MECHANISMS OF DISEASE Immunologic Aspects of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The importance of the inflammatory component in COPD is highlighted in the definition, inviting to a broader look at the possible involvement of the immune system in the pathogenetic events of COPD. The implication of an inflammatory response to the pathogenesis of emphysema is not new, but our knowledge of the mechanisms regulating the activation and persistence of this response in the lung is continuously evolving. Starting from the hypothesis of elastase-antielastase imbalance, proposed more than 40 years ago, studies first focused on the role of neutrophils and macrophages, and their ability to induce lung destruction through the release of proteolytic enzymes. However, activation of neutrophils and macrophages by itself is not sufficient to explain all the pathogenetic traits of COPD and more recent evidences suggest a crucial role for acquired immunity, with involvement of dendritic cells and lymphocytes. This hypothesis was based on the observation that B and T lymphocytes, especially of the CD8+ subset, were the predominant cells infiltrating lung tissue of patients with COPD and their numbers were strongly related to the apoptosis of structural cells and lung function impairment. It has been recently proposed that this adaptive immune response, at least in some patients, could have an autoimmune component due to the recognition of pulmonary self-antigens modified by cigarette smoking and to the failure of mechanisms regulating immunological tolerance. In an organ as the lung, incessantly exposed to the air, the contribution of cells of the immune system is essential to sense inhaled antigens, either inducing tolerance to inoffensive substances, or initiating immunity against a potential harmful pathogen. This immunological homeostasis requires stringent control mechanisms to protect the vital and fragile gaseous exchange barrier from unrestrained inflammation that, instead of defending it, can cause significant damage.