Smarsly, KayKaySmarsly2026-05-112026-05-112026-04-22IEEE Access (in Press): (2026)https://hdl.handle.net/11420/62976Structural health monitoring (SHM) has become a central tool for managing civil infrastructure. In modern SHM, the physical structure and the SHM system together form a coupled cyber-physical system. Due to the networked nature of the cyber-physical system, threat categories no longer only comprise anomalies in the physical structure or internal SHM system faults, but also external cyberattacks. The combination of all capabilities required to withstand such threats can be subsumed under the term “digital immune system”. This paper proposes a biologically inspired, computing-oriented reference architecture for digital immune systems for civil infrastructure. The reference architecture is derived from an analysis of the functions and components of the biological immune system, following a design science research methodology grounded in structured functional abstraction. The paper presents a descriptive, architecture-level formal specification of the reference architecture and threat categorization, thereby providing a rigorous conceptual foundation for future modeling and simulation of digital immune systems in cyber-physical SHM. The formalization defines structural constraints of the reference architecture without imposing implementation-specific correctness criteria. To illustrate operational plausibility without prescribing a concrete implementation, the paper additionally presents an illustrative use-case scenario based on an existing SHM test setup. The paper concludes with recommendations for implementing and validating digital immune systems in real SHM deployments. Overall, digital immune systems have the potential to enhance the resilience of cyber-physical SHM systems for civil infrastructure and to stimulate interdisciplinary research at the interface of civil engineering, computer science, and immunology.en2169-35362026Institute of Electrical and Electronics Engineers Inc.https://creativecommons.org/licenses/by/4.0/artificial immune systemscivil engineeringcyber-physical systemsfault diagnosisStructural health monitoringTechnology::624: Civil Engineering, Environmental Engineering::624.1: Structural EngineeringComputer Science, Information and General Works::005: Computer Programming, Programs, Data and Security::005.8: Computer SecurityJournal Articlehttps://doi.org/10.15480/882.1706710.1109/ACCESS.2026.368667710.15480/882.17067