1st Edition
Immune System Modelling and Simulation
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
Repertoires
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
Suicide
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
Maturity
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
Anergy
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
Exhaustion
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
Bibliography
Biography
Filippo Castiglione, Franco Celada
