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© 2007 The American Thoracic Society
doi: 10.1513/pats.200701-002FM
The Immunopathogenesis of Chronic Obstructive Pulmonary Disease
Insights from Recent Research
1 Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Health System, Ann Arbor, Michigan; 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and 3 Graduate Program in Immunology, University of Michigan Health System, Ann Arbor, Michigan; and 4 University of British Columbia, Centre for Cardiovascular and Pulmonary Research, and 5 St. Paul's Hospital, Vancouver, British Columbia, Canada
Correspondence and requests for reprints should be addressed to Jeffrey L. Curtis, M.D., Pulmonary and Critical Care Medicine Section (506/111G), Department of Veterans Affairs Medical Center, 2215 Fuller Road, Ann Arbor, MI 48105-2303. E-mail: jlcurtis{at}umich.edu
ABSTRACT
Chronic obstructive pulmonary disease (COPD) progression is characterized by accumulation of inflammatory mucous exudates in the lumens of small airways, and thickening of their walls, which become infiltrated by innate and adaptive inflammatory immune cells. Infiltration of the airways by polymorphonuclear and mononuclear phagocytes and CD4 T cells increases with COPD stage, but the cumulative volume of the infiltrate does not change. By contrast, B cells and CD8 T cells increase in both the extent of their distribution and in accumulated volume, with organization into lymphoid follicles. This chronic lung inflammation is also associated with a tissue repair and remodeling process that determines the ultimate pathologic phenotype of COPD. Why these pathologic abnormalities progress in susceptible individuals, even after removal of the original noxious stimuli, remains mysterious. However, important clues are emerging from analysis of pathologic samples from patients with COPD and from recent discoveries in basic immunology. We consider the following relevant information: normal limitations on the innate immune system's ability to generate adaptive pulmonary immune responses and how they might be overcome by tobacco smoke exposure; the possible contribution of autoimmunity to COPD pathogenesis; and the potential roles of ongoing lymphocyte recruitment versus in situ proliferation, of persistently activated resident lung T cells, and of the newly described T helper 17 (Th17) phenotype. We propose that the severity and course of acute exacerbations of COPD reflects the success of the adaptive immune response in appropriately modulating the innate response to pathogen-related molecular patterns ("the Goldilocks hypothesis").
Key Words: adaptive immunity • adhesion molecules • chemokines • cytokines • innate immunity
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