[Frontiers in Bioscience S5, 575-587, January 1, 2013]

The role of natural killer cells in pulmonary immunosurveillance

Pamela Rose Hesker1, Alexander Sasha Krupnick1

1Department of Surgery and The Alvin Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Ave., St Louis, MO


1. Abstract
2. Introduction: functional and molecular characterization of NK Cells
3. NK Cell Activation
3.1 .Human KIRs and LIRs and their functional counterparts in mice
3.2 .Detection of MHC I and the Licensing Hypothesis
3.3 .Activating receptors bind stress ligands
3.4 .Priming of NK cells
4. Mechanisms of Effector Functions
5. Genetic influences on NK cell function in mice and man
6. Maturation, migration, peripheral seeding, and the influence of the environmental milieu on NK cells
7. The Role of NK cells in pulmonary immunosurveillance
7.1 .Primary Lung Cancer
7.2 .Metastatic cancer to the lung
7.3 .The role of NK cells in pulmonary infection
7.3.1. Viral infections
7.3.2. Bacterial infections
7.3.3. Mycobacterial infection
8. Conclusion and Perspectives
9. References


Natural killer (NK) cells were originally identified as lymphocytes capable of killing cancer cells without prior sensitization (1). Further characterization of these cells in both humans and rodent models has expanded their role towards a broad-based immunosurveillance of diseased and healthy peripheral tissues. Among peripheral organs, the lung contains the largest percentage of NK cells. Accordingly, NK cells are implicated in many immunological responses within the lung, including innate effector functions as well as initiation of the adaptive immune response. In this article, we review the characteristics of NK cells, current models of NK maturation and cell activation, migration of NKs to the lung, and effector functions of NKs in cancer and infection in the airways. Specific emphasis is placed on the functional significance of NKs in cancer immunosurveillance. Therapeutic modulation of NK cells appears to be a challenging but promising approach to limit cancer, inflammation, and infection in the lung.