Pulmonary defense mechanisms against pneumonia and sepsis

Abstract

Pneumonia and sepsis are major causes of morbidity and mortality. Lung defense against pathogens involves innate and acquired immune responses. In this review, we focus on lung pathogens associated with sepsis and the innate immune response to them. In addition to discussing typical lung pathogens, the structural defenses, antimicrobial particles, complement, and cellular components of the immune response against these pathogens are also explored. The rising importance of pathogen-associated molecular pattern recognition molecules (such as Toll-like receptors) is discussed, as is the pivotal role of the dendritic cell in linking the innate and adaptive immune response. Although the adaptive response is delayed, it is more specific than the innate response and confers long-lasting memory allowing rapid and efficient clearance of pathogens on subsequent re-exposure. Sepsis interferes with both the innate and adaptive immune responses by inducing marked apoptosis of dendritic cells and lymphocytes, suppressing both arms of the immune response. This immunosuppression is a major hallmark of this disorder. Clearly, understanding the immune response in the lung is critical to the development of future therapeutics for pneumonia and sepsis. This review concludes with novel discoveries in the lung immune response, which may lead to future avenues of treatment.