Ten years ago, a group of researchers, led by Francisco Varela, were proposing an alternative vision of the immune system main behavior and function. I was part of this group. This new vision saw the immune system not as behaving distinctively with self and non-self or according to any dichotomy imposed a priori and from outside (the self-recognition vision), but rather as behaving in a unique way. From this indifferent behavior, any external impact would progressively been treated in two different ways, reactive and tolerant, but now, consequently and from inside the system (the self-assertion view). This paper will recall, through a very artificial simulation, the difference existing between these two visions. Also at that time, we believed that, from an engineering perspective, this new vision, emphasizing more the adaptability and the need for endogenous constraints than the recognition and the defensive ability, although less obvious to accept than the classical defensive one, should be more beneficial. These last ten years proved that we haven’t been convincing enough, and in this paper I resume the crusade.

Biology gives us numerous examples of self-assertional systems whose essence does not precede their existence but is rather revealed through it. Immune system is one of them. The fact of behaving in order not only to satisfy external constraints as a pre-fixed set of possible environments and objectives, but also to satisfy internal “viability” constraints justifies a sharper focus. Adaptability, creativity and memory are certainly interesting “side-effects” of such a tendency for self-consistency. However in this paper, we adopted a largely pragmatic attitude attempting to find the best hybridizing between the biological lessons and the engineering needs. The great difficulty, also shared by neural net and GA users, remains the precise localisation of the frontier where the biological reality must give way to a directed design.

The following basic question is studied here: In the relatively stable molecular environment of a vertebrate body, can a dynamic idiotypic immune network develop a natural tolerance to endogenous components? The approach is based on stability analyses and computer simulation using a model that takes into account the dynamics of two agents of the immune system, namely B-lymphocytes and antibodies. The study investigates the behavior of simple immune networks in interaction with an antigen whose concentration is held constant as a function of the symmetry properties of the connectivity matrix of the network. Current idiotypic network models typically become unstable in the presence of this type of antigen. It is shown that idiotypic networks of a particular connectivity show tolerance towards auto-antigen without the need for ad hoc mechanisms that prevent an immune response. These tolerant network structures are characterized by aperiodic behavior in the absence of auto-antigen. When coupled to an auto-antigen, the chaotic attractor degenerates into one of several periodic ones, and at least one of them is stable. The connectivity structure needed for this behavior allows the system to adopt particular dynamic concentration patterns which do not lead to an unbounded immune response. Possible implications for the understanding of autoimmune disease and its treatment are discussed.

This article investigates the following basic question: in the relatively stable molecular environment of a vertebrate body, can a dynamic idiotypic immune network develop a natural tolerance to endogenous components? Our approach is based on stability analysis and computer simulation using a model that takes into account the dynamics of two agents of the immune system, namely, B-lymphocytes and antibodies. We investigate the behavior of simple immune networks in interaction with an Ag whose concentration is being held constant as a function of the connectivity matrix of the network. The latter is characterized by the total number of clones, N, and the number of clones, C, with which each clone interacts. The idiotypic network models typically become unstable in the presence of this type of Ag. We show that idiotypic networks that can be found in particular connected regions of NC-space show tolerance towards auto-Ag without the need for ad hoc mechanisms that prevent an immune response. These tolerant network structures provide dynamical regimes in which the clone which interacts with the auto-Ag is suppressed instead of being excited such that an unbounded immune response does not occur. Possible implications for the future treatment of auto-immune disease such as IvIg-treatment are discussed in the light of these results. Moreover, we propose an experimental approach to verify the results of the present theoretical study.

In this paper we present a new model for the mechanism underlying what is traditionally known in immunology as the “selfnonself” distinction. It turns out that in operational terms, the distinction effected by this model of the immune system is between a sufficiently numerous set of antigens present from the start of the ontogeny of the system on the one hand, and isolated antigens first introduced after the system has reached maturity on the other. The coincidence between this “founder versus late” distinction and the traditional “somatic self-foreign pathogen” one is essentially contingent, an example of the purely opportunistic tinkering characteristic of biological organization in general. We conclude that the so-called “self-nonself” distinction in immunology is a misleading misnomer. This raises the question as to what would genuinely count as a “self-nonself” distinction, a fundamental question for biology in general and Artificial Life in particular.

Open peer commentary on the article “The Epigenetic Immune Network” by Nelson Monteiro Vaz & Luiz Antônio Botelho Andrade. Upshot: Vaz and Andrade recount how Varela collaborated with a group of immunologists to advance a nonconformist view of the immune system. Here, I outline my interpretation of four concepts related to the philosophy of the immune system that Vaz and Andrade associate with the ideas of Varela: modeling, cognition, closure and enaction.

This paper considers current concepts of autoimmunity and concludes with a discussion on the need for viable alternatives. It is argued that, if a century of ‘horror autotoxicus’ and over 30 years of active research based on ‘clonal deletion’ models have failed to contribute solutions to the problem, these notions are probably inadequate. Instead, it is proposed that pathological states of autoimmunity should be considered as deviations from normal autoreactivity which is a central property of the immune system. It follows that the study of autoimmune physiology is necessary to the understanding of pathology. Furthermore, the discrimination between destructive immune responses and physiological, self-directed immune activities is thought to be a systemic property based on a particular network organization, rather than the result of isolated clonal properties. These views suggest novel strategies in basic and clinical approaches to autoimmunity, more particularly the possibility of manipulating physiological autoreactivity to compensate diseases which are not of immunological origin.

Neurophenomenology is a research programme aimed at bridging the explanatory gap between first-person subjective experience and neurophysiological third-person data, through an embodied and enactive approach to the biology of consciousness. The present proposal attempts to further characterize the bodily basis of the mind by adopting a naturalistic view of the phenomenological concept of intentionality as the a priori invariant character of any lived experience. Building on the Kantian definition of transcendentality as “what concerns the a priori formal structures of the subject’s mind” and as a precondition for the very possibility of human knowledge, we will suggest that this transcendental core may in fact be rooted in biology and can be examined within an extension of the theory of autopoiesis. The argument will be first clarified by examining its application to previously proposed elementary autopoietic models, to the bacterium, and to the immune system; it will be then further substantiated and illustrated by examining the mirror-neuron system and the default mode network as biological instances exemplifying the enactive nature of knowledge, and by discussing the phenomenological aspects of selected neurological conditions (neglect, schizophrenia) In this context, the free-energy principle proposed recently by Karl Friston will be briefly introduced as a rigorous, neurally-plausible framework that seems to accomodate optimally these ideas. While our approach is biologically-inspired, we will maintain that lived first-person experience is still critical for a better understanding of brain function, based on our argument that the former and the latter share the same transcendental structure. Finally, the role that disciplined contemplative practices can play to this aim, and an interpretation of the cognitive processes taking place during meditation under this perspective, will be also discussed.

Key words: neurophenomenology, kant, a priori, prereflective awareness, default mode network, ongoing activity, free-energy, meditation.

The immune self is our reified way to describe the processes through which the immune system maintains the differentiated identity of the organism and itself. This is an interpretative process, and to study it in a scientifically constructive way we should merge a long hermeneutical tradition of asking questions about the nature of interpretation together with modern understanding of the immune system, emerging sensing technologies and advanced computational tools for analyzing the sensors’ data. Relevance: The author claims that our immune system is a meaning-making system in the context of biology of cognition as well as the hermeneutical tradition.

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.