Some common systems modelling and simulation approaches for immune problems are Monte Carlo simulations, system dynamics, discrete-event simulation and agent-based simulation. These methods, however, are still not widely adopted in immunology research. In addition, to our knowledge, there is few research on the processes for the development of simulation models for the immune system. Hence, for this work, we have two contributions to knowledge. The first one is to show the importance of systems simulation to help immunological research and to draw the attention of simulation developers to this research field. The second contribution is the introduction of a quick guide containing the main steps for modelling and simulation in immunology, together with challenges that occur during the model development. Further, this paper introduces an example of a simulation problem, where we test our guidelines.

"Taken together, the body of information contained in this book provides readers with a bird’s-eye view of different aspects of exciting work at the convergence of disciplines that will ultimately lead to a future where we understand how immunity is regulated, and how we can harness this knowledge toward practical ends that reduce human suffering. I commend the editors for putting this volume together." –Arup K. Chakraborty, Robert T. Haslam Professor of Chemical Engineering, and Professor of Physics, Chemistry, and Biological Engineering, Massachusetts Institute of Technology, Cambridge, USA New experimental techniques in immunology have produced large and complex data sets that require quantitative modeling for analysis. This book provides a complete overview of computational immunology, from basic concepts to mathematical modeling at the single molecule, cellular, organism, and population levels. It showcases modern mechanistic models and their use in making predictions, designing experiments, and elucidating underlying biochemical processes. It begins with an introduction to data analysis, approximations, and assumptions used in model building. Core chapters address models and methods for studying immune responses, with fundamental concepts clearly defined. Readers from immunology, quantitative biology, and applied physics will benefit from the following: Fundamental principles of computational immunology and modern quantitative methods for studying immune response at the single molecule, cellular, organism, and population levels. An overview of basic concepts in modeling and data analysis. Coverage of topics where mechanistic modeling has contributed substantially to current understanding. Discussion of genetic diversity of the immune system, cell signaling in the immune system, immune response at the cell population scale, and ecology of host-pathogen interactions.

This book constitutes the refereed proceedings of the 11th International Conference on Artificial Immune Systems, ICARIS 2012, held in Taormia, Italy, in August 2012. The 19 revised selected papers presented were carefully reviewed and selected for inclusion in this book. In addition 4 papers of the workshop on bio and immune inspired algorithms and models for multi-level complex systems are included in this volume. Artificial immune systems (AIS) is a diverse and maturing area of research that bridges the disciplines of immunology, biology, medical science, computer science, physics, mathematics and engineering. The scope of AIS ranges from modelling and simulation of the immune system through to immune-inspired algorithms and in silico, in vitro and in vivo solutions.

The book describes a computational model of the immune system reaction, C-ImmSim, built along the lines of the computer model known as the Celada-Seiden model (CS-model). The computational counterpart of the CS-model is called IMMSIM which stands for IMMune system SIMulator. IMMSIM was written in 1992 by the physicist Phil E. Seiden and the immunol

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.

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).

Computational immunology offers in silico strategies for understanding of complex processes occurring in the natural immune system of a living organism that are difficult to explore by traditional in vivo or in vitro techniques. The monograph introduces conceptual languages and approaches for modelling biological processes. The Agent Modelling Language is investigated for conceptualisation of immune processes. AML-based diagrams represent properties and processes occurring in a lymph node.