Cory M. Hogaboam

The Role of Chemokines in Linking Innate and Adaptive Immunity

Of the myriad of immune defense systems that exist in nature, the mammalian defense system is clearly the most sophisticated and successful. This immune sophistication arises from the fact that immune events in mammals involve a progression of detailed events leading to exquisite specificity toward a bacterial, viral, or fungal byproduct, or a nonself protein. On its simplest level, the immune response in mammals is divided into two major components: the nonspecific innate and the adaptive or acquired immune systems (1). When examined phylogenetically, the innate immune system appears to be more ancient than its acquired counterpart, and, historically, it was thought that the innate response was nonselectively directed toward microorganisms. However, the distinctions between the innate and acquired immune responses are now widely viewed as somewhat artificial, as it has been shown that both arms of the immune response share several common features including amazing degrees of specificity for pathogens and foreign antigens (2). Indeed, there is increasing evidence that the induction of different types of effector adaptive responses is directed by the innate immune system after its highly selective recognition of particular groups of pathogens through pattern recognition molecules (i.e., the Toll-like receptor family) and the elaboration of soluble protein signals that activate the relevant lymphoid cell population.

The Role of CC Chemokines in Th1- and Th2-Type Pulmonary Inflammation Models

Elucidation of the factors involved in the initiation and persistence of inflammatory diseases within the interstitial space of the lung has garnered great research interest over the past two decades. Interstitial lung diseases are defined as pulmonary inflammatory disorders that lead to excessive tissue injury and progressive fibrosis. Idiopathic fibrosis and end-stage sarcoidosis are two clinically predominant examples (1). Whereas the list of inflammatory mediators present in interstitial lung diseases has grown immensely to include cytokines, growth factors, prostanoids, eicosanoids, and free radicals (2) little is presently known about the manner in which these factors initiate and sustain these complex diseases. An inflammatory response to infection or injury within the lung is typically characterized by the de novo generation of inflammatory mediators by tissue resident immune (i.e., alveolar macrophages and mast cells) and nonimmune (i.e., epithelial) cells. These mediators modulate the function of these cells and also promote the infiltration of lymphocytes and phagocytes, and the concerted efforts of all of these cells facilitate the destruction and/or clearance of the inflammatory stimulus. Once this aim has been achieved, the last stage of the inflammatory response involves the restoration of the tissue to its original state. Clearly, the recruitment and tissue-reparative stages must be closely regulated in the lung because excessive tissue injury or overexuberant tissue healing can significantly disrupt the pulmonary architecture and even lead to respiratory failure (3). In prolonged inflammatory diseases of the lung, clinical and laboratory evidence suggest that the inability of the lung to contain the inflammatory process and/or repair itself correctly is related to the persistence of one or several inflammatory signals (4).