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Toll-Like Receptor Activation in Immunity vs. Tolerance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196364 Year: Pages: 75 DOI: 10.3389/978-2-88919-636-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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The innate immune system has evolved means to recognize and react suitably to foreign entities such as infectious agents. In many cases infectious microorganisms threaten the integrity and function of the target organs or tissues; therefore, consequent to their recognition the immune system becomes activated to ensure their elimination. Toll-like receptors (TLR) constitute a family of receptors specialized in the recognition of molecular patterns typically associated with infectious agents. Different TLRs exist, each selective for molecular entities and motifs belonging to a specific pathogen group. Consequently, it is thought that the molecular nature of invading microorganisms activates specific TLRs to drive adequate anti-infectious immunity. For instance, nucleic acid-specific, intracellular receptors (TLR3/7/8/9) are used to sense viruses and drive antiviral immunity, while other receptors (such as TLR2 and TLR4) recognize and promote immunity against bacteria, yeast, and fungi. Yet, it is becoming evident that activation of TLR pathways trigger mechanisms that not only stimulate but also regulate the immune system. For instance, TLR stimulation by viruses will drive antiviral interferon but also immunoregulatory cytokine production and regulatory T cell activation. Stimulation of TLRs by bacteria or using molecular agonists can also trigger both immune stimulatory and regulatory responses. TLR stimulation by infectious agents likely serves to activate but also control anti-infectious immunity, for instance prevent potential immunopathological tissue damage which can be caused by acute immune defense mechanisms. Previous work by us and others has shown that the immunoregulatory arm of TLR stimulation can additionally help control autoreactive processes in autoimmune disease. Hence, it is becoming established that gut commensals, which also play a crucial part in the control of autoimmune disease, establish immune regulatory mechanisms through activation of particular TLRs. In sum, it appears that TLRs are key immune players that not only stimulate but also regulate immune processes in health and disease. In this Research Topic, we wish to review the dual role of TLRs as activators and regulators of immune responses. We aim to motivate data-driven opinions as to the importance of context of TLR agonism for determining immune activation vs. regulation. The presentation of ongoing original works, as well as data and opinions around other innate immune receptors pertaining to this topic, are also encouraged.

Thymic stromal alterations and genetic disorders of immune system

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197170 Year: Pages: 81 DOI: 10.3389/978-2-88919-717-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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The pathogenic mechanisms underlying primary T-cell disorders are mainly related to molecular alterations of genes whose expression is intrinsic to hematopoietic cells. However, since the differentiation process requires a crosstalk among thymocytes and the thymic microenvironment, molecular alterations of genes, involved in the differentiation and functionality of the stromal component of the thymus, may lead to a severe T-cell defect or failure of central tolerance, as well. The first example of severe combined immunodeficiency (SCID) not related to an intrinsic alteration of the hematopoietic cell but rather of the thymic epithelial component is the Nude/SCID phenotype, inherited as an autosomal recessive disorder, whose hallmarks are the T-cell defect and the absence of the thymus. The clinical and immunological phenotype is the human equivalent of the murine Nude/SCID syndrome, which represents the first spontaneous SCID identified in nude mice in 1966. For over 3 decades studies of immune system in these mice enormously contributed to the overall knowledge of cell mediated immunity, in the assumption that the athymia of these mice was solely responsible for the T-cell immunological defect. This syndrome is due to mutations of the transcription factor FOXN1, belonging to the forkhead-box gene family, which is mainly expressed in the thymus and skin epithelial cells, where it plays a critical role in differentiation and survival. An alteration of the thymic structure is also a feature of the DiGeorge syndrome (DGS), which has been long considered the human counterpart of the nude mice phenotype. This syndrome is frequently associated to a deletion of the 22q11 region, which contains approximately 30 genes, including the TBX1 gene, which is responsible for most of the clinical features of DGS in humans and mice. In this syndrome common manifestations are cardiac malformations, speech delay, hypoparathyrodism and immunodeficiency, even though the immunological hallmarks of the T-cell defect in DiGeorge syndrome are profoundly different from those reported in human Nude/SCID. The divergence of the phenotype among these 2 entities raised the possibility that the FOXN1 transcription factor represents the real key stromal molecule implicated in directing the hematopoietic stem cell toward a proper T-cell fate. Thymic stromal component of the primary lymphoid organ is also required to negatively select the autoreactive clones, a process driven by the expression of tissue specific antigens (TSA) by medullary thymic epithelial cells (mTECs). The expression of genes encoding TSA antigens is mediated by autoimmune regulator (AIRE) gene, encoding a transcription factor expressed in mTECs. Molecular alterations of this gene are associated to autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a rare autosomal disorder, which may be considered the prototype of an autoimmune disease due to the failure of central tolerance homeostasis. All these "experiments of nature" led to unravel novel pathogenic mechanisms underlying inherited disorders of immune system and, of note, to clarify the pivotal role of epithelial cells in the maturation and education process of T-cell precursors.

Du sordide au mythe

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ISBN: 9782874631795 9782875581747 Year: Language: French
Publisher: Presses universitaires de Louvain
Added to DOAB on : 2017-05-12 11:12:22
License: OpenEdition licence for Books

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À la fin du XIXe siècle, Bruxelles est secouée par un scandale révélant la présence de mineures anglaises dans les maisons closes de la capitale. En cascade, les répercussions de l’« affaire de la traite des blanches » sont immédiates (campagnes médiatiques, enquêtes, séries de procès). À bien des égards, l’histoire des « petites anglaises » fait aussi l’effet d’un véritable détonateur : elle déliera les imaginaires et déchaînera les passions sur la fameuse question de la « traite des blanche...

ROS Regulation during Plant Abiotic Stress Responses

Authors: --- --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450541 Year: Pages: 306 DOI: 10.3389/978-2-88945-054-1 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Plants are continuously exposed to a wide range of environmental conditions, including cold, drought, salt, heat, which have major impact on plant growth and development. To survive, plants have evolved complex physiological and biochemical adaptations to cope with a variety of adverse environmental stresses. Among them, reactive oxygen species (ROS) are key regulators and play pivotal roles during plant stress responses, which are thought to function as early signals during plant abiotic stress responses. ROS were long regarded as unwanted and toxic by-products of physiological metabolism. However, ROS are now recognized as central players in the complex signaling network of cells. Therefore, a fine-tuning control between ROS production and scavenging pathways is essential to maintain non-toxic levels in planta under stressful conditions through enzymatic and non-enzymatic antioxidant defense systems. We focus on the roles of ROS during plant abiotic stress responses in this Research Topic. Plant responses to multiple abiotic stresses and effects of hormones and chemicals on plant stress responses have been carefully studies. Although functions of several stress responsive genes have been characterized and possible interactions between hormones and ROS are discussed, future researches are needed to functionally characterize ROS regulatory and signaling transduction pathways.Plants are continuously exposed to a wide range of environmental conditions, including cold, drought, salt, heat, which have major impact on plant growth and development. To survive, plants have evolved complex physiological and biochemical adaptations to cope with a variety of adverse environmental stresses. Among them, reactive oxygen species (ROS) are key regulators and play pivotal roles during plant stress responses, which are thought to function as early signals during plant abiotic stress responses. ROS were long regarded as unwanted and toxic by-products of physiological metabolism. However, ROS are now recognized as central players in the complex signaling network of cells. Therefore, a fine-tuning control between ROS production and scavenging pathways is essential to maintain non-toxic levels in planta under stressful conditions through enzymatic and non-enzymatic antioxidant defense systems. We focus on the roles of ROS during plant abiotic stress responses in this Research Topic. Plant responses to multiple abiotic stresses and effects of hormones and chemicals on plant stress responses have been carefully studies. Although functions of several stress responsive genes have been characterized and possible interactions between hormones and ROS are discussed, future researches are needed to functionally characterize ROS regulatory and signaling transduction pathways.

HLA-G-mediated Immune Tolerance: Past and New Outlooks

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451197 Year: Pages: 92 DOI: 10.3389/978-2-88945-119-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-07-06 13:27:36
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The non-classical HLA class I molecule HLA-G is different from classical HLA class I molecules because of the low polymorphism in the coding region, the fact that HLA-G primary transcript is alternatively spliced in seven isoforms, and the inhibitory action on immune cells. Although HLA-G is low polymorphic, variants in both promoter and 3’ un-translated region (UTR) of HLA-G locus regulate its expression. In healthy conditions, a basal level of HLA-G gene transcription is observed in most cells and tissues; however, translation into HLA-G protein is restricted to trophoblasts in the placenta, where it participates in promoting tolerance at the fetal-maternal interface. HLA-G is also expressed by thymic epitelial, cornea, mesenchymal stem cells, nail matrix, pancreatic beta cells, erythroid, and endothelial precursors. HLA-G can be neo-expressed in adult tissues in pathological conditions, and its expression has been documented autoimmune disorders, viral infections, and cancer. In the latter setting de novo HLA-G expression is associated with the capability of tumor cells to evade the immune control. In the last decade it has become evident that HLA-G expression on T cells and antigenpresenting cells confers to these cells tolerogenic properties. This Research Topic focused on i) summarizing updated clinical and immunological evidences that HLA-G expression is associate with beneficial or detrimental tolerance, ii) gathering new insights into the mechanisms governing the expression of HLA-G in healthy and pathological conditions, such as pre-eclampsia, and iii) examining the mechanisms underlying HLA-G mediated tolerance.

Genomic Approaches for Improvement of Understudied Grasses

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452422 Year: Pages: 165 DOI: 10.3389/978-2-88945-242-2 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Grasses are diverse, spanning native prairies to high-yielding grain cropping systems. They are valued for their beauty and useful for soil stabilization, pollution mitigation, biofuel production, nutritional value, and forage quality; grasses encompass the most important grain crops in the world. There are thousands of distinct grass species and many have promiscuous hybridization patterns, blurring species boundaries. Resources for advancing the science and knowledgebase of individual grass species or their unique characteristics varies, often proportional to their perceived value to society. For many grasses, limited genetic information hinders research progress. Presented in this research topic is a brief snapshot of creative efforts to apply modern genomics research methodologies to the study of several minor grass species.

Plant Responses to Biotic and Abiotic Stresses: Lessons from Cell Signaling

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453566 Year: Pages: 298 DOI: 10.3389/978-2-88945-356-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany --- Physiology
Added to DOAB on : 2018-02-27 16:16:45
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Facing stressful conditions imposed by their environment and affecting their growth and their development throughout their life cycle, plants must be able to perceive, to process and to translate different stimuli into adaptive responses. Understanding the organism-coordinated responses involves a fine description of the mechanisms occurring at the cellular and molecular level. A major challenge is also to understand how the large diversity of molecules identified as signals, sensors or effectors could drive a cell to the appropriate plant response and to finally cope with various environmental cues. In this Research Topic we aim to provide an overview of various signaling mechanisms or to present new molecular signals involved in stress response and to demonstrate how basic/fundamental research on cell signaling will help to understand stress responses at the whole plant level.

Salinity Tolerance in Plants: Mechanisms and Regulation of Ion Transport

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453696 Year: Pages: 243 DOI: 10.3389/978-2-88945-369-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2018-02-27 16:16:45
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Life presumably arose in the primeval oceans with similar or even greater salinity than the present ocean, so the ancient cells were designed to withstand salinity. However, the immediate ancestors of land plants most likely lived in fresh, or slightly brackish, water. The fresh/brackish water origins might explain why many land plants, including some cereals, can withstand moderate salinity, but only 1 – 2 % of all the higher plant species were able to re-discover their saline origins again and survive at increased salinities close to that of seawater. From a practical side, salinity is among the major threats to agriculture, having been one of the reasons for the demise of the ancient Mesopotamian Sumer civilisation and in the present time causing huge annual economic losses of over 10 billion USD. The effects of salinity on plants include osmotic stress, disruption of membrane ion transport, direct toxicity of high cytoplasmic concentrations of sodium and chloride on cellular processes and induced oxidative stress. Ion transport is the crucial starting point that determines salinity tolerance in plants. Transport via membranes is mediated mostly by the ion channels and transporters, which ensure selective passage of specific ions. The molecular and structural diversity of these ion channels and transporters is amazing. Obtaining the detailed descriptions of distinct ion channels and transporters present in halophytes, marine algae and salt-tolerant fungi and then progressing to the cellular and the whole organism mechanisms, is one of the logical ways to understand high salinity tolerance. Transfer of the genes from halophytes to agricultural crops is a means to increase salt tolerance of the crops. The theoretical scientific approaches involve protein chemistry, structure-function relations of membrane proteins, synthetic biology, systems biology and physiology of stress and ion homeostasis. At the time of compiling this e-book many aspects of ion transport under salinity stress are not yet well understood. The e-book has attracted researchers in ion transport and salinity tolerance. We have combined our efforts to achieve a wider, more detailed understanding of salt tolerance in plants mediated by ion transport, to understand present and future ways to modify and manipulate ion transport and salinity tolerance and also to find natural limits for the modifications.

Allorecognition by Leukocytes of the Adaptive Immune System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453863 Year: Pages: 107 DOI: 10.3389/978-2-88945-386-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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The term allorecognition refers to the series of mechanisms used by an individual’s immune system to distinguish its own cells and tissues from those of another individual belonging to the same species. During evolution, different cells and molecules of both innate and adaptive immune systems have been selected to recognize and respond to antigens expressed by allogeneic cells, but not autologous cells (alloantigens). This research topic focuses on allorecognition by lymphocytes of the adaptive immune system and its involvement in rejection or tolerance of allogeneic transplants. T and B cells recognizing alloantigens via specific receptors become activated and undergo proliferation and differentiation into different types of effector and memory cells. Allorecognition by lymphocytes occurs regularly during pregnancy upon trafficking of both maternal and fetal cells. In this setting, allorecognition triggers an alloresponse that is protective towards the fetus thus preventing abortion. Protective alloimmunity is mediated through cooperation between different lymphocytes and antigen presenting cells (APCs), as well as regulatory mediators and receptors. Likewise, certain transplants placed in organs and tissues called immune-privileged sites such as the eye, the central nervous system and the testis elicit protective rather than destructive adaptive immune responses. Therefore, under certain circumstances, allorecognition by regulatory lymphocytes (Tregs and Bregs) can lead to tolerance of alloantigens. In contrast, allorecognition by T cells in non-immune privileged sites and under inflammatory conditions leads to a destructive immune response. Indeed, after transplantation of most allogeneic organs and tissues, activation of pro-inflammatory T cells (TH1 and TH17), which recognize donor MHC proteins (direct pathway) or peptides derived from donor MHC and minor antigens (indirect pathway), leads to graft rejection. This inflammatory response leads to the differentiation of allospecific cytotoxic T cells as well as production of donor specific antibodies by B cells, both of which contribute to the destruction of the transplant. In this Research Topic, we describe the different pathways of allorecognition by T cells involved in allograft rejection, as well as the role of different antigen presenting cells and graft-derived microvesicles (exosomes) involved in this process. Another aspect of this Research Topic addresses the essential role of alloreactive memory T cells in allograft rejection and resistance to transplant tolerance induction in laboratory rodents, as well as non-human primates and patients. Indeed, it has become evident that laboratory mice display very few memory alloreactive T cells pre-transplantation, essentially due to the fact that they are raised in pathogen-free facilities. In contrast, primates display high frequencies of alloreactive memory T cells, either generated through prior exposure to allogeneic MHC molecules or via cross-reactivity with microbial antigens. We and others have provided ample evidence showing that this feature accounts for differences in terms of tolerance susceptibility between laboratory rodents and patients. This implies that further investigation of tolerance protocols in laboratory mice should be performed using “dirty mice” i.e., mice raised in non-sterile conditions. In summary, this Research Topic addresses key aspects of allorecognition by lymphocytes and alloantigen presentation by dendritic cells, and specifically how these processes shape our immune system and govern the rejection or tolerance of allogeneic tissues and organs.

10 Weltbürger Perspectives and Samhandling (Book chapter)

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ISBN: 9788202535025 Year: Pages: 10 DOI: 10.23865/noasp.36.ch10 Language: English
Publisher: Cappelen Damm Akademisk/NOASP (Nordic Open Access Scholarly Publishing)
Subject: Sociology --- Social Sciences
Added to DOAB on : 2019-01-15 13:34:09
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"The chapter starts with a criticism of management and control concepts&#xD;that have been rooted in economic or psychological theories and models, although&#xD;society’s complexity and the pace of change will demand a broader and deeper foundation&#xD;for the development of effective management systems in the future. Other&#xD;voices need to be put forward. Immanuel Kant (1795/1991) argued for his idea of the&#xD;Weltbürger (“world citizen”), also known as “The Cosmopolitan Ideal”. His fundamental&#xD;philosophy is that all humans are welcome, regardless of time and place, and&#xD;that all humans are world citizens, regardless of nationality and cultural belonging&#xD;(Kant, 1795/1991). All people are co-citizens, independent of nationality and cultural&#xD;affiliation, and the Weltbürger is concerned with global problems and solutions.&#xD;Another central thinker is Jacques Derrida (1930–2004), a French philosopher and&#xD;writer particularly known for the term “Deconstruction”, which is about splitting up&#xD;words and phrases to find out what they really mean, in the light of the culture and&#xD;underlying attitudes. Human comprehension requires common words and phrases&#xD;(language), and a cultural and social context, both of which have formed the basis&#xD;for conceptual analysis of the terms “hospitality” and “threshold of tolerance”. The&#xD;conclusion is that the concepts of the Weltbürger and “hospitality” have important&#xD;values in and of themselves, and are ideas that are universal and timeless, providing&#xD;an important compass for samhandling."&#xD;

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