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# Self or nonself: end of a dogma?

## Details

**Authors** Duhamel, Marie and Salzet, Michel

**Year** 2025

**Publisher** Frontiers in Immunology

**Kind of work** article

**Discipline** Medicine

**Secondary disciplines** Biology

**Applied** false

[Read it at the publisher](https://doi.org/10.3389/fimmu.2025.1595764) 
10.3389/fimmu.2025.1595764

## In authors' words

### What they set out to do (purpose)

To review whether the self/nonself model of immunity, dominant from roughly 1950 to the early 1980s, still holds as the organizing principle of immunology.

### Who or what was studied (sample)

A narrative review of the immunological literature from the early twentieth century to the present, including Burnet's clonal selection theory, Janeway's pattern recognition, Matzinger's danger model, Pradeu's continuous immune self, and work on trained immunity.

### How they did it (methods)

Mini review organized historically: foundations before mid-century, mid-century codification of the self-nonself paradigm, challenges to it, and an integrative synthesis.

### What they found (results)

The authors conclude that the boundary between self and nonself is neither absolute nor permanent but is dynamically regulated. Maternal-fetal tolerance, microchimerism, commensal microbiota and the virome, trained innate immunity, and damage signaling show that immune responses depend less on foreignness than on context. Self/nonself reasoning remains useful in transplantation and autoimmunity. The authors describe the field as in a period of revision and expansion toward a contextual, integrative model.

## Commentary

### In short

A review of how immunology's long-standing rule that the body attacks the foreign and tolerates the self gave way to a view in which the response depends on developmental, microbial and damage context.

### Response

The review traces the replacement of a single self/nonself boundary with a context-dependent one, which bears most directly on distinctions: where the line is drawn changes with developmental stage, microbial partners and tissue state, and the authors keep the line as a working tool for transplantation and autoimmunity. Perspectives enter because the same cell or antigen is tolerated or attacked depending on the vantage of the responding system and its context. Relationships carry weight in the microbiome and danger-signal accounts, where immune function is explained by interactions with commensals and damaged tissue. Caveats: this is a narrative mini review rather than an empirical test, and the authors do not formalize the patterns; the perspective reading is an interpretation of their emphasis on context.

**Patterns it shows** D, R, P

Shows the structure is there

**Added** 2026-10-26

**How to cite this** Duhamel, Marie and Salzet, Michel (2025). Self or nonself: end of a dogma?. Frontiers in Immunology.