The Invisible Lens: Why Theoretical Models Are Essential for Interpreting Immune Phenomena.

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.