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ESL is rooted in open systems Thermodynamics, shifting the focus from the biology of events to their systemic structure. Models are built on biomedical knowledge, with parameters determined by empirical observation and biophysical constraints, producing simulators that address \u201cwhat if\u201d exploratory questions. We applied this approach to the antigen-specific adaptive immune response as a proof-of-concept of the framework designed to investigate system-level dynamic regime stability and qualitative response to external driving forces. We developed a computational simulator reproducing hallmark features of humoral immunity at daily, monthly and decadal time-scales, including germinal-center dynamics, establishment of long-lived plasma cells, antibody secretion, and long-term decline in the absence of antigen re-exposure. 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