Biology of Cognition
The Specificity of Immunologic Observations Nelson M. Vaz
description, which are typical of the context established by Maturana in his biology of cognition and language is also minimized in Varela’s work. Describing a cognitive immune system is quite different from claiming that the immunologist arbitrates which phenomena are specific and which are not, tracing a boundary between antibodies and unspecific immunoglobulins, as Jerne and Talmage did in the past. As a consequence, descriptions of immunological activities based on Varela’s ideas and descriptions based on Maturana’s ideas may be significantly different.
The case of “oral tolerance” With the emergence of the clonal selection theory, the idea of a spontaneous immunoglobulin production preceding the encounter with antigens – which was Jerne’s main idea – vanished from sight. The fundamental tenet of Jerne/Talmage’s theories was replaced with a collection of lymphocyte clones, previously purged of self-reacting forbidden clones, waiting for possible activation (clonal expansion in specific immune responses) upon exposure to antigens to which they bind – and which might never appear. Also gone was the possibility to suggesting anything about the organism’s construction. Unstimulated organisms, therefore, would remain immunologically idle. There is no such a thing as a non-stimulated organism. Change is an essential condition of living (Mpodozis 2011). Organisms change immunologically by the simple act of eating proteins produced by other organisms, and also by existing in contact with an abundant commensal microbioma: they become “orally-tolerant” to these materials (Vaz et al. 1997). If subsequently exposed to these materials under otherwise immunogenic conditions, i.e., with adjuvants and by parenteral routes, they react much less than animals that did not contact them by the digestive route. However, what is presently called “oral tolerance” is nether immunization nor the development of tolerance (ignorance, neglect) to these materials. No form of “tolerance” is absolute. Animals submitted to treatments that result in “oral tolerance” still
form specific antibodies upon subsequent (parenteral) immunization, in magnitudes that are inversely proportional to the ingested (tolerizing) dose of the antigen. But these partially inhibited “immune responses” differ drastically from those resulting from parenteral immunization because they display no “memory”: they are not progressive; the levels of antibody formed are robustly stable even in face of repeated parenteral immunizations with adjuvant (Verdolin et al. 2001). A similar situation is present in the formation of “auto-antibodies” and the activation of “self-reacting” lymphocytes. There is a physiological “auto-reactivity.” Self/nonself-discrimination is a pseudo-problem. The real question is the robust, although dynamic, stability of immunological activity. We must define the organization of immunological activities, and contact with dietary materials is an excellent way to examine this problem.
Attempts to alter robust stable equllibria In a long trend of work, Carvalho and co-workers have shown that the exposure of “orally-tolerant” animals to “tolerated” antigens under otherwise immunogenic conditions inhibits the initiation of a variety of other immunological phenomena (Carvalho, Verdolin & Vaz 1996). It may alter the organization of granulomas (Carvalho et al. 2002), the pattern of healing of skin wounds (Costa et al. 2011), and inflammation resulting from the injection of carrageenan (Ramos et al. 2008). Thus attempts to interfere with the immunological status quo may trigger potent anti-inflammatory mechanisms. Furthermore, the immunological status quo of body components in the adult organism is not fixed, as proposed by the hypotheses of “self-tolerance.” Not only may it possibly break down as in “autoimmune” diseases, but, as shown by Ramos (2011a), it can be reinforced by artificial toleranceinducing protocols. Rats orally pretreated with an extract of rat heart, are less damaged by injection of super-high doses of isoproterenol, which triggers lesions similar to myocardium infarction (Ramos 2011b).
A large degree of redundancy The lymphoid system maintains an intense rate of replacement of cellular and molecular components, and yet maintains invariance in many parameters – such specific immunity and tolerance – with lifelong duration at times. This ceaseless replacement of components creates a situation that is almost the opposite of what is commonly imagined to happen in specific immunization. Different children immunized with the same vaccine are imagined to form the same protective antibodies, but the antibodies, although equivalent, are never the same. Even in the same child they keep changing; they are always being replaced by others. A second example is found in children born with congenital defects that block the production of immunoglobulins, such as in agammaglobulinemia. If diagnosed soon enough, many of these children can live near normal lives if they periodically receive injections of gamma-globulins collected from panels of blood donors. These globulins are not those the child would form by her/himself, but they are equivalent. This equivalence relies on the wide plurality of globulins and also on their “polyspecificity” (Wucherpfennig et al. 2007), which is probably necessary for healthy living.
Pathogenesis by disconnection Somehow, this plurality creates a form of beneficial coalition in the immunoglobulin network. This is further suggested by the association of expansions of lymphocyte populations with a sub-optimal degree of diversity (so-called “oligoclonal expansions”) with many forms of immunopathology, ranging from severe forms of infectious and parasite diseases (Finger et al. 2005; Fesel et al. 2005) to allergic diseases (Davies & O’Hehir 2004), diseases of autoimmune origin (Quintana et al. 2008), and some forms of congenital abnormalities (Leavy 2007). Thus, losing some form of global integration and allowing the expansion of a particular sector of the lymphocyte network may have pathogenic consequences.
http://www.univie.ac.at/constructivism/journal/6/3/334.vaz
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