Codes of Complexity

What general conclusions may we draw from the analysis so far? The first conclusion is that the immune self is not a platonic, autonomous, and monolithic entity that corresponds through rigid rules to a certain molecular entity, but a context-dependent construct. There is no Self with a capital S. In other words, the question of what is self or nonself cannot be answered by reference to a specific entity. Being self or nonself depends on the response of the immune system in a given context, and this context, although governed by regularity (e.g. the context of infection), is always a local one, as Volosinov suggests.

If we adopt this perspective, then the self turns out to be a highly contextual and fuzzy concept that is actively inferred from raw data rather than passively conferred by our genes. This perspective can be illustrated by tolerance of sperm in the testes and tolerance of malignant tumors.

The components of a context suggested by Volosinov may be easily applied to the case of the testes. The spatial purview shared by the agents is the totality of biological objects in the local functional organ or complex. Spermatozoa in the testes are in an immunologically legitimate spatial position. The common knowledge and understanding of the circumstances - the result of years of being involved in patterns of interactions - is the established pattern of relations between the objects. It is a biological convention and a regularity (or habit, to use Peirce's term) among male mammals for sperm cells to be produced in the testes. Transferring sperm cells to another biological site would be a violation of this habit/regularity and would elicit a response. Finally, the "common evaluation of these circumstances" is produced by the immunological agents' complex process of communicating with and responding to each other. Hormones that signal the production of sperm cells and macrophages that sense the state of a tissue are just a few of the agents that provide input for evaluating the circumstances. When one gets a kick in the groin, sperm antibodies might be produced because the evaluation of the circumstances has changed.

The idea that the system's response to a given entity is what defines the meaning of the entity is not new either in semiotics (Volosinov, 1986) or in immunology (Cohen, 2000a,b). A genuine contextualist always insists that meaning is encapsulated not in the message, which is in itself devoid of meaning, but in the response to the message. In this context the immune system is no exception; immune tolerance in the testes is just a concrete example of this logic.

What is the major implication of considering the immune self to be a contextual construct? Identifying the objects involved in the immune response is a relatively easy task that has been carried out successfully. However, mapping the relations between this polyphony of agents is a demanding and complex task, and understanding the correspondence between the objects involved in the immune response and the abstract, dynamic pattern of relations that organize their behavior is currently beyond our grasp. As the late Ray Paton (2002, p. 63) argued, "From a biological system's point-of-view there is a lack of tools of thought for dealing with integrative issues [such as this]." However, we are now in a better position to understand the immune self. We realize that the meaning of the immune self, like the meaning of any other sign, is inferred from the system's response to a given signal and is not encapsulated in the signal itself. There is no positive definition of the immune self as the genetic-reductionist approach says there is; there is no negative definition of the self as Burnet would have it; and there is no postmodernist hall of mirrors with which the immune system narcissistically occupies itself. The immune self is defined post hoc as those objects to which the system responds with tolerance. It is defined in terms of the system's response as revealed by the semiotic equivalent of a contextual analysis.

How can a simple convention of correspondence turn into a complex coding system? How is it that as children we learn that the word "cat" corresponds to the feline mammal and as adults we understand it as a context-dependent sign that can correspond, for example, to a jazz player? We are still far from answering this question. Identifying the dynamics that turn simple rules of correspondence into complex patterns of meaning is a challenge facing those interested in living systems. Inquiring into the complexity of codes may provide us with insight into immune memory (Neuman, 2007), the irreducibility of biological systems (Neuman, 2005b), the mystery of cryptobiosis (Neuman, 2006), and many other biological phenomena that the current paradigm fails to address.

Acknowledgements A previous version of this manuscript was published in S.E.E.D. Journal. I would Like to thank Irun Cohen and Peter Harries-Jones for their constructive comments and support and Marcello Barbieri for his editorial assistance.

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