Mathematical Immunology Of Virus Infections

This monograph concisely but thoroughly introduces the reader to the field of mathematical immunology. The book covers first basic principles of formulating a mathematical model, and an outline on data-driven parameter estimation and model selection. The authors then introduce the modeling of experimental and human infections and provide the reader with helpful exercises. The target audience primarily comprises researchers and graduate students in the field of mathematical biology who wish to be concisely introduced into mathematical immunology.

This book reviews how mathematical and computational approaches can be useful to help us understand how killer T-cell responses work to fight viral infections. It also demonstrates, in a writing style that exemplifies the point, that such mathematical and computational approaches are most valuable when coupled with experimental work through interdisciplinary collaborations. Designed to be useful to immunoligists and viroligists without extensive computational background, the book covers a broad variety of topics, including both basic immunological questions and the application of these insights to the understanding and treatment of pathogenic human diseases.

This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature

This text describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals insights into the dynamics of viral & other infections.

Beginning his work on the monograph to be published in English, this author tried to present more or less general notions of the possibilities of mathematics in the new and rapidly developing science of infectious immunology, describing the processes of an organism's defence against antigen invasions. The results presented in this monograph are based on the construc tion and application of closed models of immune response to infections which makes it possible to approach problems of optimizing the treat ment of chronic and hypertoxic forms of diseases. The author, being a mathematician, had creative long-Iasting con tacts with immunologists, geneticist, biologists, and clinicians. As far back as 1976 it resulted in the organization of a special seminar in the Computing Center of Siberian Branch of the USSR Academy of Sci ences on mathematical models in immunology. The seminar attracted the attention of a wide circle of leading specialists in various fields of science. All these made it possible to approach, from a more or less united stand point, the construction of models of immune response, the mathematical description of the models, and interpretation of results.

The immune system provides the host organism with defense mechanisms against invading pathogens and tumor development and it plays an active role in tissue and organ regeneration. Deviations from the normal physiological functioning of the immune system can lead to the development of diseases with various pathologies including autoimmune diseases and cancer. Modern research in immunology is characterized by an unprecedented level of detail that has progressed towards viewing the immune system as numerous components that function together as a whole network. Currently, we are facing significant difficulties in analyzing the data being generated from high-throughput technologies for understanding immune system dynamics and functions, a problem known as the ‘curse of dimensionality’. As the mainstream research in mathematical immunology is based on low-resolution models, a fundamental question is how complex the mathematical models should be? To respond to this challenging issue, we advocate a hypothesis-driven approach to formulate and apply available mathematical modelling technologies for understanding the complexity of the immune system. Moreover, pure empirical analyses of immune system behavior and the system’s response to external perturbations can only produce a static description of the individual components of the immune system and the interactions between them. Shifting our view of the immune system from a static schematic perception to a dynamic multi-level system is a daunting task. It requires the development of appropriate mathematical methodologies for the holistic and quantitative analysis of multi-level molecular and cellular networks. Their coordinated behavior is dynamically controlled via distributed feedback and feedforward mechanisms which altogether orchestrate immune system functions. The molecular regulatory loops inherent to the immune system that mediate cellular behaviors, e.g. exhaustion, suppression, activation and tuning, can be analyzed using mathematical categories such as multi-stability, switches, ultra-sensitivity, distributed system, graph dynamics, or hierarchical control. GB is supported by the Russian Science Foundation (grant 18-11-00171). AM is also supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER grant no. SAF2016-75505-R, the “María de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370) and the Russian Science Foundation (grant 18-11-00171).

Any organism, to survive, must use a variety of defense mechanisms. A relatively recent evolutionary development is that of the adaptive immune system, carried to a quite sophisticated level by mammals. The complexity of this system calls for its encapsulation by mathematical models, and this book aims at the associated description and analysis. In the process, it introduces tools that should be in the armory of any current or aspiring applied mathematician, in the context of, arguably, the most effective system nature has devised to protect an organism from its manifold invisible enemies.

Whole new areas of immunological research are emerging from the analysis of experimental data, going beyond statistics and parameter estimation into what an applied mathematician would recognise as modelling of dynamical systems. Stochastic methods are increasingly important, because stochastic models are closer to the Brownian reality of the cellular and sub-cellular world.