Abstract. The Immune System is, together with Central Nervous System, one of the most important and complex unit of our organism. Despite great advances in recent years that shed light on its understanding and in the unraveling of key mechanisms behind its functions, there are still many areas of the Immune System that remain object of active research. The development of in-silico models, bridged with proper biological considerations, have recently improved the understanding of important complex systems [1,2]. In this paper, after introducing major role players and principal functions of the mammalian Immune System, we present two computational approaches to its modeling; i.e., two insilico Immune Systems. (i) A large-scale model, with a complexity of representation of 10 6 − 10 8 cells (e.g., APC, T, B and Plasma cells) and molecules (e.g., immunocomplexes), is here presented, and its evolution in time is shown to be mimicking an important region of a real immune response. (ii) Additionally, a viral infection model, stochastic and light-weight, is here presented as well: its seamless design from biological considerations, its modularity and its fast simulation times are strength points when compared to (i). Finally we report, with the intent of moving towards the virtual lymph note, a cost-benefits comparison among Immune System models presented in this paper.G. Stracquadanio, R. Umeton, et al.