il modello IMMSIM

Dal Cofin 1999 al cofin 2001

obiettivi IMMSIM cofin99

• Il modello IMMSIM per studio risposta VACCINI

• implementazione ramo cellulare e analisi competizione/cooperazione rami umorale cellulare

• verifica della capacita’ di simulare risposte a un vaccino pur con un modello semplificato di memoria e virus

• Lo sviluppo di una nuova versione del modello, IMMSIM-C

• rendere disponibile a tutti il modello, per uso scientifico e didattico

• aumentare le capacita di verifica e di arricchimento del modello

programma IMMSIM cofin99

• Adeguamento modello IMMSIM per studio risposta VACCINI

• inserimento della risposta cellulare (in linguaggio APL)

• modellazione virus• analisi interazioni risposta

umorale e cellulare al virus

• Sviluppo nuova versione del modello IMMSIM-C

• scrittura codice simulazione a partire dal modello

• verifica risposte a stimoli standard

• realizzazione interfaccia utente

Problemi

• Vaccini in IMMSIM

• vaccinazione poco efficace sulla risposta cellulare

• problemi generali del modello nel simulare la memoria specie nella risposta cellulare

• Philip Seiden

• IMMSIM-c

• da progetto parallelo a versione principale del simulatore

• difficolta’ allineamento risposta umorale

• necessita’ modifica modello risposta cellulare

Attivita’ effettiva IMMSIM-c

• CODICE• completamento

versione “beta”

• test risposte standard

• realizzazione interfaccia utente

• MODELLO• modifica e

aggiornamento modello Tc (Ahmed)

• campo di validita e modalita di uso

• allargamento collaborazioni immunologi, matematici e fisici

• DIDATTICA• interfaccia utente

• esperienza nei corsi didattica opzionale 99 (Univ.Genova)

• collaborazione per uso nei corsi immunologia (Univ.Princeton)

• IMMSIM-c v.070

• IMMSIM-c v050 risposta umorale ad antigene

• modeling cellular response in IMMSIM-c

•IMMSIM-c v070 vaccination test1

•IMMSIM-c v0.60 vaccination tests

Warning and conclusions (ACRI 2001 Puzone-Celada)

….the other side of the medal, there is the following problem: the large number of parameter settings required to reach a satisfactory tuning and the easy manipulation of them, may cause the danger of an "ad hoc", incorrect tuning of the automaton.This danger is shared by most models that have a certain degree of complexity like IMMSIM has, with many actors and interaction rules. We feel it as our duty to help readers/users avoid this danger when getting their hands on IMMSIM. For this reason we are listing some usage recommendations, to be appended to the user's manuals.

1-The param pool (e.g. lifetimes, populations' balance, receptor pool sizes, etc) should be tuned in such a way as to obtain biologically-credible responses to typical immunological stimulations, keeping both the values imposed and the result obtained, within biologically acceptable limit and congruent with each other.

2-Contribution to hypothesis testing should be then made simulating experiments by introducing

appropriate param/values/conditions in the tuned model, and observing the resulting modifications of the response and eventually looking at the behaviors of the single sections of the model (e.g. humoral only or cellular only, etc).

3-The more interesting results from step 2, (if any: the model may not be adequate to simulate a

given hypothesis) should be tested for possible artifacts due to the model implementation. This requires to understand which model characteristics are more responsible for the results, and to seek possible corresponding biological mechanisms. Sometimes it will be advisable to go back to step 1 and try to retune the model and correct/enhance the interesting result.

4-The conclusions and suggestions emerging from point 3 should be discussed with immunologists and experimental verification should be set up via in vivo/in vitro tests.

Failing to perform these steps correctly may easily yield useless or even totally wrong results, and eventually total absence of productivity/predictivity of the model.

•IMMSIM in the courses at Princeton