Mathematical Models And Immune Cell Biology

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.

In many respects, biology is the new frontier for applied mathematicians. This book demonstrates the important role mathematics plays in the study of some biological problems. It introduces mathematicians to the biological sciences and provides enough mathematics for bioscientists to appreciate the utility of the modelling approach. The book presents a number of diverse topics, such as neurophysiology, cell biology, immunology, and human genetics. It examines how research is done, what mathematics is used, what the outstanding questions are, and how to enter the field. Also given is a brief historical survey of each topic, putting current research into perspective. The book is suitable for mathematicians and biologists interested in mathematical methods in biology.

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.

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.

This collection of papers offers a broad synopsis of state-of-the-art mathematical methods used in modeling the interaction between tumors and the immune system. These papers were presented at the four-day workshop on Mathematical Models of Tumor-Immune System Dynamics held in Sydney, Australia from January 7th to January 10th, 2013. The workshop brought together applied mathematicians, biologists, and clinicians actively working in the field of cancer immunology to share their current research and to increase awareness of the innovative mathematical tools that are applicable to the growing field of cancer immunology. Recent progress in cancer immunology and advances in immunotherapy suggest that the immune system plays a fundamental role in host defense against tumors and could be utilized to prevent or cure cancer. Although theoretical and experimental studies of tumor-immune system dynamics have a long history, there are still many unanswered questions about the mechanisms that govern the interaction between the immune system and a growing tumor. The multidimensional nature of these complex interactions requires a cross-disciplinary approach to capture more realistic dynamics of the essential biology. The papers presented in this volume explore these issues and the results will be of interest to graduate students and researchers in a variety of fields within mathematical and biological sciences.

Interest in theoretical biology is rapidly growing and this 1981 book attempts to make the theory more accessible to experimentalists. Its primary purpose is to demonstrate to experimental molecular and cellular biologists the possible usefulness of mathematical models. Biologists with a basic command of calculus should be able to learn from the book what assumptions are implied by various types of equations, to understand in broad outline a number of major theoretical concepts, and to be aware of some of the difficulties connected with analytical and numerical solutions of mathematical problems. Thus they should be able to appreciate the significance of theoretical papers in their fields and to communicate usefully with theoreticians in the course of their work.

Mathematical Modeling and Immunology An enormous amount of human effort and economic resources has been directed in this century to the fight against cancer. The purpose, of course, has been to find strategies to overcome this hard, challenging and seemingly endless struggle. We can readily imagine that even greater efforts will be required in the next century. The hope is that ultimately humanity will be successful; success will have been achieved when it is possible to activate and control the immune system in its competition against neoplastic cells. Dealing with the above-mentioned problem requires the fullest pos sible cooperation among scientists working in different fields: biology, im munology, medicine, physics and, we believe, mathematics. Certainly, bi ologists and immunologists will make the greatest contribution to the re search. However, it is now increasingly recognized that mathematics and computer science may well able to make major contributions to such prob lems. We cannot expect mathematicians alone to solve fundamental prob lems in immunology and (in particular) cancer research, but valuable sup port, however modest, can be provided by mathematicians to the research aspirations of biologists and immunologists working in this field.

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).