D. Okwan-Duodu, Erik A. Sperling, Edgar G. Engleman
2026.5.1TRENDS IN IMMUNOLOGY
Abstract
The adaptive immune system (AIS) is traditionally viewed as a defensive vertebrate innovation forged by pathogen pressure. Yet many of its core features suggest it is a homeostatic, regulatory circuit, not simply a sophisticated means of antimicrobial warfare. The horizontal transfer of mitochondria--endogenous endosymbiotic organelles-is a conserved mechanism for maintaining tissue homeostasis through metabolic rescue but can alter a cell's identity and provoke immune responses. We propose that escalating multicellular complexity accommodated mitochondrial mobility-and the inevitable intrinsic immunological danger it presents-through a complementary supervisory system with buffering (tolerance), contextualization (specificity), memory, and eliminatory capacities. This perspective reframes the AIS as a constitutive danger management network, integrating tissue homeostasis, metabolic surveillance, immune tolerance, and immunological defense.
Citation format
OKWAN-DUODU, D.; SPERLING, Erik A.; ENGLEMAN, Edgar G. Rethinking the origins and functions of adaptive immunity. TRENDS IN IMMUNOLOGY, 2026.