Fig. 1.

Schematic illustration of the bovine respiratory immune system emphasizing the innate components. Depicted are immune systems within 3 main regions of the respiratory tract: the airways (upper respiratory tract to the bronchi), bronchiole, and alveoli. Airway: Conducting airways are lined by pseudostratified ciliated epithelium that transports the air-surface liquid (ASL) anteriorly toward the pharynx or nares. ASL is produced by secretion products from goblet cells and submucosal glands. Within the ASL are mucins (see text), as well as antimicrobial proteins (eg, lysozyme, lactoferrin, surfactant proteins A and D, SLPI, PLUNC, and others) and antimicrobial peptides (defensins and RNAase 7), which are produced by ciliated epithelial cells. The oxidative defense system (ODS) is composed of lactoperoxidase (LPO) produced by submucosal glands, dual function oxidases 1 and 2 (Duox1 and Duox2) produced by epithelia, and thiocyanate (SCN-) transport proteins produced by epithelia. Duox1 and 2 produce hydrogen peroxide (H₂O₂), which, in the presence of SCN-, is converted to OSCN-, which has potent antimicrobial activity. Bronchioles: Bronchioles are lined by Clara and Type II cells, both of which also produce antimicrobial proteins and peptides. Clara cells also produce CC10, an immunomodulatory protein, and express cytochrome P450 enzymes that biometabolize toxins. With injury, Type II and Clara cells proliferate and replace damaged cells. Alveoli: Type I pneumocytes line the alveolar lumen and are covered by surfactant phospholipids that are admixed with surfactant proteins, antimicrobial proteins, and antimicrobial peptides. With injury, Type I pneumocytes are replaced by Type II cells, which then differentiate into Type I cells. Effector cells: Neutrophils, alveolar and intravascular macrophages, alpha/beta T (CD4 and CD8) cells, and gamma/delta T cells along with B, NK, and dendritic cells are effector cells present along the respiratory tree for induction of adaptive immune responses. With inflammation, neutrophils and macrophages are present in the alveolar lumen, bronchioles, and airways. Other immune responses such as pattern recognition receptors as well as cytokine, interferon, and chemokine responses are not included in this figure.