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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 OpenAlexaff
Christian Mauffette Denis, Victoria Mochulska, Maya Dagher, Vincent Verbavatz, François X. P. Bourassa, Grégoire Altan‐Bonnet, Paul François

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.002
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicArtificial Immune Systems ApplicationsFrench-language works237,207