Nelson Monteiro Vaz is retired Professor of Immunology at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. He will be 75 next September. At NYU, with Bernard Levine, he devised a method of inducing prolonged intense IgE responses in mice at the beginning of the 1970s. This led them to stumble onto Ir genes. At CARIH, in Denver, he again stumbled onto “oral tolerance,” met Francisco Varela and started to believe that everything in immunology was upside down. He then returned to Brazil where he has been ever since, except for short periods in Antonio Coutinho’s laboratories in Paris and Oeiras, working on “oral tolerance,” natural immunoglobulins, and theoretical immunology in the 1990s and 2000s. He believes that contact between immunology and cognitive sciences will be beneficial to both.
Pordeus V., Ramos G. C., Carvalho C. R., Castro Jr. A. B., Cunha A. P. & Vaz N. M. (2009) Immunopathology and oligoclonal T cell expansions. Observations in immunodeficiency, infections, allergy and autoimmune diseases. Current Trends in Immunology 10: 21–29. Fulltext at https://cepa.info/357
In traditional descriptions immunological activity is neither systemic nor historical and is never “physiological.” Since it is dominated by reductionist, teleological and cognitivist approaches. After deconstructing hegemonic immunology way of seeing, we proposed previously a constructivist explanation to immunological physiology, namely, The Conservative Physiology of the Immune System (Vaz NM Clin Dev Immunol 2006), theory based on our own experimental evidences and referenced on Humberto Maturana’s Biology of Cognition. In this paper we propose an immanent mechanism for immunological pathophysiology and disease development.
Vaz N. M. (2011) Francisco Varela and the immunological self. Systems Research and Behavioral Science 28: 696–703. Fulltext at https://cepa.info/4220
Francisco Varela, a leading neurobiologist and cognitive scientist, made a 10-year-long incursion into immunology. His in-depth contributions aimed to develop a systemic description to replace the standard stimulus/response/regulation scaffold that has governed immunology since its inception in the 19th century. Many of these efforts involved expansions of the notions introduced by Niels Jerne in his idiotypic network theory (Jerne, 1974a, 1974b) with the added notion of organizational closure, derived from the autopoietic theory. However, today, just like yesterday, the immunological community remains inclined to neglect these efforts and instead rests satisfied with half-a-century old clonal selection concepts (Burnet, 1959).
Vaz N. M. (2011) The Enactive Paradigm 33 Years Later. Response to Alfred Tauber. Constructivist Foundations 6(3): 345–351. Fulltext at https://cepa.info/219
Upshot: According to Biology of Cognition and Language (Maturana’s approach) the immune system is not a cognitive system and defining of a cognitive paradigm is not what we understand as a Maturanian approach to immunology. The true cognitive actions in immunology are performed by immunologists acting as observers, not by body organs or systems. Stimuli and responses are not adequate concepts in the description of systems. As a closed network of cellular/molecular interactions, the immune system yields patterns of activity as is transparent in robust conserved profiles of reactivity of natural immunoglobulins, as investigated by Nóbrega et al. and Cohen et al., which offer the opportunity to unravel its natural, spontaneous activity. Dietary materials, products of the commensal microbiome are the most abundant and common elements continuously incorporated to the network activity and, thus, also represent an important avenue of investigation.
Vaz N. M. (2011) The Specificity of Immunologic Observations. Constructivist Foundations 6(3): 334–342. Fulltext at https://cepa.info/217
Context: Immunity includes cognitive concepts: the organism is thought to specifically recognize foreign materials and develop a memory of these encounters. Vaccines are thought to work by enhancing this immunological memory. Lymphocytes are key cells and specific antibodies are key molecules in immune recognition. Antibodies are blood proteins called “immunoglobulins.” Spontaneously formed immunoglobulins are seen as “natural” antibodies to dietary components and commensal bacteria. Immune cognition is used simply as a didactic metaphor. Problem: Do the cognitive aspects of immunology stem from the activities of cells and molecules, or are they ascribed by the immunologist operating as a human observer? (1) An immense variety of immunoglobulins may bind to the same antigen with different binding energies. It is the immunologist who arbitrates the boundary between those that are specific (and declared antibodies) and those that are not. Specific antibodies serve as functional labels pasted onto natural immunoglobulins, as if they were recognizing elements. Is this “arbitration” the true cognitive event ascribed to immunoglobulins and lymphocytes? (2) A major impasse exists between progress in experimental immunology and its translation into clinical results. A proper understanding of immunological activity demands a wider view of an organism’s biology and, also, of the interference of human observers in delineating experimental realities, such as the specificity of immune recognition. Maturana’s biology of cognition and language provides one such approach. Method: Use of Maturana’s biology of cognition and language concepts to describe immunological activity. Results: A whole new understanding of immunological activity is suggested. Implications: A major change in the way of seeing is proposed that may eventually help the translation of this knowledge into clinical results. Furthermore, the immune system may also become a proper model for cognitive analyses.
Vaz N. M. & Botelho Andrade L. A. (2017) Authors’ Response: Not Objective, Not Subjective - Something Else: Coordination of Actions. Constructivist Foundations 13(1): 154–159. Fulltext at https://cepa.info/4424
Upshot: Mpodozis and Maturana endorsed our way of seeing and enrich the debate, offering their own arguments. Stewart and Cohen criticize some points of our article. Stewart thinks that we are “watering down” Varela’s enactivism and approaching objectivism; we show why this is not what we believe. Cohen offers a long (generous) description of his own functional idea of immunological activity and we show why our positions are incommensurable; agreeing with Mpodozis’s comment, we claim that nothing is gained by ascribing cognitive properties to immunological activity.
Vaz N. M. & Botelho Andrade L. A. (2017) The Epigenetic Immune Network. Constructivist Foundations 13(1): 141–146. Fulltext at https://cepa.info/4419
Context: The dominant theory in immunology is straight neo-Darwinian, almost 60 years old and does not address its epigenetic foundation. In traditional immunology, cognitive notions are used only as metaphors: Cognitive notions derived from enaction (Varela) and biology of cognition (Maturana) may be applied to immunology. Problem: Why is there a huge gap between the rapidly growing knowledge in experimental immunology and applying this knowledge to medical issues? Could the difficulty be conceptual? Method: We review the history of Varela’s involvement in immunology to contribute to the genealogical and cartographic understanding of his work, and we highlight the key questions that still need to be addressed. Results: From our perspective, a phenomenon known as “oral tolerance” (stabilization of immune activity in relation to dietary and microbiota antigens) is crucial in the promotion of a change in paradigms. Applying non-metaphorical approaches to what is traditionally understood as immune cognition can be of great theoretical importance. For example, computer simulations of immunological activity were able to predict experimental results on oral tolerance. Reciprocally, experimental results, for example, the (adoptive) transfer of “oral tolerance” with mouse T lymphocytes, is critically important for immunological theory: “tolerance” understood as non-responsiveness cannot be transferred, thus it must be seen as an active phenomenon. Implications: The article emphasizes the importance of Varela (and his collaboration with Coutinho and Stewart, in Paris) for the development of immunological theory. Constructivist content: The organism, as a whole, is not a biochemical listing of properties, or the result of a genetic program but it is rather a process of continuous construction and maintenance.
Vaz N. M., Ramos G. C., Pordeus V. & Carvalho C. R. (2006) The conservative physiology of the immune system: A non-metaphoric approach to immunological activity. Clinical and Developmental Immunology 13(2–4): 133–142. Fulltext at https://cepa.info/6357
Historically, immunology emerged as a biomedical science, concerned with host defense and production of anti-infectious vaccines. In the late 50s, selective theories were proposed and from then on, immunology has been based in a close association with the neo-Darwinian principles, such as random generation of variants (lymphocyte clones), selection by extrinsic factors (antigens) – and, more generally, on genetic determinism and functionalism. This association has had major consequences: (1) immunological jargon is full of “cognitive” metaphors, founded in the idea of “foreignness”; (2) the immune system is described with a random clonal origin, coupled to selection by random encounters; and (3) physiological events are virtually absent from immunological descriptions. In the present manuscript, we apply systemic notions to bring forth an explanation including systemic mechanisms able to generate immunological phenomena. We replace “randomness plus selection” and the notion of foreignness by a history of structural changes which are determined by the coherences of the system internal architecture at any given moment. The importance of this systemic way of seeing is that it explicitly attends to the organization that defines the immune system, within which it is possible to describe the conservative physiology of the immune system. Understanding immune physiology in a systemic way of seeing also suggests mechanisms underlying the origin of immunopathogeny and therefore suggests new insights to therapeutic approaches. However, if seriously acknowledged, this systemic/historic approach to immunology goes along with a global conceptual change which modifies virtually everything in the domain of biology, as suggested by Maturana.