An "eye" in the gut: the appendix as a sentinel sensory organ of the immune intelligence network.

Neural systems are the traditional model of intelligence. Their complex interconnected network of wired neurons acquires, processes, and responds to environmental cues. We propose that the immune system is a parallel system of intelligence in which the gut, including the appendix, plays a prominent role in data acquisition. The immune system is essentially a virtual unwired network of interacting cells that acquires, processes, and responds to environmental data. The data is typically acquired by antigen-presenting cells (APCs) that gather antigenic information from the environment. The APCs chemically digest large antigens and deconstruct them into smaller data packets for sampling by other cells. The gut performs the same function on a larger scale. Morsels of environmental content that enter the gut are sequentially deconstructed by physical and chemical digestion. In addition to providing nutrients, the componentized contents offer environmental data to APCs in mucosa-associated lymphoid tissues (MALT) that relay the sampled information to the immune intelligence network. In this framework, positioning of the appendix immediately after the ileocecal valve is strategic: it is ideally positioned to sample environmental data in its maximally deconstructed state after small bowel digestion. For single-celled organisms, digestion of the environment has been the primary way to sample the surroundings. Prior to the emergence of complex sensory systems such as the eye, even multi-cellular organisms may have relied heavily on digestion to acquire environmental information. While the relative value of immune intelligence has diminished since the emergence of neural intelligence, organisms still use information from both systems in integrated fashion to respond appropriately to ecologic opportunities and challenges. Appendicitis may represent a momentary maladaptation in the evolutionary transition of sensory leadership from the gut to the eye. Relationships between immune dysfunctions and cognition are explored. Copyright 2004 Elsevier Ltd.