Página 13 dos resultados de 15239 itens digitais encontrados em 0.006 segundos

‣ The Allergy and Immunology Milestone Project

Fonte: The Accreditation Council for Graduate Medical Education Publicador: The Accreditation Council for Graduate Medical Education
Tipo: Artigo de Revista Científica
Publicado em /03/2014 Português
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‣ Formulating the Allergy and Immunology Milestones

Nelson, Michael R.
Fonte: The Accreditation Council for Graduate Medical Education Publicador: The Accreditation Council for Graduate Medical Education
Tipo: Artigo de Revista Científica
Publicado em /03/2014 Português
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‣ HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology

Zhang, Guang Lan; Riemer, Angelika B.; Keskin, Derin B.; Chitkushev, Lou; Reinherz, Ellis L.; Brusic, Vladimir
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 04/04/2014 Português
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High-risk human papillomaviruses (HPVs) are the causes of many cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal. To facilitate diagnosis, prognosis and characterization of these cancers, it is necessary to make full use of the immunological data on HPV available through publications, technical reports and databases. These data vary in granularity, quality and complexity. The extraction of knowledge from the vast amount of immunological data using data mining techniques remains a challenging task. To support integration of data and knowledge in virology and vaccinology, we developed a framework called KB-builder to streamline the development and deployment of web-accessible immunological knowledge systems. The framework consists of seven major functional modules, each facilitating a specific aspect of the knowledgebase construction process. Using KB-builder, we constructed the Human Papillomavirus T cell Antigen Database (HPVdb). It contains 2781 curated antigen entries of antigenic proteins derived from 18 genotypes of high-risk HPV and 18 genotypes of low-risk HPV. The HPVdb also catalogs 191 verified T cell epitopes and 45 verified human leukocyte antigen (HLA) ligands. Primary amino acid sequences of HPV antigens were collected and annotated from the UniProtKB. T cell epitopes and HLA ligands were collected from data mining of scientific literature and databases. The data were subject to extensive quality control (redundancy elimination...

‣ Mouse Models to Study Dengue Virus Immunology and Pathogenesis

Zellweger, Raphaël M.; Shresta, Sujan
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 10/04/2014 Português
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The development of a compelling murine model of dengue virus (DENV) infection has been challenging, because DENV clinical isolates do not readily replicate or cause pathology in immunocompetent mice. However, research using immunocompromised mice and/or mouse-adapted viruses allows investigation of questions that may be impossible to address in human studies. In this review, we discuss the potential strengths and limitations of existing mouse models of dengue disease. Human studies are descriptive by nature; moreover, the strain, time, and sequence of infection are often unknown. In contrast, in mice, the conditions of infection are well defined and a large number of experimental parameters can be varied at will. Therefore, mouse models offer an opportunity to experimentally test hypotheses that are based on epidemiological observations. In particular, gain-of-function or loss-of-function models can be established to assess how different components of the immune system (either alone or in combination) contribute to protection or pathogenesis during secondary infections or after vaccination. In addition, mouse models have been used for pre-clinical testing of anti-viral drugs or for vaccine development studies. Conclusions based on mouse experiments must be extrapolated to DENV-infection in humans with caution due to the inherent limitations of animal models. However...

‣ Miniaturized and High-Throughput Assays for Analysis of T-Cell Immunity Specific for Opportunistic Pathogens and HIV

Li Pira, Giuseppina; Ivaldi, Federico; Starc, Nadia; Landi, Fabiola; Locatelli, Franco; Rutella, Sergio; Tripodi, Gino; Manca, Fabrizio
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2014 Português
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Monitoring of antigen-specific T-cell responses is valuable in numerous conditions that include infectious diseases, vaccinations, and opportunistic infections associated with acquired or congenital immune defects. A variety of assays that make use of peripheral lymphocytes to test activation markers, T-cell receptor expression, or functional responses are currently available. The last group of assays calls for large numbers of functional lymphocytes. The number of cells increases with the number of antigens to be tested. Consequently, cells may be the limiting factor, particularly in lymphopenic subjects and in children, the groups that more often require immune monitoring. We have developed immunochemical assays that measure secreted cytokines in the same wells in which peripheral blood mononuclear cells (PBMC) are cultured. This procedure lent itself to miniaturization and automation. Lymphoproliferation and the enzyme-linked immunosorbent spot (ELISPOT) assay have been adapted to a miniaturized format. Here we provide examples of immune profiles and describe a comparison between miniaturized assays based on cytokine secretion or proliferation. We also demonstrate that these assays are convenient for use in testing antigen specificity in established T-cell lines...

‣ Nod-Like Receptors: Key Molecular Switches in the Conundrum of Cancer

Kent, Andrew; Blander, J. Magarian
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 23/04/2014 Português
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It is believed the immune system can contribute to oncogenic transformation especially in settings of chronic inflammation, be activated during immunosurveillance to destroy early neoplastic cells before they undergo malignant outgrowth, and finally, can assist growth of established tumors by preventing clearance, remodeling surrounding tissue, and promoting metastatic events. These seemingly opposing roles of the immune system at the different stages of cancer development must all be mediated by innate signaling mechanisms that regulate the overall state of immune activation. Recently, the cytosolic nod-like receptor (NLR) pathway of innate immunity has gained a lot of attention in the tumor immunology field due to its known involvement in promoting inflammation and immunity, and conversely, in regulating tissue repair processes. In this review, we present all the current evidence for NLR involvement in the different stages of neoplasia to understand how a single molecular pathway can contribute to conflicting immunological interactions with cancer.

‣ Highlights of the advances in basic immunology in 2011

Liu, Juan; Liu, Shuxun; Cao, Xuetao
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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In this review, we summarize the major fundamental advances in immunological research reported in 2011. The highlights focus on the improved understanding of key questions in basic immunology, including the initiation and activation of innate responses as well as mechanisms for the development and function of various T-cell subsets. The research includes the identification of novel cytosolic RNA and DNA sensors as well as the identification of the novel regulators of the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway. Moreover, remarkable advances have been made in the developmental and functional properties of innate lymphoid cells (ILCs). Helper T cells and regulatory T (Treg) cells play indispensable roles in orchestrating adaptive immunity. There have been exciting discoveries regarding the regulatory mechanisms of the development of distinct T-cell subsets, particularly Th17 cells and Treg cells. The emerging roles of microRNAs (miRNAs) in T cell immunity are discussed, as is the recent identification of a novel T-cell subset referred to as follicular regulatory T (TFR) cells.

‣ Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

Lynge Nilsson, Line; Djurisic, Snezana; Hviid, Thomas Vauvert F.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 13/05/2014 Português
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In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class Ib protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unforeseen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact, its expression pattern is primarily limited to extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. It is these unique features that make HLA-G differ from its highly polymorphic HLA class Ia counterparts, the HLA-A, -B, and -C molecules. Its function, seemingly diverse, is typically receptor-mediated, and involves interactions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G plays an important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies...

‣ History of narcolepsy at Stanford University

Mignot, Emmanuel J. M.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Português
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Although narcolepsy was first described in the late nineteenth century in Germany and France, much of the research on this disorder has been conducted at Stanford University, starting with Drs. William C. Dement and Christian Guilleminault in the 1970s. The prevalence of narcolepsy was established, and a canine model discovered. Following the finding in Japan that almost all patients with narcolepsy carry a specific HLA subtype, HLA-DR2, Hugh Mac Devitt, F. Carl Grumet, and Larry Steinman initiated immunological studies, but results were generally negative. Using the narcoleptic canines, Dr. Nishino and I established that stimulants increased wakefulness by stimulating dopaminergic transmission while antidepressants suppress cataplexy via adrenergic reuptake inhibition. A linkage study was initiated with Dr. Grumet in 1988, and after 10 years of work, the canine narcolepsy gene was cloned by in 1999 and identified as the hypocretin (orexin) receptor 2. In 1992, studying African Americans, we also found that DQ0602 rather than DR2 was a better marker for narcolepsy across all ethnic groups. In 2000, Dr. Nishino and I, in collaboration with Dr. Lammers in the Netherlands, found that hypocretin 1 levels in the cerebrospinal fluid (CSF) were undetectable in most cases...

‣ Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer

Raval, Raju R; Sharabi, Andrew B; Walker, Amanda J; Drake, Charles G; Sharma, Padmanee
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 14/05/2014 Português
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Knowledge of the basic mechanisms of the immune system as it relates to cancer has been increasing rapidly. These developments have accelerated the translation of these advancements into medical breakthroughs for many cancer patients. The immune system is designed to discriminate between self and non-self, and through genetic recombination there is virtually no limit to the number of antigens it can recognize. Thus, mutational events, translocations, and other genetic abnormalities within cancer cells may be distinguished as “altered-self” and these differences may play an important role in preventing the development or progression of cancer. However, tumors may utilize a variety of mechanisms to evade the immune system as well. Cancer biologists are aiming to both better understand the relationship between tumors and the normal immune system, and to look for ways to alter the playing field for cancer immunotherapy. Summarized in this review are discussions from the 2013 SITC Primer, which focused on reviewing current knowledge and future directions of research related to tumor immunology and cancer immunotherapy, including sessions on innate immunity, adaptive immunity, therapeutic approaches (dendritic cells, adoptive T cell therapy...

‣ Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8+ T-Regulatory Cells that Suppress SIV-Positive CD4+ T-Cell Activation and Prevent SIV Infection in the Macaque Model

Andrieu, Jean-Marie; Chen, Song; Lai, Chunhui; Guo, Weizhong; Lu, Wei
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 30/06/2014 Português
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A new paradigm of mucosal vaccination against human immunodeficiency virus (HIV) infection has been investigated in the macaque model. A vaccine consisting of inactivated simian immunodeficiency virus (SIV)mac239 particles together with a living bacterial adjuvant (either the Calmette and Guerin bacillus, Lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastric route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8+ T-regulatory cells that suppressed the activation of SIV-positive CD4+ T-lymphocytes. SIV reverse transcription was thereby blocked in inactivated CD4+ T-cells; the initial burst of virus replication was prevented and the vaccinated macaques were protected from a challenge infection. For 3–14 months after intragastric immunization, 24 macaques were challenged intrarectally with a high dose of SIVmac239 or with the heterologous strain SIV B670 (both strains grown on macaques PBMC). Twenty-three of these animals were found to be protected for up to 48 months while all 24 control macaques became infected. This protective effect against SIV challenge together with the concomitant identification of a robust ex vivo correlate of protection suggests a new approach for developing an HIV vaccine in humans. The induction of this new class of CD8+ T-regulatory cells could also possibly be used therapeutically for suppressing HIV replication in infected patients and this novel tolerogenic vaccine paradigm may have potential applications for treating a wide range of immune disorders and is likely to may have profound implications across immunology generally.

‣ Big Data Analytics in Immunology: A Knowledge-Based Approach

Zhang, Guang Lan; Sun, Jing; Chitkushev, Lou; Brusic, Vladimir
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
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With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow.

‣ How advances in immunology provide insight into improving vaccine efficacy

Slifka, Mark K.; Amanna, Ian
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions...

‣ Advances in Swine Immunology Help Move Vaccine Technology Forward

Murtaugh, Michael P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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In veterinary animal species, vaccines are the primary tool for disease prevention, a key tool for treatment of infection, and essential for helping maintain animal welfare and productivity. Traditional vaccine development by trial-and-error has achieved many successes. However, effective vaccines that provide solid cross-protective immunity with excellent safety are still needed for many diseases. The path to development of vaccines against difficult pathogens requires recognition of uniquely evolved immunological interactions of individual animal hosts and their specific pathogens. Here, general principles that currently guide veterinary immunology and vaccinology research are reviewed, with an emphasis on examples from swine. Advances in genomics and proteomics now provide the community with powerful tools for elucidation of regulatory and effector mechanisms of protective immunity that provide new opportunities for successful translation of immunological discoveries into safe and effective vaccines.

‣ Progression of carcinogen‐induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics

Ondondo, Beatrice; Jones, Emma; Hindley, James; Cutting, Scott; Smart, Kathryn; Bridgeman, Hayley; Matthews, Katherine K.; Ladell, Kristin; Price, David A.; Jackson, David G.; Godkin, Andrew; Ager, Ann; Gallimore, Awen
Fonte: Wiley-Liss Publicador: Wiley-Liss
Tipo: Artigo de Revista Científica
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The tumor microenvironment comprises newly formed blood and lymphatic vessels which shape the influx, retention and departure of lymphocytes within the tumor mass. Thus, by influencing the intratumoral composition of lymphocytes, these vessels affect the manner in which the adaptive immune system responds to the tumor, either promoting or impairing effective antitumor immunity. In our study, we utilized a mouse model of carcinogen‐induced fibrosarcoma to examine the composition of tumor‐infiltrating lymphocytes during tumor progression. In particular, we sought to determine whether CD4+Foxp3+ regulatory T cells (Tregs) became enriched during tumor progression thereby contributing to tumor‐driven immunosuppression. This was not the case as the proportion of Tregs and effector CD4+ T cells actually declined within the tumor owing to the unexpected accumulation of naïve T cells. However, we found no evidence for antigen‐driven migration of these T cells or for their participation in an antitumor immune response. Our data support the notion that lymphocytes can enter tumors via aberrantly formed blood and lymphatic vessels. Such findings suggest that targeting both the tumor vasculature and lymphatics will alter the balance of lymphocyte subpopulations that enter the tumor mass. A consideration of this aspect of tumor immunology may be critical to the success of solid cancer immunotherapies.

‣ Democratizing Systems Immunology with Modular Transcriptional Repertoires Analyses

Chaussabel, Damien; Baldwin, Nicole
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/2014 Português
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Individual elements that constitute the immune system have been characterized over the past decades, largely through reductionist approaches. More recently the introduction of large-scale profiling platforms has enabled the assessment of these elements on a global scale. However, the analysis and interpretation of such large-scale data remains a challenge and a barrier for the wider adoption of systems approaches in immunological and clinical studies. Here, we describe an analytic strategy relying on the a priori determination of co-dependent gene sets for a given biological system. Such modular transcriptional repertoires can in turn be used to simplify the analysis and interpretation of large-scale datasets and to design targeted immune fingerprinting assays and web applications that will further facilitate the dissemination of systems approaches in immunology.

‣ Rethinking vector immunology: the role of environmental temperature in shaping resistance

Murdock, Courtney C.; Paaijmans, Krijn P.; Cox-Foster, Diana; Read, Andrew F.; Thomas, Matthew B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Recent ecological research has revealed that environmental factors can strongly affect insect immunity and influence the outcome of host–parasite interactions. To date, however, most studies examining immune function in mosquitoes have ignored environmental variability. We argue that one such environmental variable, temperature, influences both vector immunity and the parasite itself. As temperatures in the field can vary greatly from the ambient temperature in the laboratory, it will be essential to take temperature into account when studying vector immunology.

‣ Investigating the Effectiveness of an Educational Card Game for Learning How Human Immunology Is Regulated

Su, TzuFen; Cheng, Meng-Tzu; Lin, Shu-Hua
Fonte: American Society for Cell Biology Publicador: American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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This study is being conducted in an attempt to investigate the effectiveness of an educational card game we developed for learning about human immunology. The obtained results indicate that students did learn from the educational card game and generally had positive perceptions of the game-based instruction and its learning efficiency.

‣ The Aryl Hydrocarbon Receptor Meets Immunology: Friend or Foe? A Little of Both

Julliard, Walker; Fechner, John H.; Mezrich, Joshua D.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 02/10/2014 Português
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The aryl hydrocarbon receptor (AHR) has long been studied by toxicologists as a ligand-activated transcription factor that is activated by dioxin and other environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). The hallmark of AHR activation is the upregulation of the cytochrome P450 enzymes that metabolize many of these toxic compounds. However, recent findings demonstrate that both exogenous and endogenous AHR ligands can alter innate and adaptive immune responses including effects on T-cell differentiation. Kynurenine, a tryptophan breakdown product, is one such endogenous ligand of the AHR. Expression of indoleamine 2,3-dioxygenase by dendritic cells causes accumulation of kynurenine and results in subsequent tolerogenic effects including increased regulatory T-cell activity. At the same time, PAHs found in pollution enhance Th17 differentiation in the lungs of exposed mice via the AHR. In this perspective, we will discuss the importance of the AHR in the immune system and the role this might play in normal physiology and response to disease.

‣ Salmonella enterica in the Chicken: How it has Helped Our Understanding of Immunology in a Non-Biomedical Model Species

Wigley, Paul
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 10/10/2014 Português
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Salmonella infection of the chicken is important both as a source of foodborne human salmonellosis and as a source of disease in the chicken itself. Vaccination and other control strategies require an understanding of the immune response and as such have been important in understanding both mucosal immunity and more generally the response to bacterial infection. In this review, we discuss the contribution the study of avian salmonellosis has made to understanding innate immunity including the function of phagocytic cells, pattern recognition receptors, and defensins. The mucosal response to Salmonella infection and its regulation and the contribution this makes in protection against infection and persistence within the gut and future directions in better understanding the role of TH17 and Tregs in this response. Finally, we discuss the role of the immune system and its modulation in persistent infection and infection of the reproductive tract. We also outline key areas of research required to fully understand the interaction between the chicken immune system and Salmonella and how infection is maintained in the absence of substantive gastrointestinal disease.