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‣ Principles of ecological immunology

Sadd, Ben M; Schmid-Hempel, Paul
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
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Defending self against nonself is a major problem in a world in which individuals are under constant pressure from parasites that gain fitness benefits at a cost to their host. Defences that have evolved are diverse, and range from behavioural adaptations to physiochemical barriers. The immune defence is a final line of protection and is therefore of great importance. Given this importance, variability in immune defence would seem counterintuitive, yet that is what is observed. Ecological immunology attempts to explain this variation by invoking costs and trade-offs, and in turn proposing that the optimal immune defence will vary over environments. Studies in this field have been highly successful in establishing an evolutionary ecology framework around immunology. However, in order enrich our understanding of this area, it is perhaps time to broaden the focus to include parasites as more than simply elicitors of immune responses. In essence, to view immunity as produced by the host, the environment, and the active involvement of parasites.

‣ Systems immunology of human malaria

Tran, Tuan M.; Samal, Babru; Kirkness, Ewen; Crompton, Peter D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Plasmodium falciparum malaria remains a global public health threat. Optimism that a highly effective malaria vaccine can be developed stems in part from the observation that humans can acquire immunity to malaria through experimental and natural P. falciparum infection. Recent advances in systems immunology could accelerate efforts to unravel the mechanisms of acquired immunity to malaria. Here we review the tools of systems immunology, their current limitations in the context of human malaria research, and the human ‘models’ of malaria immunity to which these tools can be applied.

‣ A new take on comparative immunology; Relevance to immunotherapy

Wang, Ena; Albini, Adriana; Stroncek, David F; Marincola, Francesco M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/2009 Português
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It is becoming increasingly recognized that experimental animal models, while useful to address monothematic biological questions, bear unpredictable relevance to human disease. Several reasons have been proposed. However, the uncontrollable nature of human genetics and the heterogeneity of disease that with difficulty can be replicated experimentally play a leading role. Comparative immunology is a term that generally refers to the analysis of shared or diverging facets of immunology among species; these comparisons are carried according to the principle that evolutionarily conserved themes outline biologic functions universally relevant for survival. We propose that a similar strategy could be applied searching for themes shared by distinct immune pathologies within our own species. Identification of common patterns may outline pathways necessary for a particular determinism to occur such as tissue-specific rejection or tolerance. This approach is founded on the unproven but sensible presumption that Nature does not require an infinite plethora of redundant mechanisms to reach its purposes. Thus, immune pathologies must follow, at least in part, common means that determine their onset and maintenance. Commonalities among diseases can...

‣ Is interferon-gamma the right marker for bacille Calmette–Guérin-induced immune protection? The missing link in our understanding of tuberculosis immunology

Abebe, F
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /09/2012 Português
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Bacille Calmette–Guérin (BCG), developed a century ago, is the only licensed tuberculosis (TB) vaccine in use to date. The protective efficacy of BCG against TB varies with no apparent protection in some population, and mechanisms of its immune protection is poorly known, and yet BCG is the most widely used vaccine, with more than 4 billion BCG-vaccinated children globally. BCG is probably the only licensed vaccine currently in use believed to mediate immune protection through the production of interferon (IFN)-γ by CD4 T cells, which in turn activates macrophages to kill Mycobacterium tuberculosis (Mtb). Currently, a number of new TB candidate vaccines are in different phases of clinical trial. The majority of these new vaccines are either recombinant forms of BCG or prime boosters of BCG (rBCG) and their immunogenicity is tested using BCG as a benchmark by measuring specific IFN-γ produced by CD4+ T cells as a protective immune marker. However, some recent studies that examined mechanisms of immune protection of BCG in animals and humans have reported a lack of correlation between IFN-γ production by CD4 cells and BCG-induced immune protection. These studies point to the fact that there is a missing link in our understanding of TB immunology. Conversely...

‣ Bioinformatics for cancer immunology and immunotherapy

Charoentong, Pornpimol; Angelova, Mihaela; Efremova, Mirjana; Gallasch, Ralf; Hackl, Hubert; Galon, Jerome; Trajanoski, Zlatko
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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Recent mechanistic insights obtained from preclinical studies and the approval of the first immunotherapies has motivated increasing number of academic investigators and pharmaceutical/biotech companies to further elucidate the role of immunity in tumor pathogenesis and to reconsider the role of immunotherapy. Additionally, technological advances (e.g., next-generation sequencing) are providing unprecedented opportunities to draw a comprehensive picture of the tumor genomics landscape and ultimately enable individualized treatment. However, the increasing complexity of the generated data and the plethora of bioinformatics methods and tools pose considerable challenges to both tumor immunologists and clinical oncologists. In this review, we describe current concepts and future challenges for the management and analysis of data for cancer immunology and immunotherapy. We first highlight publicly available databases with specific focus on cancer immunology including databases for somatic mutations and epitope databases. We then give an overview of the bioinformatics methods for the analysis of next-generation sequencing data (whole-genome and exome sequencing), epitope prediction tools as well as methods for integrative data analysis and network modeling. Mathematical models are powerful tools that can predict and explain important patterns in the genetic and clinical progression of cancer. Therefore...

‣ Immunology primer for neurosurgeons and neurologists part I: Basic principles of immunology

Blaylock, Russell L.
Fonte: Medknow Publications & Media Pvt Ltd Publicador: Medknow Publications & Media Pvt Ltd
Tipo: Artigo de Revista Científica
Publicado em 28/01/2013 Português
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Our knowledge concerning the workings of the immune system has evolved considerably over the past 20 years, with great strides being made as regard to complex interactions and repertoire of effector reactions under a host of conditions. Many of our previous understandings have been challenged, especially concerning tumor immunology and autoimmunity. Also of critical importance is our understanding of how the immune system terminates its attacks and the mechanisms used to regulate the balance between proinflammatory and antiinflammatory mechanisms, so as to prevent excessive immune bystander damage. I will discuss in part I the basic physiology of innate immune function and the immune systems reactions to invasion by microorganisms.

‣ Human systems immunology: hypothesis-based modeling and unbiased data-driven approaches

Arazi, Arnon; Pendergraft, William F.; Ribeiro, Ruy M.; Perelson, Alan S.; Hacohen, Nir
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Systems immunology is an emerging paradigm that aims at a more systematic and quantitative understanding of the immune system. Two major approaches have been utilized to date in this field: unbiased data-driven modeling to comprehensively identify molecular and cellular components of a system and their interactions; and hypothesis-based quantitative modeling to understand the operating principles of a system by extracting a minimal set of variables and rules underlying them. In this review, we describe applications of the two approaches to the study of viral infections and autoimmune diseases in humans, and discuss possible ways by which these two approaches can synergize when applied to human immunology.

‣ Essential concept of transplant immunology for clinical practice

Kumbala, Damodar; Zhang, Rubin
Fonte: Baishideng Publishing Group Co., Limited Publicador: Baishideng Publishing Group Co., Limited
Tipo: Artigo de Revista Científica
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Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies (DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.

‣ Meeting Report: Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances

Keenan, Bridget P.; Jaffee, Elizabeth M.; Armstrong, Todd D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/2013 Português
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The fourth AACR Special Conference “Tumor Immunology: Basic and Clinical Advances” was held in Miami, Florida in November 2012. The overall objective of this meeting was to discuss emerging concepts in cancer immunology and immunotherapy. The key findings that emerged from this meeting included: 1) multiple immune checkpoints should be inhibited to increase effective T cell therapy, 2) successful adoptive T cell therapy will rely on obtaining the proper T cell phenotype, 3) chimeric antigen receptors have shown promise in treating some B cell malignancies, and 4) multiple pathways of inflammation within the tumor microenvironment are immunotherapy targets.

‣ Koch Institute Symposium on Cancer Immunology and Immunotherapy

Drake, Adam; Joshi, Nikhil S.; Szeto, Gregory L; Zhu, Eric; Eisen, Herman N.; Irvine, Darrell J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2013 Português
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The 12th annual summer symposium of The Koch Institute for Integrative Cancer Research at MIT was held in Cambridge, MA, on June 14th, 1023. The symposium entitled “Cancer Immunology and Immunotherapy” focused on recent advances in preclinical research in basic immunology and biomedical engineering, and their clinical application in cancer therapies. The day-long gathering also provided a forum for discussion and potential collaborations between engineers and clinical investigators. The major topics presented include: (i) enhancement of adoptive cell therapy by engineering to improve the ability and functionality of T-cells against tumor cells; (ii) current therapies using protein and antibody therapeutics to modulate endogenous anti-tumor immunity; and (iii) new technologies to identify molecular targets and assess therapeutic efficacy, and devices to control and target drug delivery more effectively and efficiently.

‣ Alcohol and immunology: Summary of the 2012 Alcohol and Immunology Research Interest Group (AIRIG) meeting

Ippolito, Jill A.; Curtis, Brenda J.; Choudhry, Mashkoor A.; Kovacs, Elizabeth J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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On October 27, 2012, the 17th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the Grand Wailea Hotel in Maui, Hawaii as a satellite meeting to the 2012 Society of Leukocyte Biology conference. This year’s meeting focused on the influence of alcohol on signal transduction pathways in various disease and injury models. Three plenary sessions were held where invited speakers shared their research on alcohol-mediated alterations of cell signaling components, immune cell subsets, and inflammation. These studies suggested alcohol has a negative effect on cell signaling machinery and immune cell homeostasis, resulting in disease, disease progression, and increased mortality. Researchers also identified tissue-specific alcohol-linked elevations in markers of inflammation, including cold-shock proteins and microRNAs. Additionally, one study revealed the effects of alcohol on immune cell subsets in a model of allergic asthma.

‣ Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology☆

Barker, Charlotte I.S.; Germovsek, Eva; Hoare, Rollo L.; Lestner, Jodi M.; Lewis, Joanna; Standing, Joseph F.
Fonte: Elsevier Science Publishers, B.V Publicador: Elsevier Science Publishers, B.V
Tipo: Artigo de Revista Científica
Publicado em 30/06/2014 Português
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Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose–concentration–effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.

‣ Reproductive Immunology Research: A Tight Interaction between Diverse Scientific and Clinical Disciplines Including Immunology, Obstetrics, Hematology, and Endocrinology

Giaglis, Stavros; Hahn, Sinuhe
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 23/01/2015 Português
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‣ Murine nematode immunology in Australasia

Dent, L.
Fonte: Blackwell Science Ltd Publicador: Blackwell Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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A relatively small number of laboratories in Australia and New Zealand have consistently published on murine models of nematode immunology, and the parasite species principally used are Heligmosomoides bakeri (previously Heligmosomoides polygyrus), Strongyloides ratti, Nippostrongylus brasiliensis and Toxocara canis. These research groups have made significant contributions to both fundamental immunology and more specialized issues in host–parasite relationships. Topics addressed include immune regulation, including the expression and control of Type 2 cytokines and the responses induced, innate and adaptive host-protective mechanisms, antigen expression and immune evasion strategies utilized by parasitic helminths. This review addresses the last 30 years of research and identifies areas in which major progress can be made, given appropriate resources.; L. A. Dent

‣ Computational Immunology : from MHC-peptide Binding to Immunotherapy; Computational Immunology : von MHC-Peptid Bindung zur Immuntherapie

Dönnes, Pierre
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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The human immune system provides effective protection against invading pathogens and cancer. Soluble antibodies can directly bind to extracellular antigens, whereas other mechanisms are needed for the recognition of virally infected or cancerous cells. Intracellular proteins are digested into smaller peptides, which are then displayed on the cell surface bound to major histocompatibility (MHC) class I molecules. Cytotoxic T (Tc) cells play an important role in the immune system since they can recognize MHC-peptide complexes and eliminate infected or abnormal cells. The intracellular events leading to MHC-peptide presentation are collectively known as antigen processing. There are three main steps in the antigen processing pathway; digestion of proteins into peptides by proteasomes in the cytosol, transport of peptides into the endoplasmic reticulum (ER) by the transporters associated with antigen processing (TAP), and MHC-peptide complex formation. A detailed understanding of these processes is a prerequisite for rational peptide vaccine design aiming to efficiently activate Tc cells. This has motivated the development of computational methods dealing with the different steps of the antigen processing pathway. Methods predicting MHC-peptide binding with relatively good accuracy exists...

‣ Los conceptos inmunol??gicos en los libros de texto: los cambios curriculares de la reforma

Azuaga Fortes, Mar??a Jos??
Fonte: Universidad de Granada Publicador: Universidad de Granada
Tipo: Artigo de Revista Científica
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La inmunolog??a y los conceptos relacionados son contenidos de creciente actualidad en la vida cotidiana de los seres humanos. Sin embargo, el peso curricular de los mismos ha sido tradicionalmente muy peque??o. El Dise??o Curricular Base de la Educaci??n Secundaria Obligatoria hizo ya alguna inclusi??n de estos contenidos, pero es el Real Decreto 3473/2000 sobre las Ense??anzas M??nimas para la Educaci??n Secundar??a Obligatoria el que marca con claridad un cambio m??s significativo. En este trabajo se analiza si los libros de texto anteriores y posteriores a este Real Decreto se hacen eco de dicho cambio.; The immunology and related concepts are of increasing interest in the daily life of human beings. However, the presence of the immunology concepts in the ???curricula??? has been traditionally very small. Some of these concepts were already included in the Basic Curricula Design of the Compulsory Secondary Education but the most significant change is in the Royal Decree 3473/2000, about Minimal Teaching for the Compulsary Secondary Education. In this paper we analyse if these changes are taken into account in textbooks published before and subsequent to the Royal Decree.

‣ ROLE OF MULTIPLE TOLL-LIKE RECEPTOR ACTIVATION IN REGULATING CYTOTOXIC T CELL PRIMING TO LYMPOCYTIC CHORIOMENINGITIS VIRUS INFECTIONS

SIDDIQUI, Sarah
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
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Foreign pathogens are recognized by toll-like receptors (TLR), present on various immune cells such as professional antigen-presenting cells (pAPCs). On recognition of its ligand, these receptors activate pAPCs, which may in turn influence naïve CD8+ T cell activation and affect their abilities to clear viral infection. However, how TLR ligands (TLR-L) can regulate CD8+ T cell responses have not been fully elucidated. This thesis will focus on examining how the presence of components from foreign pathogens, e.g. viral or bacterial infection, can contribute to shaping host immunity during concurrent viral infections. Since nitric oxide (NO), an innate effector immune molecule, was recently suggested to regulate proteasome activity; we sought to examine if NO can influence MHC-I antigen presentation during viral infections. The data in this section of the thesis provides evidence that combined TLR engagement can alter the presentation of certain CD8+ epitopes due to NO-induced inhibition in proteasome activity. Taken together, the data demonstrate that TLR ligation can influence the adaptive immune response due to induction of specific innate effector molecules such as NO. Next, the influence of combined TLR engagement on CD8+ T cell immunodominance hierarchies during viral infections was examined. In this section...

‣ Étude des facteurs influençant la susceptibilité à l'infection au VIH chez des femmes africaines

Lajoie, Julie
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
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Chez la femme, la majorité des cas d’infection au VIH sont acquis lors de relations hétérosexuelles. Cependant, très peu d’informations sont disponibles concernant l’immunité locale naturelle du tractus génital féminin, les facteurs influençant la susceptibilité à l’infection au VIH dans ce compartiment, ainsi que la réponse immunitaire de la muqueuse enclenchée après l’infection. Le but de notre projet est donc d’étudier certains facteurs pouvant être impliqués dans la susceptibilité à l’infection au VIH, afin de mieux comprendre l’immunité du tractus génital féminin. Nous avons, dans un premier temps, analysé le rôle du polymorphisme des gènes HLA-G et HLA-E sur la susceptibilité au VIH dans une population de femmes zimbabwéennes. La présence de l’allèle HLA-G*0105N, en combinaison avec le génotype HLA-EG/HLA-EG, était associée avec une diminution du risque d’infection. Puis, dans une étude cas-contrôle de travailleuses du sexe (TS) du Bénin, nous avons mesuré l’expression de HLA-G soluble au niveau du plasma. Nous avons observé une différence significative dans l’expression de HLA-G soluble, celle-ci étant plus faible dans le groupe des TS VIH positives comparé aux groupes de TS VIH négatives et de femmes VIH négatives de la population générale. Nous avons aussi analysé l’expression de cytokines et chimiokines dans le sérum et le tractus génital des participantes de l’étude du Bénin. Nous avons constaté que chez les TS VIH positives il y avait une expression plus élevée des chimiokines MPC-3...

‣ A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

Bocharov, Gennady; Züst, Roland; Cervantes-Barragan, Luisa; Luzyanina, Tatyana; Chiglintsev, Egor; Chereshnev, Valery A.; Thiel, Volker; Ludewig, Burkhard
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 103 to 104 Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However...

‣ What's New in Immunology?

Armstrong, W. D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1975 Português
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Since 1950, immunology has developed with such rapidity as an interdisciplinary science that even those within the field have difficulty keeping adequately informed. For this reason it is important that those who are closer to the subject, wherever possible, apply recent advances to the practice of medicine in general and primary care in particular. This paper describes a limited number of recent advances in the field of cellular immunology and immunodeficiency diseases. Above all, it attempts to relate the practical significance of these discoveries to the care of the patient by the primary care physician.