title: On the origin of immunopathology.
abstract: Stranded between medicine and experimental biology, immunology is buried in its own problems and remains distant from important areas of current biology, such as evolutionary theory, developmental biology and cognitive sciences. Immunology has treated the living system merely as the place or dimension in which immune activity takes place, inserted on a misleading axis (progressive responsiveness versus no response; memory versus tolerance) which neglects the analysis of a robustly stable dynamics which is always present and is neither tolerance nor immunity-a problem currently approached as one of "regulatory" activity. However, a regulatory response also demands regulation, leading to an endless recursion and the adoption of a stimulus-response framework inevitably drives us away from the physiological processes in which lymphocytes are involved. Herein, we propose that immunological physiology, like everything else in the body is dynamic and conservative. Immunopathology, including inherited immunodeficiencies, severe forms of infectious diseases, allergy and autoimmune diseases, are interferences with this stability which frequently include oligoclonal expansions of T lymphocytes. We suggest that this decrease in clonal diversity results from a loss of the stabilizing connectivity among lymphocytes and are not simply markers of immunopathology, but are rather expressions of basic pathogenic mechanisms. The so-called autoimmune diseases are examples of this disequilibrium. In the last decade the characterization of an enormous and diversified commensal microbiota has posed a new and pressing problem: how to explain the harmonic conviviality with trillions of foreign macromolecules. In addition, robustly stable relations towards macromolecular diet can be established by simple ingestion, a state presently labeled as "oral tolerance", a problem that has been buffered for decades as anti-inflammatory protection of the gut. A major change in terminology is necessary to describe this new panorama. We focus on two important gaps in immunological discussions: (a) the organism, seen simultaneously as the medium with which the immune system is constantly in touch and as the entity that mediates the contact with external materials; and (b) the observer, the immunologist, who operates as a human being in human languaging with other human beings, and characterizes immunological specificity. We acknowledge that we are proposing radical departures from current dogma and that we should justify them. Most of what we propose stem form a way of seeing called Biology of Cognition and Language, that derives from ideas of the neurobiologist/philosopher Humberto Maturana, also known as "autopoiesis theory".
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. Electronic address: nvaz@icb.ufmg.br.
authors.forename: Nelson M
authors.initials: NM
authors.lastname: Vaz
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, MG, Brazil.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005075:Biological Evolution; D044127:Epigenesis, Genetic; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007109:Immunity / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D051381:Rats; D049490:Systems Biology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007073:Immunoglobulin E
keywords: Cognition; Observer; Oligoclonality; Organism; Systems