Perspectives On Origins Of Natural Immunity And Relation To The Neuroendocrine System

Interest in the dual functional and morphological division of the immune system is pervasive. Clearly access to the totality of immune capability is now balanced with all animals being considered. We now have innate, natural, non-specific, non-anticipatory, non-clonal responses of invertebrates in contrast to the adaptive, induced, specific, anticipatory, clonal responses typical of vertebrates. The innate is considered the most primitive and found in both animal groups; invertebrates do not possess the adaptive system. This duality is expressed at every level of biological organization: molecules, cells, tissues, organs, and organisms. Monolithic immunology, 19lh century preoccupation with humoral mechanisms was split when Metchnikoff discovered phagocytosis in invertebrates. This discovery changed the face of immunology, creating a permanent schism and according equal importance to cellular effectors (leukocytes) obviously the sources of the molecular products that they synthesize and secrete (mediators), the mainstay of the humoral system. Now almost 100 years later, this essential cellular component, and the animal models from which it was derived are, once again, at the center of immunology. However, prevailing taxonomies are changing depending upon the amount and kind of molecular data that emerges. In fact, with discoveries of innate immunity and the Toll pathway, we witnessed a convergence of similar mechanisms between mammals, plants and invertebrates. Thus the strict lines of apparent separation are not at all blurred but are now in sharper focus revealing a pervasive uniformity.

Until technology is refined for the use of relevant invertebrate cells and their specific antibodies, the search for cell differentiation (CD) markers using reagents from mammals will rest as a plausible approach that edges us nearer to a better understanding of origins and possible homologies. With respect to cytokines, where must we go? Further proof and confirmation of the existing linkages invertebrate and vertebrate molecules will do more to explain the whole organism. Clearly we need to resolve relationships by performing more intense genetic analyses. Complement on the other hand is another matter with respect to the immune system where there is greater clarity. The complement cascades in higher vertebrates appear to have evolved from a few primordial genes through gene duplication and subsequent divergence of function. This view is based on similarities in protein sequence and function with complement protein families, the clustered organization of some complement genes, and parallels in organization and function of the lectin, alternative and classical pathways.

The most unique characteristics of natural immunity concern the relation with the immune and connection with the nervous and endocrine systems. This is an example of how linkages exist in the whole organism by means of the three regulatory systems. The stress response comprises a series of coordinated physiological neuroendocrine responses increasing an organism's capacity to maintain homeostasis in the presence of threatening agents. Stress involves hormonal signaling in order to rapidly modulate strategic physiological functions in vertebrates but this kind of more precise evidence for invertebrates is just beginning to emerge. What still needs to be resolved is the precise appearance of pro-opiomelanocortin-derived peptides (e.g., ACTH), as a unifying theme in the neuroendocrineimmune system and to eventually link this in more clearly with those characteristics that are closer to immune than those associated with the neuroendocrine system, [62-64],

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