Reflex structure and function. (A) The baroreflex is a well-characterized reflex that maintains blood pressure. Like other reflexes, its anatomy consists of a sensory branch coupled with a motor output. The sensory component includes baroreceptors within the aortic arch and carotid sinus, which send information about blood pressure to the central nervous system via the glossopharyngeal (CN IX) and vagus nerves (CN X), respectively. Hypertension activates the reflex leading to cholinergic activation and adrenergic inhibition. This manifests as decreased heart rate and peripheral resistance and ultimately decreased blood pressure. Hypotension has the opposite effect and thereby increases blood pressure. (B) The inflammatory reflex similarly contains sensory and motor branches. In this case, vagus nerve sensory afferents are activated by the products of inflammatory and infectious stimuli. This information is conveyed to the brainstem. After integration by the central nervous system, the reflex is completed by sending vagus motor signals to the celiac ganglion where the splenic nerve arises. (C) The splenic nerve terminates in close proximity to a specialized acetylcholine-producing T cell in the spleen. This T cell behaves similarly to an interneuron: norepinephrine (NE) released by the splenic nerve activates β2 adrenergic receptors (β2ARs) on the T cell, which in turn releases acetylcholine (ACh). The ACh engages the α7 nicotinic acetylcholine receptor (α7nAChR) on splenic macrophages and down-regulates their production of tumor necrosis factor (TNF) resulting in an antiinflammatory effect. The intracellular mechanism for α7nAChR-mediated regulation of cytokine production in immune cells may involve Janus Kinase (Jak) 2 and signal transducer and activator of transcription (STAT) 3 signaling. Pharmacologic α7nAChR agonists (yellow circles) that activate the inflammatory reflex are being developed as potential antiinflammatory therapies. CN = cranial nerve; IL-1β = interleukin-1β.