Computers in Biology and Medicine 31 (2001) 303–331 www.elsevier.com/locate/compbiomed Design and implementation of an immune system simulator M. Bernaschi a ; ∗ , F. Castiglione b a Istituto Applicazioni Calcolo, CNR, V.le Policlinico 137, 00161 Roma, Italy b Center for Applied Computer Science (ZAIK), University of Cologne, Weyertal 80, D-50931 K oln, Germany Received 10 August 2000; accepted 13 March 2001 Abstract Cellular automata based models have proven capable of providing several new insights into the dynamics of the immune system (IS) response. A qualitative picture of the IS behavior can be obtained with small-scale simulations. However, for a more detailed analysis and to further validate the models, large-scale simulations are required. To this purpose we present here a simulator (PARIMM) of the IS response which has been carefully designed and coded to allow such simulations (millions of cells with a very high degree of complexity). The code does not just resort to parallel processing to run faster. Data structures and I= O have been optimized as well to limit the (huge) memory and disk space requirements. The recent addition of the description of the T killer cellular mediated response allows the code to simulate both humoral and cellular immune reactions. All these features put PARIMM among the most complete simulators of the immune system developed up today. c  2001 Elsevier Science Ltd. All rights reserved. Keywords: Immune system; Parallel computing; Cellular automata 1. Introduction The immune system (IS) can be viewed as a classic system of coupled components with birth, death, and interaction among dierent entities. From this viewpoint it looks ideal for a model based on dierential equations and it is not surprising that, in the past, a number of such models have been proposed [1]. However, much caution is required applying continuous models since the IS is composed of discrete cells and antibody molecules. Although the total number of entities is very large, there are many dierent species, so the actual number of any one species may be not so great. * Corresponding author. Tel.: +39-06-88470229; fax: +39-06-88470229. E-mail addresses: massimo@iac.rm.cnr.it (M. Bernaschi), lippo@zpr.uni-koeln.de (F. Castiglione). 0010-4825/01/$-see front matter c  2001 Elsevier Science Ltd. All rights reserved. PII:S0010-4825(01)00011-7