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Record W4414751547 · doi:10.1101/2025.07.16.663927

Dynamical model and geometric insights in the discontinuity theory of immunity

2025· preprint· en· W4414751547 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldEngineering
TopicArtificial Immune Systems Applications
Canadian institutionsMila - Quebec Artificial Intelligence InstituteMcGill UniversityUniversité de Montréal
Fundersnot available
KeywordsDiscontinuity (linguistics)Immune systemInvariant (physics)Dynamical systems theoryStimulus (psychology)Immunity

Abstract

fetched live from OpenAlex

The immune system's most basic task is to decide what is "self" and "non-self", but a precise definition of self versus non-self remains challenging. According to the discontinuity theory of immunity, effector responses depend on how quickly an antigenic stimulus changes: rapid change triggers an immune response, whereas gradual change fosters tolerance. We present a model of adaptive immune dynamics including T cells, Tregs and cytokines that reproduces the hallmarks of the discontinuity theory. The model allows for sharp discrimination between acute and chronic infections based on the growth rate of the immune challenge, and vaccination-like acute dynamics upon presentation of a bolus of immune challenge. We further show that the model behavior only depends on a handful of testable assumptions that we map to geometric constraints in phase space. This suggests that the model properties are generic and robust across alternative mechanistic details. We also examine the impact of multiple concurrent immune challenges in this model, and demonstrate the occurrence of dynamical antagonism, wherein, in some parameter regimes, slow-growing challenges hinder acute responses to fast-growing ones, with further counter-intuitive behaviors for sequential co-infections. Together, these results place the discontinuity theory on firm mathematical footing and encourage further investigation of interferences of multi-agent immune challenges, from chronic viral co-infections to cancer immunoediting.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.672
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.216
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it