Editorial T Cells and Blood Vessels

Remarkable advances in our understanding of innate and adaptive immunity have shed light on why inflammation is centrally involved in the pathogenesis of many diseases traditionally not viewed as primarily inflammatory in nature. One key area of progress has been the discovery and study of innate immune receptors, referred to as pattern recognition receptors (PRRs), such as toll-like receptors and nod-like receptors. PRRs recognize molecules commonly produced by microbial pathogens, broadly defined as pathogen associated molecular patterns (PAMPs), but PRRs also recognize self molecules that are indicators of cell injury or death. These self molecules, called damage-associated molecular patterns (DAMPs), include reactive oxygen species, intracellular crystalline deposits, normal molecules in abnormal locations (ATP, heat shock proteins, nuclear proteins), and many others.1,2 DAMPs may be induced or change location because of cell injury or death by any number of causes (genetic, traumatic, toxic, metabolic), and their recognition by innate immune system receptors will initiate responses that include local and systemic inflammation. This is why diseases with just about any underlying cause may be expected to have an inflammatory component. Importantly, the innate immune system has evolved to amplify and modify responses to best combat diverse infections, but these amplified and specialized responses, if inappropriately targeted against self, may themselves become intrinsic to the progression of disease processes. One way this can occur is by innate immune stimulation of adaptive immune responses mediated by T lymphocytes. In fact, normal protective T cell-mediated immunity requires a kick-start by the innate immune system, a condition that ensures that we do not readily mount powerful and potentially harmful adaptive immune responses when there is no real damage or danger present.