Download or read book Toll Like Receptor Activation in Immunity vs Tolerance written by Christophe M. Filippi and published by Frontiers Media SA. This book was released on 2016-01-12 with total page 77 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Toll Like Receptor Activation in Immunity Vs Tolerance written by and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Toll Like Receptors TLRs and Innate Immunity written by Stefan Bauer and published by Springer Science & Business Media. This book was released on 2007-12-11 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.
Download or read book Toll like Receptors in Health and Disease written by Vijay Kumar and published by Springer Nature. This book was released on 2022-06-06 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: The current book is focussed on the Toll-like receptors (TLRs), which are the first pattern recognition receptors (PRRs) discovered in humans. For example, TLR4 was first recognized in humans in 1997 as a PRR recognizing the Gram-negative bacterial lipopolysaccharide (LPS). This discovery revolutionized the field of innate immunity and filled the long-standing gap in the pathogen recognition by the immune system. Now, it is well established that humans have 10 (TLR1-TLR10) and mice have 12 (TLR1-TLR13) functional TLRs, excluding TLR10 that is present as a defective pseudogene. TLRs are present as both membrane-bound extracellular (TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10) and intracellular (TLR3, TLR7, TLR8, and TLR9) PRRs in humans, which identify different pathogen or microbe-associated molecular patterns (PAMPs or MAMPs) and death or damage-associated molecular patterns (DAMPs) released by the host cells. A lot of development in the TLR biology has occurred in last 24 years since there first discovery in humans. The book is intended to describe their role in the host defence, human reproduction, non-infectious sterile inflammatory conditions, including brain immunity and cerebrovascular diseases, signaling mechanisms, adaptive immunity, and their targeting for drug development.
Download or read book Toll and Toll Like Receptors written by Tina Rich and published by Springer Science & Business Media. This book was released on 2007-03-11 with total page 227 pages. Available in PDF, EPUB and Kindle. Book excerpt: Toll Receptors and the Renaissance of Innate Immunity Elizabeth H. Bassett and Tina Rich Overview n the last few pages of Immunology: The Science of Self-Nonself Discrimination Jan Klein ponders on what he would study if he were to start over in the lab. ^ Dismissing the I antibody, MHC, the T-cell and parasitology, he considers instead the phylogeny of immune reactions, particularly in ancient phyla. As for a favored cell he chooses the macrophage. Describ ing it as a ^^MddchenfUr alles," (all purpose kitchen maid) Klein believed that this immunocyte still had secrets to reveal. Toll-Like Receptor (TLR) biology would prove to be one of these secrets. Analyses of the evolution of these receptors (Tolls and TLRs) have also helped us to rethink immune system phylogeny. In the first part of this chapter the history of the discovery of Toll and TLR biology is described. The evolution of the TLR genes and theories of immune function are covered in later sections. The remainder of this book presents work from nine groups active in the field. In the first chapter, "The Function of Toll-Like Receptors", Zlatko Dembic sets the stage by introducing us to many of the components of the immune system and their relationships vis a vis Toll receptors. Zlatko finishes his chapter with a discussion about current immune system models and contributes his own 'integrity model'. Work from the laboratory of Nicholas Gay follows this in "Structures and Motifs Involved in Toll Signaling".
Download or read book Immunology of Fungal Infections written by Gordon D. Brown and published by Springer Science & Business Media. This book was released on 2007-05-10 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text covers all aspects of the immunology of fungal infection. Beyond the basics, coverage includes recent developments in innate and adaptive immunological mechanisms involved in the host response to fungal infection. The volume’s topical sections provide an immunological perspective on the cells, soluble factors and receptors involved in recognising and combating fungal infections. Discussion includes descriptions of immunity to specific pathogens, immune-escape mechanisms used by fungi, and therapeutic strategies.
Download or read book The nature of activatory and tolerogenic dendritic cell derived signal 2 written by Francesca Granucci and published by Frontiers E-books. This book was released on 2014-07-08 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most interesting issues in immunology is how the innate and adaptive branches of the immune system cooperate in vertebrate organisms to respond and destroy invading microorganisms without destroying self-tissues. More than 20 years ago, Charles Janeway proposed the innate immune recognition theory [1]. He hypothesized the existence of innate receptors (Pattern recognition receptors, PRRs) that, by recognizing molecular structures associated to pathogens (PAMPs) and being expressed by antigen presenting cells (APCs) and epithelial cells, could alert the immune system to the presence of a pathogen, making it possible to mount an immediate inflammatory response. Moreover, by transducing the alert signal in professional APCs and inducing the expression of costimulatory molecules, these receptors could control the activation of lymphocytes bearing clonal antigen-specific receptors, thereby promoting appropriate adaptive immune responses. Since adaptive immunity can be activated also following sterile inflammatory conditions, it was subsequently proposed by Polly Matzinger that the innate immune system could be also activated by endogenous danger signals, generically called danger associated molecular patterns (DAMPs)[2]. The first prediction has been amply confirmed by the discovery of Toll-like receptors [3; 4; 5] and cytoplasmic PRRs such as RIG-like receptors [6]. Other PRR families such as the NOD-like receptors and C-type lectins exert immunogenic or tolerogenic signals [7; 8; 9] and may recognize not strictly pathogens but also endogenous danger signals that may lead to inflammasome activation [10; 11] . Dendritic cells (DCs) have been identified as the cells of the innate immune system that, by sensing PAMPs or DAMPs transduce signals to the nucleus. This leads to a transcriptional reprogramming of DCs with the consequent expression of three signals, namely signal 1 (MHC+peptide), signal 2 (surface costimulatory molecules) and signal 3 (cytokines) necessary for the priming of antigen-specific naïve T cell responses (signal 1 and 2) and T cell polarization (signal 3). The reason why DCs are superior with respect to other professional APCs in naïve T cell activation has not been unequivocally defined but in vivo may mainly result from their migration capacity to secondary lymphoid organs. It has not been established whether DCs can provide a special “signal 2” or simply very high levels, compared with other APCs, of commonly expressed signals 1 and 2, so that a naïve T cell could reach the threshold of activation. A second aspect of DC biology needs also to be taken into account. Concerning the question of how self-tissues are not destroyed following the initiation of adaptive immune responses, different mechanisms of central and peripheral auto-reactive T cell tolerization have been proposed [12]. In particular, it has been defined that high affinity T cells are deleted in the thymus, while low affinity auto-reactive T cells or T cells specific for tissue-sequestered antigens that do not have access to the thymus are controlled in the periphery. In a simplified vision of how peripheral T cell tolerance could be induced and maintained, it was thought that, in resting conditions, immature DCs, expressing low levels of signal 1 and low or no levels of signal 2, were able to induce T cell unresponsiveness. Nevertheless, it is now clear that a fundamental contribution to the peripheral tolerance is due to the conversion of naïve T cells into peripheral regulatory T cells (pTreg cells) and it is also clear that DCs need to receive a specific conditioning to become able to induce pTreg cell differentiation. Even more intriguing is that also DCs activated through PRRs, with particular Toll like receptor (TLR) agonists, are capable of generating pTreg cell conversion if these agonists induce the production of the appropriate cytokines.
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Evolution of the Immune System written by Davide Malagoli and published by Academic Press. This book was released on 2016-05-24 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Evolution of the Immune System: Conservation and Diversification is the first book of its kind that prompts a new perspective when describing and considering the evolution of the immune system. Its unique approach summarizes, updates, and provides new insights on the different immune receptors, soluble factors, and immune cell effectors. Helps the reader gain a modern idea of the evolution of the immune systems in pluricellular organisms Provides a complete overview of the most studied and hot topics in comparative and evolutionary immunology Reflects the organisation of the immune system (cell-based, humoral [innate], humoral [adaptive]) without introducing further and misleading levels of organization Brings concepts and ideas on the evolution of the immune system to a wide readership
Download or read book Nutritional Pathophysiology of Obesity and its Comorbidities written by Susan Ettinger and published by Academic Press. This book was released on 2016-09-01 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nutritional Pathophysiology of Obesity and Its Comorbidities: A Case-Study Approach challenges students and practitioners to understand the role of nutrients within the pathophysiology and development of disease, specifically those diseases which develop as a result of obesity. Through a case-based approach, the author presents complex clinical scenarios that require multiple treatment strategies, including targeted diet modification as an adjuvant to medical therapy. The book is divided into 9 modules and 5 appendices each of which covers aspects of obesity and its comorbidities. Within each module, a case is detailed with relevant history, laboratory and physical data, and follow-up information. Each case is followed by a resource section which delineates current understanding of the pathophysiology of the condition, as well as the actions of nutrients and food components shown to modify these processes. A "further readings" section cites current supporting clinical and basic literature as well as published guidelines. Explores how obesity is a key player in the pathophysiology of many diseases, including diabetes mellitus, chronic renal failure, hypertension, and atherosclerosis Integrates current understandings of the molecular mechanisms of nutrient action on the processes of disease development and treatment Presents students and early practitioners with complex clinical scenarios through a practical case-based approach
Download or read book Toll like Receptor Tolerance in Dendritic Cells During Hepatitis C and HIV Infections written by Nicole L. Yonkers and published by . This book was released on 2011 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt: Host anti-viral immune responses are thought to play a critical role in mediating the spontaneous clearance of Hepatitis C infection and slow progression of HIV disease. However, in hosts with chronic Hepatitis C infection or progressive HIV disease, anti-viral responses are ineffective at clearing virus and immunopathogenesis contributes to disease progression. The work presented in this thesis evaluates immune cell phenotype and function during chronic Hepatitis C and HIV infections. Our studies focused on dendritic cells, which provide a bridge between the innate and adaptive immune response. We evaluated dendritic cell phenotype, responsiveness to TLR stimulation, and capacity to activate NK cells and naïve CD4 T cells. In addition, we evaluated HCV infected host CD4 T cell phenotype and naïve CD4 T cell activation capacity in response to TCR activating signals. Our results indicate reduced numbers of MDC likely contribute to impaired NK cell activation in the setting of HIV infection. In addition, we observed selective defects in MDC response to TLR stimulation and MDC dependent naïve CD4 T cell activation in HIV infected subjects. Finally, our evaluation of CD4 T cells in Hepatitis C infected subjects indicated that naïve CD4 T cells were reduced in number, exhibited an increased activation state, and had reduced response to TCR stimulation. Taken together the results discussed in this thesis suggest alterations in number, phenotype, and function of dendritic cells and naïve CD4 T cells exist during chronic HCV and HIV infections. We propose a model in which chronic immune activation induces selective TLR tolerance in dendritic cells during chronic HCV and HIV infections. The tolerant state of the dendritic cells likely alters DC-NK cell and DC-naïve CD4 T cell interactions, which disrupts immune cell homoeostasis and proper immune cell activation, and in essence collapses the bridge between innate and adaptive immunity.HCV and HIV infections. We propose a model in which chronic immune activation induces selective TLR tolerance in dendritic cells during chronic HCV and HIV infections. The tolerant state of the dendritic cells likely alters DC-NK cell and DC-naïve CD4 T cell interactions, which disrupts immune cell homoeostasis and proper immune cell activation, and in essence collapses the bridge between innate and adaptive immunity.
Download or read book Immunology of Pregnancy written by Gil Mor and published by Springer Science & Business Media. This book was released on 2007-12-27 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers in detail contemporary hypotheses and studies related to the immunology of implantation and provides a practical approach for the application of basic reproductive immunology research to pregnancy complications such as preeclampsia, pre-term labor and IUGR. Provides complete and up to date review of current knowledge of the role of the immune system during pregnancy and the interactions between the placenta and the maternal immune system.
Download or read book Regulation of T Cell Tolerance by Antigen coupled Splenocyte Injection written by Todd Norman Eagar and published by . This book was released on 2002 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: CD4+ T cells play a critical role in directing immune responses. T cells have the ability to recognize and respond to potentially all combinations of peptide antigens presented in MHC class II. This power allows for not only the clearance of infectious agents but also for the establishment of debilitating autoimmune conditions. Two processes known as central and peripheral tolerance limit the activity of autoimmune T cells but do not eliminate autoimmunity. Therefore, therapeutic intervention may be used to induce or restore a state of tolerance. The injection of antigen-coupled splenocytes (Ag-SP) is an effective method of inducing peripheral T cell tolerance and treating autoimmune conditions such as experimental autoimmune encephalomyelitis (EAE). The driving hypothesis of this research is that tolerance induced with Ag-SP is the result of anergy induction. Tolerance and anergy were examined in the context of B7, CTLA-4 and activation of the innate immune system. The injection of Ag-SP leads to a sharp reduction in T cell effector responses despite a rapid induction of T cell activation and proliferation. This initial "activation" resulted in an increase in antigen-specific T cells, which argues against deletion as the mechanism of tolerance induction in this scenario. Although increasing the presence of B7 on the fixed splenocytes prevents the induction of T cell unresponsiveness as measured by DTH, B7 was not required for the induction of tolerance. In vivo upregulation of B7 via toll-like receptor ligands such as LPS reversed T cell tolerance as measured by DTH and clinical disease (EAE). CTLA-4 was required for the maintenance of tolerance. Subsequent data demonstrated that CTLA-4 inhibits the activity of tolerized T cells at the level of cell-cycle entry and their ability to carry out effector functions. This suggests a larger role for CTLA-4 activity wherein CTLA-4 regulates the threshold of T cell activation making it more difficult to achieve proliferation and production of cytokines.
Download or read book Oxford Textbook of Rheumatology written by Philip Conaghan and published by Oxford University Press. This book was released on 2013-10 with total page 1553 pages. Available in PDF, EPUB and Kindle. Book excerpt: A strong clinical emphasis is present throughout this volume from the first section of commonly presenting problems through to the section addressing problems shared with a range of other clinical sub-specialties.
Download or read book Endotoxin in Health and Disease written by Helmut Brade and published by CRC Press. This book was released on 2020-10-28 with total page 968 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offering a basis for further research into the interactions of hosts and pathogens, this work gathers up-to-date findings, and details basic structures, functions and immunology. It provides descriptions of a variety of experimental endotoxin neutralizing agents, as well as a guide to clinical research initiatives and the latest treatments.
Download or read book Protein Kinase mediated Decisions Between Life and Death written by Ayse Basak Engin and published by Springer Nature. This book was released on 2021-02-04 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein phosphorylation via protein kinases is an inevitable process that alters physiological and pathological functions of the cells. Thus, protein kinases play key roles in the regulation of cell life or death decisions. Protein kinases are frequently a driving factor in a variety of human diseases including aging and cellular senescence, immune system and endothelial dysfunctions, cancers, insulin resistance, cholestasis and neurodegenerative diseases, as well as bacterial resistance in persistent infections. Recent developments in quantitative proteomics provide important opinions on kinase inhibitor selectivity and their modes of action in the biological context. Protein Kinase-mediated Decisions Between Life and Death aims to have the reader catch insights about up-to-date opinions on “Protein Kinases” related pathways that threaten human health and life. As “Protein Kinases” are related to many health problems, clinicians, basic science researchers and students need this information. Chapter “Signal Transduction in Immune Cells and Protein Kinases” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Download or read book Thyroid Autoimmunity written by A. Pinchera and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 579 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 1956, three groups independently reported evidence that some thyroid disease appearing spontaneously in humans or experimentally induced in animals are related to autoimmune processes. The interval between these landmark discoveries and the present has witnessed a remarkable and continuing growth of both knowledge and concepts concerning the mechanisms of immune regulation, the pathogenesis of autoimmune thyroid diseases, and their clinical and laboratory manifestations. More importantly knowledge of thyroid autoimmunity has, in many respects, comprised the vanguard of an ever increasing appreciation and understanding of autoimmune diseases in general. On November 24-26 1986, an International Symposium on Thyroid Autoimmunity was held in Pisa. Its purpose was to commemorate the birth of thyroid autoimmunity as a scientific discipline, to summarize current knowledge and concepts in this area, and where possible, to anticipate areas of opportunity for the future - hence the theme of the Symposium, Memories and Perspectives. To open the meeting, the Magnifico Rettore (Chancellor) of the University of Pisa granted special Awards to Dr. Deborah Doniach, Dr. Ivan Roitt, and Dr. Noel R. Rose, who published the first fundamental studies in the field of thyroid autoimmunity, and to Dr. Duncan G. Adams, whose discovery of the long-acting thyroid stimulator (LATS) opened the door to our current understanding of the pathogenesis of Graves' disease. During the meeting thirty plenary lectures were presented.
