The Experts below are selected from a list of 145803 Experts worldwide ranked by ideXlab platform
Rudolf Valenta - One of the best experts on this subject based on the ideXlab platform.
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tolerization of a type i allergic immune response through transplantation of genetically modified hematopoietic stem Cells
Journal of Immunology, 2008Co-Authors: Ulrike Baranyi, Rudolf Valenta, Birgit Linhart, Nina Pilat, Martina Gattringer, Jessamyn Bagley, F Muehlbacher, John Iacomini, Thomas WekerleAbstract:Allergy represents a hypersensitivity disease that affects >25% of the population in industrialized countries. The underlying type I allergic immune reaction occurs in predisposed atopic individuals in response to otherwise harmless Ags (i.e., allergens) and is characterized by the production of allergen-specific IgE, an allergen-specific T Cell response, and the release of biologically active mediators such as histamine from mast Cells and basophils. Regimens permanently tolerizing an allergic immune response still need to be developed. We therefore retrovirally transduced murine hematopoietic stem Cells to express the major grass pollen allergen Phl p 5 on their Cell membrane. Transplantation of these genetically modified hematopoietic stem Cells led to durable multilineage molecular chimerism and permanent immunological tolerance toward the introduced allergen at the B Cell, T Cell, and Effector Cell levels. Notably, Phl p 5-specific serum IgE and IgG remained undetectable, and T Cell nonresponsiveness persisted throughout follow-up (40 wk). Besides, mediator release was specifically absent in in vitro and in vivo assays. B Cell, T Cell, and Effector Cell responses to an unrelated control allergen (Bet v 1) were unperturbed, demonstrating specificity of this tolerance protocol. We thus describe a novel Cell-based strategy for the prevention of allergy.
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recombinant allergen molecules tools to study Effector Cell activation
Immunological Reviews, 2001Co-Authors: Rudolf Valenta, D KraftAbstract:Summary: The IgE antibody-mediated activation of allergic Effector Cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect Effector Cell activation. If the structural requirements for Effector Cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects. The authors would like to thank Dr. Peter Valent, Department of Hematology, Vienna General Hospital, Austria, and Dr. Steven C. Almo, Department of Biochemistry, Albert Einstein College of Medicine, New York, USA, for fruitful collaboration regarding Effector Cell activation and structural biology, respectively. The skilful editorial assistance of Irmgard Lubelik is acknowledged. This work was supported by grant Y078 GEN of the Austrian Science Fund and by the ICP Program of the Austrian Federal Ministry for Education, Science and Culture.
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Recombinant allergen molecules: tools to study Effector Cell activation.
Immunological Reviews, 2001Co-Authors: Rudolf Valenta, D KraftAbstract:The IgE antibody-mediated activation of allergic Effector Cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect Effector Cell activation. If the structural requirements for Effector Cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.
D Kraft - One of the best experts on this subject based on the ideXlab platform.
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recombinant allergen molecules tools to study Effector Cell activation
Immunological Reviews, 2001Co-Authors: Rudolf Valenta, D KraftAbstract:Summary: The IgE antibody-mediated activation of allergic Effector Cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect Effector Cell activation. If the structural requirements for Effector Cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects. The authors would like to thank Dr. Peter Valent, Department of Hematology, Vienna General Hospital, Austria, and Dr. Steven C. Almo, Department of Biochemistry, Albert Einstein College of Medicine, New York, USA, for fruitful collaboration regarding Effector Cell activation and structural biology, respectively. The skilful editorial assistance of Irmgard Lubelik is acknowledged. This work was supported by grant Y078 GEN of the Austrian Science Fund and by the ICP Program of the Austrian Federal Ministry for Education, Science and Culture.
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Recombinant allergen molecules: tools to study Effector Cell activation.
Immunological Reviews, 2001Co-Authors: Rudolf Valenta, D KraftAbstract:The IgE antibody-mediated activation of allergic Effector Cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect Effector Cell activation. If the structural requirements for Effector Cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.
Harald Von Boehmer - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms of suppression by suppressor T Cells
Nature Immunology, 2005Co-Authors: Harald Von BoehmerAbstract:Mechanisms of immunosuppression by CD4^+CD25^+ suppressor T Cells have been addressed using many in vitro and in vivo conditions. However, those studies have not yielded a single mode of action. This review will discuss the mechanisms of suppression, which include the local secretion of cytokines such as TGF-β and direct Cell contact through binding of Cell surface molecules such as CTLA-4 on suppressor T Cells to CD80 and CD86 molecules on Effector T Cells. Suppression requires the appropriate colocalization of suppressor and Effector T Cells in different tissue and may involve the interference with T Cell receptor signaling that triggers transcription factors important in regulating Effector Cell function.
Johannes Tschoep - One of the best experts on this subject based on the ideXlab platform.
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il 7 promotes t Cell viability trafficking and functionality and improves survival in sepsis
Journal of Immunology, 2010Co-Authors: Jacqueline Unsinger, Margaret Mcglynn, Kevin R Kasten, Andrew S Hoekzema, Eizo Watanabe, Jared T Muenzer, Jacquelyn S Mcdonough, Johannes TschoepAbstract:Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune Cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune Effector Cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T Cells, restored IFN-γ production, and improved immune Effector Cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-γ– and T Cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis.
Lars Harder Christensen - One of the best experts on this subject based on the ideXlab platform.
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antibody repertoire complexity and Effector Cell biology determined by assays for ige mediated basophil and t Cell activation
Journal of Immunological Methods, 2012Co-Authors: G Lund, Nicholas Willumsen, Jens Holm, Lars Harder Christensen, P A Wurtzen, Kaare LundAbstract:Abstract Effector Cell activation and T-Cell activation, the latter mediated by facilitated antigen presentation, are immunological mechanisms that play crucial roles in the manifestation and maintenance of allergic disease. In addition to their relevance for the pathogenesis of allergy in-vivo, in-vitro assays based on these immunological mechanisms have been established and used for diagnostics, for monitoring the progression of disease and for the effect of specific immunotherapy as well as for basic research purposes. Here we review different parameters that affect Effector Cell activation and facilitated antigen uptake and presentation, including assay designs, readout parameters and critical experimental conditions. Central to the two immunological mechanisms is complex formation between allergen-specific IgE, allergen, and Cell surface-anchored immunoglobulin receptor; the high affinity IgE-receptor FceRI on basophils and mast Cells, and the low affinity IgE-receptor FceRII (CD23) on B-Cells. Accordingly, the effect of IgE repertoire complexity and allergen diversity on Effector Cell and facilitated antigen presentation is discussed in detail.
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several distinct properties of the ige repertoire determine Effector Cell degranulation in response to allergen challenge
The Journal of Allergy and Clinical Immunology, 2008Co-Authors: G Lund, Jens Holm, Lars Harder Christensen, Erik Riise, Kaare LundAbstract:Background On cross-linking of receptor-bound IgE antibodies by allergens, Effector Cells (basophils and mast Cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms. Objective We sought to investigate how individual properties of an IgE repertoire affect Effector Cell degranulation. Methods A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2. Results A total of 31 Der p 2–specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (K D value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non–allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality). Conclusion This study demonstrates how distinct properties of the IgE repertoire, such as total and allergen-specific IgE antibody concentration, IgE affinity, and IgE clonality, affect Effector Cell degranulation.
