Experimental and Mathematical Analysis of Regulatory Networks in T-helper Lymphocytes PDF Download
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Author: Edda G. Schulz
Publisher: Logos Verlag Berlin GmbH
ISBN: 3832524983
Category : Mathematics
Languages : en
Pages : 173
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Book Description
In this book, an interdisciplinary approach combining dynamic quantitative measurements with mathematical modelling is used to solve two different problems in molecular immunology. In the first part, structure and function of the gene-regulatory network that controls differentiation of type I T-helper (Th1) cells is investigated. By determining the network structure through an iterative process of modelling and experiments, the author shows that Th1 differentiation proceeds in two steps: In the early effector phase, the Th1 master transcription factor T-bet is controlled by an interferon-? dependent positive feedback loop, while in the later phase a second IL-12 dependent feedback maintains T-bet expression. The antigen signal acts as a switch between the two pathways. Moreover, it is shown that only T-bet expression in the late phase is predictive of the success of the differentiation process. Since T-bet expression in the late phase requires IL-12 stimulation, this work uncovers the molecular mechanisms behind the unique role of IL-12 in Th1 differentiation. In the second part, regulation of the transcription factor NFAT that mediates antigenic stimulation in T-cells is investigated. NFAT is activated by nuclear import upon dephosphorylation of multiple residues. Based on simultaneous measurements of NFAT subcellular localization and phosphorylation, a quantitative mathematical model of the NFAT regulatory network is developed and the underlying design principles are analyzed. In summary, the study exemplifies the necessity of a dynamic analysis at the systems level to understand complex biological processes.
Author: Edda G. Schulz
Publisher: Logos Verlag Berlin GmbH
ISBN: 3832524983
Category : Mathematics
Languages : en
Pages : 173
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Book Description
In this book, an interdisciplinary approach combining dynamic quantitative measurements with mathematical modelling is used to solve two different problems in molecular immunology. In the first part, structure and function of the gene-regulatory network that controls differentiation of type I T-helper (Th1) cells is investigated. By determining the network structure through an iterative process of modelling and experiments, the author shows that Th1 differentiation proceeds in two steps: In the early effector phase, the Th1 master transcription factor T-bet is controlled by an interferon-? dependent positive feedback loop, while in the later phase a second IL-12 dependent feedback maintains T-bet expression. The antigen signal acts as a switch between the two pathways. Moreover, it is shown that only T-bet expression in the late phase is predictive of the success of the differentiation process. Since T-bet expression in the late phase requires IL-12 stimulation, this work uncovers the molecular mechanisms behind the unique role of IL-12 in Th1 differentiation. In the second part, regulation of the transcription factor NFAT that mediates antigenic stimulation in T-cells is investigated. NFAT is activated by nuclear import upon dephosphorylation of multiple residues. Based on simultaneous measurements of NFAT subcellular localization and phosphorylation, a quantitative mathematical model of the NFAT regulatory network is developed and the underlying design principles are analyzed. In summary, the study exemplifies the necessity of a dynamic analysis at the systems level to understand complex biological processes.
Author: Geoffrey W. Hoffman
Publisher: CRC Press
ISBN: 1000697053
Category : Health & Fitness
Languages : en
Pages : 334
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Book Description
First published in 1986: Paradoxes play a key role in the advancement of science. They are associated with excitement, and with the knowledge that we must be looking at something the wrong way. This book discusses in detail Paradoxes in Immunology.
Author: Dorothea Busse
Publisher: Logos Verlag Berlin GmbH
ISBN: 3832526935
Category : Science
Languages : en
Pages : 114
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Book Description
This book adds to a intensively investigated question of immunological research. How do regulatory T cells mediate their function to ensure tolerance against self-antigen? The author analyzes the interaction via the cytokine interleukin 2 between T helper cells, which mediate immune responses, and regulatory T cells. Since both cell types depend on interleukin 2 to mediate their functions, competition for interleukin 2 is likely. A mathematical model is developed to describe the interaction. This model focuses on the interleukin 2 receptor dynamics on helper and regulatory T cells and the extracellular interleukin 2 diffusion. The interleukin 2 receptor dynamics is governed mainly by an autocrine positive feedback loop on both cell types. However, its differential regulation results in a switch-like up-regulation of the receptors on T helper cells and a gradual adaptation of the receptor levels to extracellular interleukin 2 supply on regulatory T cells. This difference enables regulatory T cells to efficiently compete for interleukin 2 and deprive T helper cells of their growth factor. Cell culture experiments verify these findings. It can be shown that the antigen stimulus and the intercellular distance are relevant control parameters for competition. Other mechanisms are described for suppression of T helper cell action by regulatory T cells; competition for interleukin 2 may act in concert with them.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1064
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Book Description
Author: Ramit Mehr
Publisher: Frontiers Media SA
ISBN: 2889195015
Category : Immunologic diseases. Allergy
Languages : en
Pages : 402
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Book Description
The rapid development of new methods for immunological data collection – from multicolor flow cytometry, through single-cell imaging, to deep sequencing – presents us now, for the first time, with the ability to analyze and compare large amounts of immunological data in health, aging and disease. The exponential growth of these datasets, however, challenges the theoretical immunology community to develop methods for data organization and analysis. Furthermore, the need to test hypotheses regarding immune function, and generate predictions regarding the outcomes of medical interventions, necessitates the development of mathematical and computational models covering processes on multiple scales, from the genetic and molecular to the cellular and system scales. The last few decades have seen the development of methods for presentation and analysis of clonal repertoires (those of T and B lymphocytes) and phenotypic (surface-marker based) repertoires of all lymphocyte types, and for modeling the intricate network of molecular and cellular interactions within the immune systems. This e-Book, which has first appeared as a ‘Frontiers in Immunology’ research topic, provides a comprehensive, online, open access snapshot of the current state of the art on immune system modeling and analysis.
Author: Ana Karina de Oliveira
Publisher: Frontiers Media SA
ISBN: 283250132X
Category : Science
Languages : en
Pages : 309
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Book Description
Author:
Publisher:
ISBN:
Category : Power resources
Languages : en
Pages : 780
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Book Description
Author: Henri Atlan
Publisher: Springer Science & Business Media
ISBN: 3642839355
Category : Medical
Languages : en
Pages : 123
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Book Description
For a long time, immunology has been dominated by the idea of a simple linear cause-effect relationship between the exposure to an antigen and the production of specific antibodies against that antigen. Clonal selection was the name of the theory based on this idea and it has provided the main concepts to account for the known features of the immune response. More recently, immunologists have discovered a wealth of new facts, in the form of different regulatory cells (helpers, suppressors, antigen presenting cells), genetic determinations of immune responses such as those involved in graft re jections, different molecular structures responsible for intercellular interactions such as interleukins, cytokins, idiotype-antiidiotype recognition and others. While furthering our understanding of the local interactions (molecular and cellular) in volved in the immune response, these discoveries have led to a questioning of the simplicities of the classical clonal selection theory. It is clear today that every single immune response is a cooperative phenomenon involving several different molecular and cellular interactions taking place in a coupled manner. In addition, cross reactivity to different antigens has shown that responses of the whole im mune system to different antigens are not completely isolated from one another and that the history of encounters with different antigens plays a crucial role in the maturation of the whole system. Thus, problems of complexity, generation of di versity and self-organization have entered the field of immunology.
Author: Antonia Vlahou
Publisher: John Wiley & Sons
ISBN: 1119183979
Category : Science
Languages : en
Pages : 388
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Book Description
Introduces readers to the state of the art of omics platforms and all aspects of omics approaches for clinical applications This book presents different high throughput omics platforms used to analyze tissue, plasma, and urine. The reader is introduced to state of the art analytical approaches (sample preparation and instrumentation) related to proteomics, peptidomics, transcriptomics, and metabolomics. In addition, the book highlights innovative approaches using bioinformatics, urine miRNAs, and MALDI tissue imaging in the context of clinical applications. Particular emphasis is put on integration of data generated from these different platforms in order to uncover the molecular landscape of diseases. The relevance of each approach to the clinical setting is explained and future applications for patient monitoring or treatment are discussed. Integration of omics Approaches and Systems Biology for Clinical Applications presents an overview of state of the art omics techniques. These methods are employed in order to obtain the comprehensive molecular profile of biological specimens. In addition, computational tools are used for organizing and integrating these multi-source data towards developing molecular models that reflect the pathophysiology of diseases. Investigation of chronic kidney disease (CKD) and bladder cancer are used as test cases. These represent multi-factorial, highly heterogeneous diseases, and are among the most significant health issues in developed countries with a rapidly aging population. The book presents novel insights on CKD and bladder cancer obtained by omics data integration as an example of the application of systems biology in the clinical setting. Describes a range of state of the art omics analytical platforms Covers all aspects of the systems biology approach—from sample preparation to data integration and bioinformatics analysis Contains specific examples of omics methods applied in the investigation of human diseases (Chronic Kidney Disease, Bladder Cancer) Integration of omics Approaches and Systems Biology for Clinical Applications will appeal to a wide spectrum of scientists including biologists, biotechnologists, biochemists, biophysicists, and bioinformaticians working on the different molecular platforms. It is also an excellent text for students interested in these fields.
Author:
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ISBN:
Category : Power resources
Languages : en
Pages : 786
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Book Description
Semiannual, with semiannual and annual indexes. References to all scientific and technical literature coming from DOE, its laboratories, energy centers, and contractors. Includes all works deriving from DOE, other related government-sponsored information, and foreign nonnuclear information. Arranged under 39 categories, e.g., Biomedical sciences, basic studies; Biomedical sciences, applied studies; Health and safety; and Fusion energy. Entry gives bibliographical information and abstract. Corporate, author, subject, report number indexes.
