Basic Immunology: Functions and Disorders of the Immune System, 6e: SAE-E-book

Modern healthcare faces a significant challenge, namely that 25-70% of patients with common diseases do not benefit from standard treatments despite the availability of over 13,000 drugs registered in DrugBank. This discrepancy is likely due to these diseases' complex and heterogeneous molecular nature rather than a lack of therapeutic options. Emerging technologies have revealed the immense molecular complexity underlying common diseases. For instance, singlecell RNA sequencing (scRNA-seq) has demonstrated altered gene interactions in and across multiple cell types in numerous tissues. Furthermore, these technologies have revealed vast molecular differences between patients with the same diagnosis. There is a wide gap between this complexity and the current diagnostic and therapeutic approaches. Aim: To bring personalized medicine one step closer to the clinic; this thesis focuses on developing digital disease models that can capture the molecular biological complexity of disease in individual patients. We aim to harness these disease models to identify optimal treatments for each individual patient. Paper I: We started by exploring the usefulness of OMIC-based approaches for diagnostic and therapeutic predictions. Utilizing a single-cell RNA-sequenced mouse model of antigen-induced arthritis, we aimed to prioritize cell types and therapeutic targets. Initial pathway enrichment analyses did not yield relevant prioritization, prompting an investigation into network-based approaches. Multi-cellular disease models (MCDMs) for AIA and human rheumatoid arthritis were constructed, incorporating predicted cell type interactions. Centrality analysis indicated that these interactions could quantify a cell type’s relative importance in disease pathogenesis. We hypothesized that transcriptomic alterations in central cell types might reflect the MCDM, serving as potential diagnostic markers. An analysis of CD4+ T cells from patients with 13 different inflammatory diseases and healthy controls demonstrated that these profiles could discriminate between healthy and diseased states and among diseases. Furthermore, a network-based approach identified drugs targeting disease- associated changes common to multiple inflammatory diseases. Notably, one of these drugs, bezafibrate, successfully dampened inflammation in the AIA mouse model. Paper II: Building on the insights from Paper I, we investigated multicellular network models (MNMs) with time as an additional dimension. Using seasonal allergic rhinitis (SAR) as a disease model, we analyzed time-series scRNAseq data to construct MNMs of inflammatory diseases. We identified thousands of disease-associated expression changes across multiple cell types, varying at different disease stages. Notably, upstream regulators (URs) of these changes were also stage-dependent and multidirectional. To prioritize URs for drug discovery, we focused on those causing significant expression changes in multiple cell types across all time points. This strategy was validated through similar analyses of atopic dermatitis, ulcerative colitis, and Crohn’s disease, confirming that ranked URs aligned with the efficacy of existing drugs targeting the URs in the respective diseases. Furthermore, experimental validation included targeting the top-ranked regulatory gene in SAR, which was more effective than previously discovered IL4 inhibition. Paper III: While Paper I established the use of transcriptomic data for therapeutic predictions, it focused on overlapping disease-related changes across multiple inflammatory diseases and considered transcriptomic changes in only one cell type. Paper II indicated a potential benefit in UR prioritization in numerous cell types. However, it yielded heterogeneous results and was limited by the fact that few drugs directly target URs. Neither of these approaches was feasible for individualized drug predictions. Drawing on previous insights by us and others, we next aimed to develop digital disease models for individual patients, termed digital twins, with the capability for drug efficacy screening. We proposed scDrugPrio, a strategy utilizing single-cell scRNA-sequencing-based multicellular disease models incorporating key biological and pharmacological properties, such as varying gene expression levels, varying gene interactions within and between cell types, and drug effect. scDrugPrio was constructed based on a mouse model of arthritis and validated by improved precision/recall for known drugs and in vitro studies of predicted drugs that were FDA approved for other diseases and had not yet been tried in rheumatoid arthritis or mouse arthritis. For validation, scDrugPrio was applied to human multiple sclerosis as well as Crohn’s disease data that included tissue samples from healthy and sick tissue of all patients; scDrugPrio was able to identify relevant treatments for individual patients and could distinguish anti-TNF responders from non-responders. Conclusion: This thesis demonstrates a framework for constructing digital disease models for personalized therapeutic predictions that might hold potential for better clinical treatment decisions. By leveraging advanced genome-wide analyses and network-based approaches, we may enhance the precision and efficacy of treatments for immune-mediated inflammatory diseases, bringing personalized medicine closer to clinical reality.

Meticulously reviewed and updated for today's medical students, Basic Immunology, 6th Edition, is a concise text expertly written by the same distinguished author team as the best-selling, comprehensive text, Cellular and Molecular Immunology. This focused, easy-to-understand volume uses full-color illustrations and clinical images, useful tables, and practical features such as Summary Point boxes, end-of-chapter review questions, glossary terms, and clinical cases—all designed to help students master this complex topic in the most efficient, effective manner possible. - Emphasizes clinical aspects of immunology, including disease pathogenesis, the development of novel therapies based on basic science, and an appendix of clinical cases for real-world application. - Provides top-notch instruction from experienced teachers, course directors, and lecturers led by well-known editor and author Dr. Abul Abbas. - Features a highly readable writing style and practical organization, now with fully revised content and updated images to reflect recent important advances in today's understanding of the immune system. - Presents information in a format and style that maximizes usefulness to students and teachers studying medicine, allied health fields, and biology. - Contains numerous features designed to help students understand key immunologic concepts: high-quality illustrations, practical tables, chapter outlines, bolded key points, and focus questions in every chapter for self-assessment and review. - Evolve Instructor site with a downloadable image bank is available to instructors through their Elsevier sales rep or via request at: https://evolve.elsevier.com

In this updated edition of Basic Immunology, the authors continue to deliver a clear, modern introduction to immunology, making this the obvious choice for today's busy students. Their experience as teachers, course directors, and lecturers helps them to distill the core information required to understand this complex field. Through the use of high-quality illustrations, relevant clinical cases, and concise, focused text, it's a perfectly accessible introduction to the workings of the human immune system, with an emphasis on clinical relevance. - Concise, clinically focused content is logically organized by mechanism for efficient mastery of the material. - Features an appendix of clinical cases and CD molecules. - Includes numerous full-color illustrations, useful tables, and chapter outlines. - Focus questions within each chapter are ideal for self-assessment and review. - Key points bolded throughout the text make it easy to locate important information. - Presents information in a format and style that maximizes usefulness to students and teachers studying medicine, allied health fields, and biology. - Fully updated content equips you with the latest relevant advances in immunology. - Revised and updated artwork enhances your visual learning of important principles and reduces the excessive factual details found in larger textbooks. - Twelve brand-new animations available on Student Consult help further explain complex concepts. - Student Consult eBook version included with purchase. This enhanced eBook experience gives you access to the text, figures, images, glossary of immunology terms, self-assessment questions, and references on a variety of devices.

Understand all the essential concepts in immunology with Basic Immunology: Functions and Disorders of the Immune System! This concise, focused text provides you with an up-to-date, accessible introduction to the workings of the human immune system. Efficiently master the immunology information you need through clinically focused content, logically organized by mechanism. Apply what you've learned to real-world situations by referencing the appendix of clinical cases. Enhance your learning with the help of numerous full-color illustrations and useful tables, as well as summary boxes, review questions, and a glossary of immunology terms. Study immunology anywhere! Online access to www.StudentConsult.com opens the door to an enhanced e-book and ancillary components! Visualize complex immunology concepts with a completely updated art program. Test your knowledge. New PowerPoint Review slides added to www.StudentConsult.com are ideal for study sessions.

This updated 3rd edition of Basic Immunology provides a readable and concise introduction to the workings of the human immune system, with emphasis on clinical relevance. The format makes learning easy with short, easy-to-read chapters, color tables, key point summaries, and review questions in every chapter. You’ll get the latest coverage on regulatory T cells, biology of the Th17 subset of CD4+ T cells, and more. The full-color artwork, comprehensive glossary, and clinical cases are just some of the features that reinforce and test your understanding of how the immune system functions. Covers the most up-to-date immunology information including regulatory T cells, and biology of the Th17 subset of CD4+ T cells to keep you completely current. Relates basic science to clinical disorders through clinical cases for better application in a real-world setting. Provides a full Glossary to keep you on the cutting edge of immunologic terminology. Includes appendices summarizing the features of CD Molecules, a handy Glossary, and Clinical Cases that test your understanding of how the immune system functions in health and disease. Presents beautiful full-color artwork for enhanced visual learning.