Immune signal-status misclassification: A theoretical framework for biological status assignment and failed status...

Area of Science:

• Immunology
• Systems Biology
• Computational Biology

Background:

• Immune regulation relies on signal detection and functional status assignment.
• Context, history, and regulatory state critically influence immune responses.
• Existing models imply context-dependent immunity but lack an explicit status-assignment layer.

Purpose of the Study:

• Propose immune signal-status misclassification as a systems-level framework.
• Formalize the concept of a status-assignment layer in immune regulation.
• Explain immune dysfunction as a failure in assigning or resolving signal status.

Main Methods:

• Developed a conceptual framework for immune signal-status misclassification.
• Constructed a minimal toy model to illustrate status maintenance.
• Reanalyzed public transcriptomic data (GEO accession GSE67472) to operationalize the framework.

Main Results:

• Demonstrated how prior danger-status assignment can persist after signal decline.
• Showcased operationalization of immune-status structure using a type-2 inflammatory signature in airway epithelium.
• Derived five falsifiable predictions, including context-history effects and resolution markers.

Conclusions:

• Immune failures can stem from incorrect biological status assignment or failed status resolution.
• The proposed framework offers a new perspective on immune dysregulation.
• Future research should validate predictions regarding context, history, and resolution markers in immune diseases.