Biology of Cognition
The Enactive Paradigm33 Years Later Nelson M. Vaz
But assimilation into what? Here, what is missing is the definition of the invariant, conservative organization of the immune system (Vaz et al. 2003; 2006; Pordeus et al. 2009).
Appendix 1: On Coutinho/ Varela/Stewart In the 1980–90s, Coutinho and coworkers produced a tremendous amount of experimental evidence in support of the network theory, evidence that cannot be explained by clonal concepts. I have selected just one of their publications per year in that decade to show this: minute amounts of IgM would trigger the production of many more immunogloblulins with the same specificity (Forni et al. 1980); suppression of a recurrent idiotype resulted in profound alterations of the whole B cell compartment (Bernabé et al. 1981); pretreatment of newborn mice with idiotypes also triggered changes in T cells (Holmberg, Ivars & Coutinho 1983); idiotypic determinants of natural IgM antibodies resemble self MHC determinants (Holmberg et al. 1984); there is a high frequency of natural autoantibodies in normal newborn mice (Dighiero et al. 1985); the high idiotypic connectivity of “natural” newborn antibodies is not found in adult mitogen-reactive B cell repertoires (Holmberg et al. 1986); autonomous activation of B and T lymphocytes also takes place in antigen-free mice (Pereira et al. 1986); (Ir-gene) low-responders could be turned into high-responders by manipulation of the developing immune system using antibodies’ (Martinez et al. 1987); the “natural” autoreactive B cell activation in the spleen of normal mice is Tcell dependent (Huetz et al. 1988); transplantation tolerance correlates with high levels of T and B lymphocyte activity (Bandeira et al. 1989). None of this can be explained by the expansion of isolated clones of lymphocytes, but Jerne’s theory lacked the concepts to
pull together all this evidence in a coherent framework. After Varela’s interventions, Coutinho’s laboratory published several important theoretical papers and further experimental evidence, such as: 1 | measuring the serum concentrations of four natural IgM antibodies, two of which showed idiotypic complementarity in in vitro assays, the injection of nanograms of these idiotypes triggered long-lasting changes in other idiotypes (Lundqvist et al. 1989); 2 | idiotypes in normal human sera and in patients with autoimmune diseases had different patterns of fluctuation (Varela et al. 1991); 3 | treatment by infusion with high doses of intravenous immunoglobulins (IVIg) was correlated with regaining normal patterns of idiotypic connectivity (Dietrich et al. 1993). A most relevant development was the introduction of “global” methods of analysis of antibody repertoires using a modified immunoblot (Nóbrega et al. 1993). This was also directed at the analysis of “spontaneous” lymphocyte activation, but had the additional merit of looking into immunoglobulin populations instead of analyzing “specific” clonal reactions. The “profiles” of reactivity generated by these “global” methods, subsequently much expanded by Cohen and co-workers (Madi et al. 2011), are “snapshots” of network dynamics that open up the possibility of observing a large sector of the immune system instead of clones that react with a defined antigen.
Appendix 2: On Cohen
tity that processes information from body tissues and the external medium, computes what is best for inflammation control in each organ, and decides which cells should be activated, etc. This is classic cognitivism: the connectionist side emerges as a systemic (collective) action of otherwise isolated cells. For Maturana, the distinction of a system is something made by a human observer that draws the limits of an entity, sees the invariance of its organization, and identifies it as a member of a class of systems. In this sense, Cohen’s homunculus derives from the organization of immune systems and would display the same patterns in every organism. Computing the inflammatory status of tissues and organs lacks a parallel in Maturana because it depends of the computer metaphor of living networks. However, computers follow their programs, whereas living systems follows their internal dynamics, which depend on what a structure allows at each particular moment. The analysis of invariant patterns of reactivity in natural immunoglobulins, inaugurated by Avrameas, expanded by Nóbrega (Nóbrega et al. 1993), and highly refined by Cohen and co-workers (Madi et al. 2011), is highly suggestive of an invariant organization, which, although genetically based (Vasconcellos et al. 1998), is determined epigenetically at each moment. If lymphocytes and immunoglobulins are ceaselessly changing, the maintenance of invariant profiles of reactivity is a strong argument for an invariant organization, which is also assembled in “antigen-free” organisms.
Computer models of the network
The description of maintenance as permanence/constancy of immune reactions with sets of autologous proteins (Cohen’s homunculus) emphasizes the need to define an organization (a “class identity”) for the immune system (Cohen 1992). But this requires a proper definition of terms such as (variable) “structure” and (invariant) “organization.” Cohen’s choice hides this otherwise major advance by using a patchwork of representationist terms, such as homuncular notions, and connectionist terms, such as “information” and “emergence.” He also sees the immune system as a cognitive en-
The possibility to analyze and interpret “global” data, however, depends on the kind of questions being asked. These methods are as good as the theory behind them. Working in Coutinho’s laboratory, Stewart and Varela produced quite a few papers on simulations of network behavior, mainly based on reactions in a set of newborn and adult non-immunized mice monoclonal globulins. They proposed mechanisms of “tolerance” based on internal connectivity and showed that autoimmune diseases are associated with changed patterns of connectivity.
http://www.univie.ac.at/constructivism/journal/6/3/334.vaz
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