The lung receives a continual flow of foreign infectious and noninfectious antigens during respiration. Like the gut, genitourinary tract, and skin the lung is one of the interfaces of the sterile body with the environment. The lung's immune defense system and inflammatory mechanisms are poised to deal with this role. In this chapter we will consider the inflammatory and immune roles of two key cells of hematopoietic origin: the lung lymphocyte and the lung macrophage.
While these two cell types interact extensively and might even be considered co-dependent in many situations, they represent two very different arms of the inflammatory response. The macrophage, as a phagocytic cell, is of ancient phylogenetic lineage. It is a sentinel of the innate immune system. As such, it is not antigen specific but it is triggered by many inflammatory stimuli through both specific and pattern recognition receptors. Lymphocytes are present only in vertebrates and represent a significant refinement in the inflammatory response by the ability to recognize and adapt to specific antigens and discriminate between self and nonself. The functional distinction between these two arms of the immune system is blurring with the recent discovery of innate lymphoid-derived immune cells and the appreciation of multiple functions of macrophages in the inflammatory response.
Macrophages or dendritic cells (DCs) are required for optimal presentation of antigens to lymphocytes, and for optimal lymphocyte activation and cytokine production. Conversely macrophage microbicidal function and release of arachidonate and oxygen metabolites is influenced by cytokines produced by activated T lymphocytes and phagocytosis is markedly enhanced by antibodies produced by B lymphocytes. The cooperation between these two cell types represents a cornerstone of lung defense against noninfectious antigen challenge or microbial infection. Another chapter will deal with acute lung inflammation mediated by neutrophilic leukocytes. In this chapter we will present a brief overview of the macrophage and lymphocytes in the human lung, their function and interactions, and a synthesis of their role in lung inflammation and disease.
We will assume a basic knowledge of immunology. However, an explanation of the terminology used in this chapter is appropriate. Many surface receptors expressed by immunologic cells have had multiple names based on different functions. In the past 30 years these terms have been grouped together in a series of standardized “clusters of differentiation” (CD) for the purpose of standard nomenclature. A list of the CD markers referred to in this chapter, other names used for them, and their putative functions are included in Table 21-1.
Table 21-1Cluster of Differentiation Antigens and Surface Molecules Discussed in this Chapter ||Download (.pdf) Table 21-1Cluster of Differentiation Antigens and Surface Molecules Discussed in this Chapter
|Name/CD Designation ||Function |
|CD1 ||Accessory molecule for antigen presentation on APCs |
|Sheep RBC receptor/CD2 ||Accessory molecule for T lymphocyte activation, adhesion receptor (ligand LFA-3) |
|CD3 ||Signaling subunit of TCR |