138 research outputs found

    T cell Allorecognition Pathways in Solid Organ Transplantation.

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    Transplantation is unusual in that T cells can recognize alloantigen by at least two distinct pathways: as intact MHC alloantigen on the surface of donor cells via the direct pathway; and as self-restricted processed alloantigen via the indirect pathway. Direct pathway responses are viewed as strong but short-lived and hence responsible for acute rejection, whereas indirect pathway responses are typically thought to be much longer lasting and mediate the progression of chronic rejection. However, this is based on surprisingly scant experimental evidence, and the recent demonstration that MHC alloantigen can be re-presented intact on recipient dendritic cells-the semi-direct pathway-suggests that the conventional view may be an oversimplification. We review recent advances in our understanding of how the different T cell allorecognition pathways are triggered, consider how this generates effector alloantibody and cytotoxic CD8 T cell alloresponses and assess how these responses contribute to early and late allograft rejection. We further discuss how this knowledge may inform development of cellular and pharmacological therapies that aim to improve transplant outcomes, with focus on the use of induced regulatory T cells with indirect allospecificity and on the development of immunometabolic strategies. KEY POINTS Acute allograft rejection is likely mediated by indirect and direct pathway CD4 T cell alloresponses.Chronic allograft rejection is largely mediated by indirect pathway CD4 T cell responses. Direct pathway recognition of cross-dressed endothelial derived MHC class II alloantigen may also contribute to chronic rejection, but the extent of this contribution is unknown.Late indirect pathway CD4 T cell responses will be composed of heterogeneous populations of allopeptide specific T helper cell subsets that recognize different alloantigens and are at various stages of effector and memory differentiation.Knowledge of the precise indirect pathway CD4 T cell responses active at late time points in a particular individual will likely inform the development of alloantigen-specific cellular therapies and will guide immunometabolic modulation

    Possibilities of ADS-B Implementation into FOC Systems

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    Media components influence viral gene expression assays in human fetal astrocyte cultures

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    In vitro neurovirological studies of viral infectivity or viral gene expression may be confounded by the mulHple neural cell types and/or fibrob last contamination present in early passage cultures prepared from dissociated human central nervous system (eNS) tissue. We have developed highly enriched astrocyte cultures for neurovirological study by culturing in a serum-free defined medium, 816, supplemented with basic fibroblast growth factor (FGF-2). Subculture in this medium selects against fibroblast proliferation and favors sustained proliferation of a highly enriched glial fibrillary acidic protein (GFAP)-positive cell population. These astrocytes support productive replication of cytomegalovirus (CMV) and transient expression of transfected CMVand human immunodeficiency virus type 1 (HIV-l) viral promoters. By comparison, CNS cultures developed in standard serum-contain ing medium initially contain predominantly astrocytes, but show increasing contamination with fibroblasts with sequential passage. These cultures support CMV viral synthesis in both fibroblasts and astrocytes, cell types distinguishable only by immunostaining for cell specific antigen. CMV or HIV-l promoter activities, quantitated by transient gene expression assays, are distinctly lower in eNS cultures maintained in serum-containing medium

    Place and Role of Master's Degree Programs ‘Pedagogic Education’, ‘Psychological and Pedagogic Education’ and ‘Psychology’ in the System of Continuous Professional Development of Teaching Staff

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    A new look at the system of training in-service teachers and innovative strategies for the organization of teacher education has led to the need to rethink master's degree programs as one of the most important ways of professional growth of the teacher. The purpose of the article was to determine the place, purpose, and role of master’s degree programs. The main research method used for the purposes of this research was an experimental study of the organization of master’s degree programs as a point of professional growth of teachers. The analysis was based on the programs’ features with regard to the stages of higher education, on the one hand, and, on the other, in relation to the courses of professional development and the centers of continuous professional development of teachers in Russia. The authors proposed and tested the model of organization of teacher training relied on contingent features, specifics of the programs, and organization of educational process. The activity of students was also analyzed with an aim of involving them in scientific understanding of pedagogical realities. A comparative analysis of the results of traditional advanced training courses and the model of master’s programs that the authors proposed has shown that students’ satisfaction with the learning process, positive perception of the educational process, and a clear vision of their professional growth are stronger at the master’s programs, while continuing professional development courses show more risks and do not always meet teachers’ expectations
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