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‣ Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding

Chappell, Paul E; Meziane, El Kahina; Harrison, Michael; Magiera, Łukasz; Hermann, Clemens; Mears, Laura; Wrobel, Antoni G; Durant, Charlotte; Nielsen, Lise Lotte; Buus, Søren; Ternette, Nicola; Mwangi, William; Butter, Colin; Nair, Venugopal; Ahyee, Tr
Fonte: eLife Sciences Publications, Ltd Publicador: eLife Sciences Publications, Ltd
Tipo: Artigo de Revista Científica
Publicado em 10/04/2015 Português
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Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.

‣ Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’

Simpson, Elizabeth
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em 19/04/2015 Português
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‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’, published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603–606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar...

‣ PKC-Theta in Regulatory and Effector T-cell Functions

Brezar, Vedran; Tu, Wen Juan; Seddiki, Nabila
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 13/10/2015 Português
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One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/off of robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-θ) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells. Recent studies demonstrated that major differences between Teffs and Tregs occurred at the IS where its formation induces altered signaling pathways in Tregs. These pathways are characterized by reduced recruitment of PKC-θ, suggesting that PKC-θ inhibits Tregs suppressive function in a negative feedback loop. As the balance of Teffs and Tregs has been shown to be central in several diseases, it was not surprising that some studies revealed that PKC-θ plays a major role in the regulation of this balance. This review will examine recent knowledge on the role of PKC-θ in T-cell transcriptional responses and how this protein can impact on the function of both Tregs and Teffs.

‣ Selection of Epstein-Barr virus specific cytotoxic T lymphocytes can be performed with B lymphoblastoid cell lines created in serum-free media

Gallot, G; Vollant, S; Vivien, R; Clémenceau, B; Ferrand, C; Tiberghien, P; Gaschet, J; Robillard, N; Vié, H
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2006 Português
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Epstein-Barr Virus (EBV)-transformed B lymphoblastoid cell lines (BLCL) are currently used for numerous applications in cellular immunology. Where protocols destined for clinical application are concerned, the final choice of assay is made according to a risk/benefit ratio analysis. In this balance the use of xenogenic or allogenic serum has always been a major concern, as it carries both an infectious and an immunological risk. So far, it is unknown whether serum can be omitted from the entire BLCL selection procedure. In addition, as BLCL have been described as heterogeneous, serum deprivation may affect their antigen-presenting capacity. In the present study, BLCL were generated in the absence or presence of fetal calf serum (referred to as BLCL0 or BLCLFCS, respectively). Next, in order to assess the antigen-presenting capacity of these cells, we compared the ability of BLCL0 and BLCLFCS cells to stimulate the EBV-specific repertoire of the corresponding donor's peripheral blood mononuclear cells in vitro. Our results showed that addition of serum was not essential for BLCL infection and culture, and that as far as we could determine, BLCL0 cells were as effective as BLCLFCS in reactivating the EBV-specific T-cell repertoire in vitro. Notably...

‣ Immunology of leishmaniasis*

Heyneman, D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //1971 Português
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Knowledge of the immunological basis of the leishmaniases and of the host's response is fragmentary and largely pragmatic. This paper reviews certain conceptual and clinical aspects of the immunology of these diseases. Consideration is given to man's natural resistance and his ability to acquire resistance from natural infections and from vaccination. The age-distribution of infection in different populations is discussed in relation to the effects that interaction between the parasite and its intermediate host may have on its infection characteristics and virulence.

‣ Clinical Immunology Review Series: An approach to the patient with allergy in childhood

Sporik, R; Henderson, J; Hourihane, J O'B
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2009 Português
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Allergic conditions are common, with asthma being the most common chronic illness in childhood in most developed countries. Some 80% of asthmatic children are sensitized to aeroallergens, usually indoor animal dander and house dust mite. Some 80% of asthmatics also have rhinitis. Rhinitis and eczema receive less medical attention than asthma, but they can cause long-term morbidity and have substantial direct and indirect economic costs. Food allergy and anaphylaxis are increasingly recognised and are usually easily diagnosed and managed. Clinicians can use in vivo and in vitro measurements of allergen-specific immunoglobulin E to better time reintroduction of implicated foods. Specific parenteral and sublingual immunotherapy is widely practiced internationally but is uncommon in the UK. It may alter the natural history of aeroallergen reactive diseases in the upper and lower airways. Specific oral tolerance induction represents the current cutting edge in clinical allergy research. It remands resource intensive at present and cannot be adopted into routine clinical practice at this time.

‣ Application of a Static Fluorescence-based Cytometer (the CellScan) in Basic Cytometric Studies, Clinical Pharmacology, Oncology and Clinical Immunology

Harel, Michal; Gilburd, Boris; Schiffenbauer, Yael S.; Shoenfeld, Yehuda
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em /09/2005 Português
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The CellScan apparatus is a laser scanning cytometer enabling repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. The CellScan may serve as a tool for diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) as well as other autoimmune diseases by monitoring FP changes in peripheral blood lymphocytes (PBLs) following exposure to autoantigenic stimuli. Changes in FI and FP in atherosclerotic patients' PBLs following exposure to various stimuli have established the role of the immune system in atherosclerotic disease. The CellScan has been evaluated as a diagnostic tool for drug-allergy, based on FP reduction in PBLs following incubation with allergenic drugs. FI and FP changes in cancer cells have been found to be well correlated with the cytotoxic effect of anti-neoplastic drugs. In conclusion, the CellScan has a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.

‣ Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

Entschladen, Frank; Altschmied, Joachim; Baumgrass, Ria; Behrmann, Iris; Giehl, Klaudia; Hermanns, Heike; Huber, Otmar; Kieser, Arnd; Klotz, Lars-Oliver; Kubatzky, Katharina F; Hass, Ralf; Janssen, Ottmar; Friedrich, Karlheinz
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 11/02/2010 Português
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The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of Düsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ). In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in Würzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference.

‣ Diagnosis of food allergies: the impact of oral food challenge testing

Ito, Komei
Fonte: Asia Pacific Association of Allergy, Asthma and Clinical Immunology Publicador: Asia Pacific Association of Allergy, Asthma and Clinical Immunology
Tipo: Artigo de Revista Científica
Português
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A diagnosis of food allergies should be made based on the observation of allergic symptoms following the intake of suspected foods and the presence of allergen-specific IgE antibodies. The oral food challenge (OFC) test is the most reliable clinical procedure for diagnosing food allergies. Specific IgE testing of allergen components as well as classical crude allergen extracts helps to make a more specific diagnosis of food allergies. The Japanese Society of Pediatric Allergy and Clinical Immunology issued the 'Japanese Pediatric Guideline for Food Allergy 2012' to provide information regarding the standardized diagnosis and management of food allergies. This review summarizes recent progress in the diagnosis of food allergies, focusing on the use of specific IgE tests and the OFC procedure in accordance with the Japanese guidelines.

‣ Immunology beats cancer: a blueprint for successful translation

Pardoll, Drew M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2012 Português
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Immunology offers an unprecedented opportunity for the science-driven development of therapeutics. The successes of antibodies to the immunomodulatory receptor CTLA-4 and blockade of the immunoinhibitory receptor PD-1 in cancer immunotherapy, from gene discovery to patient benefit, have created a paradigm for driving such endeavors.

‣ Alloreactive Regulatory T Cells Allow the Generation of Mixed Chimerism and Transplant Tolerance

Ruiz, Paulina; Maldonado, Paula; Hidalgo, Yessia; Sauma, Daniela; Rosemblatt, Mario; Bono, Maria Rosa
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 23/11/2015 Português
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The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant (NM-BMT) protocol using retinoic acid (RA)-induced alloantigen-specific Tregs, clinically available immunosuppressive drugs, and lower doses of irradiation. We demonstrate that RA-induced alloantigen-specific Tregs in addition to a NM-BMT protocol generates stable mixed chimerism and induces tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

‣ DNP-KLH Yields Changes in Leukocyte Populations and Immunoglobulin Isotype Use with Different Immunization Routes in Zebrafish

Weir, Heather; Chen, Patricia L.; Deiss, Thaddeus C.; Jacobs, Natalie; Nabity, Mary B.; Young, Matt; Criscitiello, Michael F.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 01/12/2015 Português
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Distinct methods are required for inducing mucosal versus systemic immunity in mammals for vaccine protection at the tissues most commonly breached by pathogens. Understanding of mucosal immunization in teleost fish is needed to combat aquaculture disease, understand emerging ecological threats, and know how vertebrate adaptive immunity evolved. Here, we quantitatively measured expression levels of IgM as well as the teleost mucosal immunoglobulin, IgZ/IgT, in zebrafish given an antigen systemically via intraperitoneal (i.p.) injection or mucosally via bath immersion. Both immunoglobulin isotypes and the B cell activating factor gene transcription was induced in fish injected with antigen as compared to saline injected or antigen immersed fish, though these failed to reach statistical significance. Here we provide additional reference hematology for this model species. Differential blood counts revealed a greater lymphocyte percentage in both i.p. and immersed fish, with increase in large lymphocyte counts and decrease in neutrophils. These humoral adaptive gene transcription and cytological data should provide a foundation for more studies connecting immunology in this dominant developmental and genetic fish model to other species where mucosal immunization is of greater commercial importance.

‣ Involvement of CD8+ T Cells in Multiple Sclerosis

Salou, Marion; Nicol, Bryan; Garcia, Alexandra; Laplaud, David-Axel
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 26/11/2015 Português
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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by focal demyelination patches associated with inflammatory infiltrates containing T lymphocytes. For decades, CD4+ T cells have been recognized as playing a major role in the disease, especially in animal models, which has led to the development of several therapies. However, interest has recently developed in the involvement of CD8+ T cells in MS following the analysis of infiltrating T cells in human brain lesions. A broad range of evidence now suggests that the pathological role of this T cell subset in MS may have been underestimated. In this review, we summarize the literature implicating CD8+ T cells in the pathophysiology of MS. We present data from studies in the fields of genetics, anatomopathology and immunology, mainly in humans but also in animal models of MS. Altogether, this strongly suggests that CD8+ T cells may be major effectors in the disease process, and that the development of treatments specifically targeting this subset would be germane.

‣ Teaming up against cancer : tumour immunology, immunotherapy and CARTs

Segura Garzón, Daniel
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: info:eu-repo/semantics/bachelorThesis; Text Formato: application/pdf
Publicado em //2014 Português
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‣ AIRE and Aire : a story about autoimmunity, APECED and immunology

Ortiz de Zugasti Carrón, Nilo
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: info:eu-repo/semantics/bachelorThesis; Text Formato: application/pdf
Publicado em //2013 Português
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‣ Immunology and the central nervous system

Barcia González, Carlos; Curtin, James; Zirger, Jeffrey; Larocque, Daniel
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: info:eu-repo/semantics/other; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em //2013 Português
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‣ Decision by committee: new light on the CD4/CD8-lineage choice

Rothenberg, Ellen V.
Fonte: Australasian Society for Immunology Publicador: Australasian Society for Immunology
Tipo: Article; PeerReviewed Formato: application/pdf
Publicado em /02/2009 Português
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The essence of a developmental decision is to convert a temporary difference between two cells, for example in their current exposure to environmental signals, into a long-term, irreversible difference in phenotype and function. For years, one of the most striking examples of this mechanism has been the choice of developing T cells between maturation in the CD4+ CD8- lineages or the CD4- CD8+ lineages, but the molecular mechanisms underpinning this decision have remained poorly understood. Three elegant studies published recently in Nature Immunology establish a sophisticated hierarchy of transcriptional regulators in which expression of triggering factors is followed by expression of enforcement factors, including Thpok and Runx3, to determine CD4/CD8-lineage choice.

‣ I. IMUNOLOGIA DA REPRODUÇÃO HUMANA; IMMUNOLOGY OF HUMAN REPRODUCTION

Souza, Sulani S.; Voltarelli, Júlio C.; Ferriani, Rui A.
Fonte: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto Publicador: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; Formato: application/pdf
Publicado em 30/06/1997 Português
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O sistema imunológico, com sua função tradicional de defender o organismo humano contra agressões externas e endógenas, é visto, hoje, num âmbito mais amplo de caráter homeostático. Assim, participa de vários mecanismos fisiológicos, dentre os quais se inclui a reprodução humana, onde tem importante papel desde a deposição dos espermatozóides até o nascimento do feto. Entretanto, pouco conhecimento é disponível a respeito da importância precisa do sistema imunológico nas várias etapas do processo reprodutivo. Nesta revisão, foram considerados vários aspectos imunológicos da reprodução humana e de quadros clínicos correlatos, como o aborto recorrente e a endometriose, além de estratégias terapêuticas, como a fertilização in vitro e a imunoterapia celular; The immunological system, which defends the human organism against external and endogenous aggression, is viewed today within a broader homeostatic role. This system also participates in various physiological mechanisms including the reproduction where it plays an important role from the deposition of sperm to the birth of the fetus. However, little is known about the precise importance of the immunological system during the various stages of the reproductive process. In the present review...

‣ Roles of Id3 and IL-13 in a Mouse Model of Autoimmune Exocrinopathy

Belle, Ian
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2015 Português
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Within the field of immunology, the existence of autoimmune diseases presents a unique set of challenges. The immune system typically protects the host by identifying foreign pathogens and mounting an appropriate response to eliminate them. Great strides have been made in understanding how foreign pathogens are identified and responded to, leading to the development of powerful immunological tools, such as vaccines and a myriad of models used to study infectious diseases and processes. However, it is occasionally possible for host tissues themselves to be inappropriately identified as foreign, prompting an immune response that attempts to eliminate the host tissue. The immune system has processes in place, referred to as selection, designed to prevent the development of cells capable of recognizing the self as foreign. While a great deal of work has been invested in understanding these processes, many concrete answers remain elusive.

Our laboratory, which focuses on understanding the roles of E and Id proteins in lymphocyte development, has established the Id3 knockout mouse as a model of autoimmune disease. Id3 knockout mice develop a disease reminiscent of human Sjӧgren's Syndrome, an autoimmune disease that progressively damages the salivary and lachrymal glands. Continued study of this model has yielded interesting results. These include the identification of CD4+ T cells as initiators of disease as well as the identification of the cytokine Interleukin 13 (IL-13) as a potential causative agent. However...

‣ Interactions of Mast Cells with the Lymphatic System: Delivery of Peripheral Signals to Lymph Nodes by Mast Cell-Derived Particles

Kunder, Christian
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 9868808 bytes; application/pdf
Publicado em //2009 Português
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Mast cells, best known for their pathologic role in allergy, have recently been shown to have key roles in the initiation of adaptive immune responses. These cells are located throughout the body just beneath barriers separating host from environment, possess multiple pathogen recognition systems, and store large quantities of fully active inflammatory mediators. These key features make them uniquely situated to act as sentinels of immunity, releasing the very earliest alarm signals when a pathogen is present. As a testament to the importance of these cells, mast cell-deficient mice have suboptimal immune responses, and mast cell activators can act as potent adjuvants for experimental immunizations. Specifically, mast cells have been shown to enhance the number of naive lymphocytes in infection site-draining lymph nodes, and to encourage the migration of dendritic cells to responding lymph nodes.

Although infections usually occur at peripheral sites, adaptive immune responses are initiated in distant lymph nodes. Despite the distance, signals from the site of infection result in dramatic, rapid reorganization of the node, including massive recruitment of naive lymphocytes from the circulation and extensive vascular restructuring to accommodate the increase in size. How such signals reach the lymph node is not well understood.

When mast cells degranulate...