Most biological rates and times decrease systematically with organism body size. We use an ordinary differential equation (ODE) model of West Nile Virus in birds to show that pathogen replication rates decline with host body size, but natural immune system (NIS) response rates do not change systematically with body size. This is surprising since the NIS has to search for small quantities of pathogens through larger physical spaces in larger organisms, and also respond by producing larger absolute quantities of antibody in larger organisms. We call this scale-invariant detection and response. We hypothesize that the NIS has evolved an architecture to efficiently neutralize pathogens. We investigate a range of architectures using an Agent Based Model (ABM). We find that a sub-modular NIS architecture, in which lymph node number and size both increase sublinearly with body size, efficiently balances the tradeoff between local pathogen detection and global response using antibodies. This leads to nearly scale-invariant detection and response, consistent with experimental data. Similar to the NIS, physical space and resources are also important constraints on Artificial Immune Systems (AIS), especially distributed systems applications used to connect low-powered sensors using short-range wireless communication. We show that AIS problems, like distributed robot control, will also require a sub-modular architecture to efficiently balance the tradeoff between local search for a solution and global response or proliferation of the solution between different components. This research has wide applicability in other distributed systems AIS applications.