Artificial Immune Systems, 8th International Conference, ICARIS 2009, York, UK, August 9-12, 2009. Proceedings

Many emerging pathogens infect multiple host species [1], and multi-host pathogens may have very different dynamics in different host species [2]. This research addresses how pathogen replication rates and Immune System (IS) response times are constrained by host body size. An Ordinary Differential Equation (ODE) model is used to show that pathogen replication rates decline with host body size but IS response rates remain invariant with body size. An Agent-Based Model (ABM) is used to investigate two models of IS architecture that could explain scale invariance of IS response rates. A stage structured hybrid model is proposed that strikes a balance between the detailed representation of an ABM and computational tractability of an ODE, by using them in the initial and latter stages of an infection, respectively. The Immune System (IS) solves a search problem in both physical space and antigen space. The length of the search is determined by the time it takes for a cognate B-cell to encounter antigen. Our research suggests that this time is independent of the size of the organism [3]. This is counter-intuitive, since if we inject a sparrow and a horse with the same amount of antigen, the immune system of the horse has to search a larger physical space to find the pathogen, compared to the sparrow. This research attempts to explain how the time for the IS to search for antigen is independent of the size of the organism. In addition to the immune system having to search larger spaces in larger organisms, larger body size can slow viral growth and immune system response times because the metabolic rate of cells is lower in larger species [4]. The metabolic rate of each cell is constrained by the rate at which nutrients and oxygen are supplied by the cardiovascular network. The rate at which this network supplies nutrients to each cell scales as the body mass (M) raised to an exponent of -1/4: Bcell M , such that individual cellular metabolic rates decrease as the body mass increases. The metabolic rate of a cell dictates the pace of many biological processes [4,5]. Metabolic rate is hypothesized to slow the speed of cell movement and proliferation in larger organisms. This could affect IS search times by reducing movement and proliferation of immune cells [6]. Rates of DNA and protein synthesis are also dependent on the cellular metabolic rate and could influence the rate at which pathogens replicate inside infected cells [2]. These two hypotheses, that IS search times and pathogen replication rates slow proportional to cellular metabolic rate and M, lead to 4 possibilities, shown in Table 1 as originally proposed by Wiegel and Perelson [6].