CELLS, MOLECULES AND MECHANISMS INVOLVED IN THE NEURO-IMMUNE INTERACTION

Abstract

The existence of a surveillance and protection system against pathogens and malignant cells has evolved until reach, in the most complex organisms, a very sophisticated immune system composed of an innate arm and an adaptive arm. The innate immune system constitutes the first defense barrier against foreign organisms but it comprises relatively poor diversity of antigen (Ag)-specific recognition elements. In contrast, the adaptive immune system shows a delayed response, and involves numerous Ag-specific recognition elements and highly efficient mechanisms both to eliminate foreign pathogens and tumor cells, and to maintain tolerance to self constituents. T cells are the central players in the adaptive immune response. These cells direct and regulate the function of several immune system cells, thus orchestrating efficient elimination of threats and, at the same time, promoting tolerance to healthy self tissues. Growing evidence has shown that some cells from the adaptive immune system, specially the T cell compartment, constitute an important link between the nervous system and the immune system. Due to their pivotal role directing immune responses and tolerance, T cells become strategic target cells to be regulated by the nervous system. On the other hand, evidences point toward T cells not only play an important role driving the elimination of pathogens and tumors and maintaining tolerance to self constituents, but also regulate some nervous system functions such as acquisition of memory and behaviour. This chapter is geared toward analyze and discuss the current knowledge and growing evidences about the interactions between the nervous system and the immune system of the complex organisms. Because mammals present the most complex and sophisticated immune system among the organisms, and most evidences described in the literature correspond to studies of neuro-immune interactions analyzed in these animals, the discussion in this chapter is bounded to mechanisms operating in mammals. The bidirectional interaction between the nervous system and immune system will be analyzed at the level of cellular and molecular mechanisms. In the first half of this chapter, interactions between immune and nervous systems will be analyzed in both directions: the immune system mediated regulation of nervous system and the nervous system mediated regulation of immunity. Both kinds of interactions will be analyzed separately for simplification and better understanding. The second half of this chapter will be geared to analyze how immune cells can communicate between them using neurotransmitters and how nervous system cells can also interact with each other using cytokines. Despite this second part of the chapter does not analyze direct neuro-immune interactions, it contributes to understand how both, nervous system and immune system use the same mediators and receptors, which therefore may participate in regulation of immunity, nervous system regulation and also in neuro-immune interactions.