Systems Human Immunology and AI: Immune Setpoint and Immune Health.

The immune system, critical for human health and implicated in many diseases, defends against pathogens, monitors physiological stress, and maintains tissue and organismal homeostasis. It exhibits substantial variability both within and across individuals and populations. Recent technological and conceptual progress in systems human immunology has provided predictive insights that link personal immune states to intervention responses and disease susceptibilities. Artificial intelligence (AI), particularly machine learning (ML), has emerged as a powerful tool for analyzing complex immune data sets, revealing hidden patterns across biological scales, and enabling predictive models for individualistic immune responses and potentially personalized interventions. This review highlights recent advances in deciphering human immune variation and predicting outcomes, particularly through the concepts of immune setpoint, immune health, and use of the immune system as a window for measuring health. We also provide a brief history of AI; review ML modeling approaches, including their applications in systems human immunology; and explore the potential of AI to develop predictive models and personal immune state embeddings to detect early signs of disease, forecast responses to interventions, and guide personalized health strategies.