Context-Dependent Signal Interpretation in Immunology: Implications for Dynamic Systems Models of Disease

This paper examines how immunological signals, such as cytokines, demonstrate context-dependent behavior that cannot be explained by static interpretation frameworks. Evidence from cytokine modulation and neuro-immune interactions shows that identical signals may carry different meanings depending on system state and coupling. Building on this, the paper introduces a dynamic systems interpretation, where signal meaning is understood as a function of system dynamics rather than intrinsic properties. The Universal Resonance Model (URM) is presented as a unifying framework that integrates these observations and explains how changes in variance, autocorrelation, and recovery reflect transitions in biological systems. As part of the URM Validation Series (Paper 12), this work provides converging evidence that supports a shift from static biomarker interpretation toward trajectory-based and state-dependent clinical reasoning.