1st Edition

Immune System Modelling and Simulation

By Filippo Castiglione, Franco Celada Copyright 2015
    288 Pages 52 Color & 24 B/W Illustrations
    by CRC Press

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    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 immunologist Franco Celada. This model was built around the idea of developing a computerized system to perform experiments similar in vivo experiments; a tool developed to help biologists testing theories and hypothesis about how the immune system works.

    C-ImmSim is best viewed as a collection of models in a single program. It incorporates the principal core facts of today’s immunological knowledge, such as the diversity of specific elements, MHC restriction, clonal selection, thymic education of T cells, antigen processing and presentation (both the cytosolic and endocytic pathways are implemented), cell-cell cooperation, homeostasis of cells created by the bone marrow, hyper mutation of antibodies, maturation of the cellular and humoral response, and memory. Besides, an antigen can represent a bacterium, a virus, or an allergen or a tumor cell. C-ImmSim has been recently customized to simulate the HIV-1 infection. Moreover, it can simulate the immunotherapy for cancer. These features are all present in the code and people can choose to turn them on and off at compiling time.

    The book presents the basic model as well as the various customizations to implement the description of different diseases and the way they have been used in practice to produce new knowledge either from hypothesis or from lab-experiment data. In this respect, the book can be used as a practical guide to implement a computational model with which to study a specific disease and to try to address realistic clinical questions.

    Immunology for aliens

    Leo Szilard paradox: Grand Central Terminal

    Non-specific defense

    Levels of evolution

    How is a trait selected if it was not needed?

    Luck or foresight?

    Blood brothers

    The members of the winning team are rewarded

    Somatic recombination produces diversity among equals

    The workshop of the adaptive response


    A battalion of one

    Self-inflicted damage threatens survival

    Don’t think, but reason and understand

    Full cover comes at a cost

    A bet, not a fantasy, about earliest happenings

    The cooperation of very different cells multiplies jobs that can be done

    Thymus deeds

    Hypothesis is a bet: Tips for the Aliens

    To grow and to change

    Philosophy storm


    In the beginning

    The linear transmission of activation

    Recipe for complete Freund have them

    An antibody is an antibody (or two?)

    Scientific Myths: God's mess with human cognition

    A monument to interdisciplinarity

    Scientific Myths 2: Apollo roams about the hills of Tennessee

    Plain reasoning breaks the Spell

    Of wolfs, dogs and shepherds

    How to block anti-self

    Controlling self- damage needs structures: the lymphoid organs

    Time of strengthening


    A cognitive system? A floating brain?

    Cellular Automaton makes sense

    Memory is in the numbers

    The power rests with whoever issues regulatory signals

    The seed is prepared during the primary response

    The challenge

    Competition in the minefield of cross reactions

    The compensated immune system wants to understand

    The two immune systems

    The cellular branch confronts a virus infection

    How to model the cellular and the humoral together

    Body and soul, actions and philosophy

    What steps can and should be simulated

    Attrition and cross-reaction

    Memory is strong, sometimes too strong

    IMMSIM reveals MaN (Memory anti Naïve) as a cause of aging

    A course leading to aging of the immune system

    A new challenge for modelers: conformation

    Protein Conformation and the immune system

    Antibody mediated activation of a mutant enzyme

    More fields for models, and where to find them

    A note to encourage cross referencing

    An unconventional glossary for aliens

    Aliens for immunology

    The unusual mix of immunology and computer science

    Classical modeling techniques versus the "new kind of science"

    From spin-like to agent-based models

    The ancestors

    The others

    C-ImmSim unveiled

    Model compartments

    The cells

    The molecules

    The repertoire

    The molecular affinity

    Reshaping the affinity landscape

    Haematopoiesis and cell homeostasis

    The selection of cells in the thymus

    The Hayflick limit

    Cell aging and death

    A (dynamic) immune memory

    The hyper-mutation of antibodies

    Immune activation


    Interactions among entities

    Antigen digestion and presentation

    Cell motion and diffusion of molecules

    Main procedures

    Notes on the expressed repertoire

    Scaling the system size

    Few words on the definition of molecular quanta

    The choice of the MHC molecules

    The parameters

    What to monitor?

    Benchmarks aka qualitative model validation

    Primary and secondary response


    Bacterial Infection

    Viral infection

    Modelling idiotypes and the idiotype network

    Specific applications

    A multi-scale approach to model hypersensitivity

    HIV infection and AIDS

    Immunodominance in cancer immunotherapies

    Embedding immunoinformatics predictions

    One last word



    Filippo Castiglione, Franco Celada