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Molecular Immunotoxicology


Molecular Immunotoxicology


1. Aufl.

von: Emanuela Corsini, Henk Van Loveren

133,99 €

Verlag: Wiley-VCH
Format: EPUB
Veröffentl.: 06.08.2014
ISBN/EAN: 9783527676996
Sprache: englisch
Anzahl Seiten: 352

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Beschreibungen

The human immune system is constantly exposed to chemical contaminants, whether from food, water or air. Some chemicals directly elicit an immune response, while others indirectly activate or deactivate components within the immune system. Thus when tracking or predicting the effect of a chemical on the immune system, many different pathways and modes of action need to be considered. Following an introduction to the various pathways and toxicity mechanisms from a systemic perspective, the main part of this comprehensive reference surveys individual molecular mechanisms of important immunotoxicants, from PAHs to biopharmaceuticals, and from receptor-mediated toxicity to nanoparticle toxicity, using analyses based on molecular effects rather than on animal models. Taken together, the knowledge presented here provides an up-to-date overview of this hot topic that can be directly applied to the prediction and characterization of immunotoxic effects in drugs, chemicals, and environmental contaminants.
Preface THE EVOLUTION OF IMMUNOTOXICOLOGY Introduction Immune-Mediated Environmental Lung Diseases Immunotoxic Drug Reactions Autoimmunity Immunosuppression Allergic Contact Dermatitis (ACD) Summary OVERVIEW OF THE MECHANISMS UNDERLYING CHEMICAL-INDUCED IMMUNOTOXICOLOGY Introduction Mechanisms of Immunotoxicity Conclusions USE OF TOXICOGENOMICS IN IMMUNOTOXICOLOGY Introduction Toxicogenomics Bioinformatics and Data Analysis Multiple Omic Approaches in the Evaluation of Immunosuppressive Compounds Summary and Conclusions BREAKDOWN OF THE MOLECULAR PROCESSES DRIVING THE ADVERSE OUTCOME PATHWAYS (AOPs) OF SKIN AND RESPIRATORY SENSITIZATION INDUCTION IN HUMANS EXPOSED TO XENOBIOTICS AND PROTEINS Introduction The AOP for Skin Sensitization The Molecular Processes in the MOA for Sensitization Induction Summary CHEMICAL ALLERGEN-INDUCED SKIN CELL ACTIVATION Introduction Breaching in Barriers Role of the Extracellular Matrix in Skin Inflammation Cytoprotective Responses and Skin Inflammation Skin Dendritic Cells - Tolerance versus Immunity DC Activation and Migration The Role of Danger Signals Inappropriate/Compromised DC Activation T-Cell Activation and Immune Regulation Allergic Contact Dermatitis as a (Sterile) "Infection" - Implications THE ARYL HYDROCARBON RECEPTOR (AhR) AS A MEDIATOR OF ADVERSE IMMUNE REACTIONS Introduction The Arylhydrocarbon Receptor - a Sensor of Chemicals and a Link to Our Chemical Environment Immunotoxicity of TCDD, the Paradigm Ligand of AhR AhR-Deficient Animal Models to Study AhR Function in the Immune System Concluding Remarks IMMUNOTOXICOLOGICAL EFFECTS OF PHARMACEUTICALS ON SIGNAL TRANSDUCTION IN INNATE AND ADAPTIVE IMMUNITY Introduction Drug Affecting Signal Transduction in Innate Immunity Drug affecting Signal Transduction in Adaptive Immunity PROMISES AND CHALLENGES WITH IMMUNOMODULATORY BIOLOGICS Introduction Adaptive Immunity in the Control of Tumors Recent Developments in Oncology Immunotherapy - Case Examples Conclusions THE NONCLINICAL EVALUATION OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS, MOVING ON AFTER THE TEGENERO CASE The TeGenero (TGN1412) Case The EU CHMP Risk Mitigation Document MABEL versus NOAEL Approach Predictivity of Antibody Properties, Pharmacodynamics, Pharmacokinetics, and Toxicology New Developments in Biological Testing: In Vitro Approaches? Cytokine Release Assays Conclusions GLUCOCORTICOLD-INDUCED IMMUNOMODULATION Introduction Mechanism of Action GC Resistance GC Effects on the Immune System GC, Inflammation, and Immunosuppression GC and Autoimmunity Conclusions and Perspectives PARTICULATE MATTER-INDUCED IMMUNE ACTIVATION Background and Introduction The Human Evidence Do Physical or Chemical Particle Components Mediate Immune Stimulation? Particle Adjuvant Effect - The Primary and Secondary Response Particle Properties and Adjuvant Effect - Size is a Critical Factor Interactions of Particles with the Immune System Genetic Factors Mechanisms of Particle Adjuvanicity Oxidative Stress Summary and Conclusions GENOTOXIC MECHANISMS OF PAH-INDUCED IMMUNOTOXICITY Introduction General Chemical Structure of PAHs Aryl Hydrocarbon Receptor (AhR)-Mediated Immunotoxicity Pathways PAH-Induced Immunotoxicity via AhR-Independent Pathway Microsomal Epoxide Hydrolase (mEH) Genotoxic Pathways PAH-Induced Apoptosis Pathways in T Cells, B Cells, and Macrophages IMMUNOTOXIC EFFECTS OF PERFLUOROALKYLATED COMPOUNDS: MECHANISMS OF ACTION Introduction Immune Effects of PFOA and PFOS in Animal Models Immune Effects of PFOA and PFOS in Humans Mechanisms of Action Conclusions PESTICIDE-INDUCED IMMUNOTOXICITY: MOLECULAR TARGETS Introduction Summary MODE OF ACTION OF ORGANOTINS IN IMMUNE CELLS Introduction to Tributyltin Compounds Findings on Immunotoxicity of TBTs Based on Animal Studies Differential Effects of TBTs on Prenatal, Postnatal, or Adult Rats Lactational Transfer of TBT Effects of Organotin Compounds on the Immune Function of Aquatic Organisms Modes of Action of TBTO as Assessed by Cytological and Biochemical Assays Toxicogenomics Studies on the Modes of Action of TBTs Summary Index
Emanuela Corsini is associate professor in toxicology at the School of Pharmacy at the University of Milan (Italy), where she heads the Laboratory of Immunotoxicology and Immunopharmacology. She obtained her PhD in Food and Environmental Toxicology in 1993 at Milan and subsequently spent a post-doc period at NIEHS, Research Triangle Park (USA). Professor Corsini is active in numerous scientific and professional organizations, and serves on several journal editorial boards. From 2005 to 2011 she was the Chair of the Immunotoxicology and Chemical Specialty Section at EUROTOX, and since 2010 she is one of the Directors of the IUTOX Executive Committee.Henk van Loveren got his PhD at Utrecht University (The Netherlands). He spent a post-doc period at Yale University, New Haven (USA), and subsequently joined the Netherlands National Institute of Public Health and the Environment at Bilthoven, where he directs the immunotoxicology program. He is also professor of immunotoxicology at Maastricht University. From 2000 to 2003 he was the chair of the Immunotoxicology and Chemical Specialty Section at EUROTOX. He serves as the director of the WHO/IPCS Collaborative Centre of Immunotoxicology and Allergic Hypersensitivity, has served at the Nutrition, Dietetic Products and Allergies Panel of EFSA, and is currently member of the CONTAM Panel of EFSA. For his activities in the field of Immunotoxicology he got the Vos Career Achievement Award of the SOT in 2008, and the Merit Award from EUROTOX in 2010.
The human immune system is constantly exposed to chemical contaminants, whether from food, water or air. Some chemicals directly elicit an immune response, while others indirectly activate or deactivate components within the immune system. Thus when tracking or predicting the effect of a chemical on the immune system, many different pathways and modes of action need to be considered. Following an introduction to the various pathways and toxicity mechanisms from a systemic perspective, the main part of this comprehensive reference surveys individual molecular mechanisms of important immunotoxicants, from PAHs to biopharmaceuticals, and from receptor-mediated toxicity to nanoparticle toxicity, using analyses based on molecular effects rather than on animal models. Taken together, the knowledge presented here provides an up-to-date overview of this hot topic that can be directly applied to the prediction and characterization of immunotoxic effects in drugs, chemicals, and environmental contaminants.

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