2b человека (rhIFN β1b, rhIFN α2b) одноцепочечные антитела (ScFv – single chain Fv): определены V, D и J сегменты, границы антиген связывающих (CDR) и каркасных (FR) участков, n нуклеотиды, а также величина мутационных процессов, которые имели место при аффинном дозревании последовательностей in vivo. Для представителей панели ScFv против rhIFN β1b, изолированных из иммунной комбинаторной библиотеки кДНК V генов, показана уникальность участка CDRH3 как по длине, так и по аминокислотному составу. Множественное выравнивание с ближайшими гомологами базы данных NCBI показало, что полученные нами последовательности ScFv являются новыми.Проведено in silico аналіз структури послідовностей ДНК, які кодують специфічні до рекомбінантного інтерферону β1b та α2b людини (rhIFN β1b, rhIFN-α2b) одноланцюгові антитіла (ScFv – single chain Fv): визначено V , D та J генні сегменти, межі антигензв’язувальних (CDR) та каркасних (FR) ділянок, n- нуклеотиди, а також величину мутаційних процесів, що мали місце при афінному дозріванні даних послідовностей in vivo. Для представників панелі ScFv проти rhIFN β1b, ізольованих з імунної комбінаторної бібліотеки кДНК V генів, показано унікальність ділянки CDRH3 як за довжиною, так і за амінокислотним складом. Множинне вирівнювання з найближчими гомологами бази даних NCBI показало, що одержані нами послідовності ScFv є новими

An ultralong CDRH2 in HCV neutralizing antibody demonstrates structural plasticity of antibodies against E2 glycoprotein

A vaccine protective against diverse HCV variants is needed to control the HCV epidemic. Structures of E2 complexes with front layer-specific broadly neutralizing antibodies (bNAbs) isolated from HCV-infected individuals, revealed a disulfide bond-containing CDRH3 that adopts straight (individuals who clear infection) or bent (individuals with chronic infection) conformation. To investigate whether a straight versus bent disulfide bond-containing CDRH3 is specific to particular HCV-infected individuals, we solved a crystal structure of the HCV E2 ectodomain in complex with AR3X, a bNAb with an unusually long CDRH2 that was isolated from the chronically-infected individual from whom the bent CDRH3 bNAbs were derived. The structure revealed that AR3X utilizes both its ultralong CDRH2 and a disulfide motif-containing straight CDRH3 to recognize the E2 front layer. These results demonstrate that both the straight and bent CDRH3 classes of HCV bNAb can be elicited in a single individual, revealing a structural plasticity of VH1-69-derived bNAbs

HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design

Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens

Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells

Semi-invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains self-tolerance remains unknown. iNKT cells constitutively express high levels of Nr4a1-encoded Nur77, a transcription factor that integrates signal strength downstream of the T cell receptor (TCR) within activated thymocytes and peripheral T cells. The function of Nur77 in iNKT cells is unknown. Here we report that sustained Nur77 overexpression (Nur77^(tg)) in mouse thymocytes abrogates iNKT cell development. Introgression of a rearranged Vα14-Jα18 TCR-α chain gene into the Nur77^(tg) (Nur77^(tg);Vα14^(tg)) mouse rescued iNKT cell development up to the early precursor stage, stage 0. iNKT cells in bone marrow chimeras that reconstituted thymic cellularity developed beyond stage 0 precursors and yielded IL-4–producing NKT2 cell subset but not IFN-γ–producing NKT1 cell subset. Nonetheless, the developing thymic iNKT cells that emerged in these chimeras expressed the exhaustion marker PD1 and responded poorly to a strong glycolipid agonist. Thus, Nur77 integrates signals emanating from the TCR to control thymic iNKT cell tolerance induction, terminal differentiation, and effector functions

Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance

A vaccine for hepatitis C virus (HCV) is urgently needed. Development of broadly neutralizing plasma antibodies during acute infection is associated with HCV clearance, but the viral epitopes of these plasma antibodies are unknown. Identifying these epitopes could define the specificity and function of neutralizing antibodies (NAbs) that should be induced by a vaccine. Here, we present the development and application of a high-throughput method that deconvolutes polyclonal anti-HCV NAbs in plasma, delineating the epitope specificities of anti-HCV NAbs in acute-infection plasma of 44 humans with subsequent clearance or persistence of HCV. Remarkably, we identified multiple broadly neutralizing antibody combinations that were associated with greater plasma neutralizing breadth and with HCV clearance. These studies have the potential to inform new strategies for vaccine development by identifying broadly neutralizing antibody combinations in plasma associated with the natural clearance of HCV, while also providing a high-throughput assay that could identify these responses after vaccination trials

Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity