ABSTRACT Immunology progresses not merely by accumulating data but by evolving the conceptual lenses through which those data are interpreted; yet for six decades the self–non‐self/infectious‐non‐self (SNS/INS) paradigm—casting allogeneity as activating signal and ‘self’ as intrinsically tolerogenic—has dominated research design, peer review and curriculum. This, in turn, systematically amplifies concordant findings while attenuating evidence for tissue integrity, metabolic, symbiotic and network‐centric cues. This conceptual monoculture appears as a hidden dogma that impedes breakthroughs in our understanding of the immune system and the development of curative therapies. By institutionalising theoretical immunology as a formal discipline and treating models as explicit, testable tools rather than hidden assumptions, immunologists can sharpen hypothesis generation and achieve a better understanding of existing data. This essay provides an overview of empirically grounded theoretical models to counter monoculture, clarify how frames shape interpretation, and expand the field's conceptual toolkit.
Masoud H. Manjili (Mon,) studied this question.