22.1 Anatomy and Normal Microbiota of the Respiratory Tract

Anatomy and Microbiota of the Respiratory Tract

The respiratory tract does two jobs at once: it moves air in and out for gas exchange, and it defends the body against the constant stream of microbes carried in with every breath. Understanding the anatomy, the normal microbial residents, and the defense mechanisms of this system gives you the foundation for everything else in this unit on respiratory infections.

Anatomical Structures of the Respiratory Tract

The respiratory tract is divided into upper and lower regions, and the boundary between them matters clinically because infections in each region behave differently.

Upper respiratory tract includes the nasal cavity, pharynx, and larynx.

• The nasal cavity has two functional zones. The anterior nasal vestibule is lined with skin-like epithelium and coarse hairs that filter large particles. The posterior respiratory region is lined with ciliated pseudostratified columnar epithelium and mucus-secreting goblet cells, which together form the first line of defense against inhaled microbes.
• The pharynx is divided into three regions: the nasopharynx (behind the nasal cavity), the oropharynx (behind the oral cavity), and the laryngopharynx (which connects to both the esophagus and the larynx). Each region has its own microbial community.
• The larynx houses the vocal cords and the epiglottis, a flap of cartilage that folds over the airway during swallowing to prevent food or liquid from entering the lower respiratory tract.

Lower respiratory tract includes the trachea, bronchi, bronchioles, and alveoli.

• The trachea is a cartilage-reinforced tube that splits (bifurcates) into the right and left primary bronchi.
• Bronchi branch into progressively smaller secondary and tertiary bronchi, then into bronchioles. Terminal bronchioles are the smallest airways that lack alveoli, while respiratory bronchioles have alveoli budding from their walls.
• Alveoli are tiny, thin-walled air sacs clustered into alveolar sacs. This is where gas exchange happens: oxygen diffuses into the blood and carbon dioxide diffuses out. Pulmonary surfactant, a lipid-protein mixture produced by type II alveolar cells, reduces surface tension and prevents alveoli from collapsing during exhalation.

Microbiota in Respiratory Regions

Different parts of the respiratory tract support different microbial communities, largely because of differences in temperature, moisture, oxygen levels, and nutrient availability.

• The nasal cavity harbors skin-associated bacteria: Staphylococcus spp. (including S. aureus and S. epidermidis), Corynebacterium spp., and Cutibacterium acnes (formerly Propionibacterium acnes).
• The nasopharynx is home to several species that are normal residents in healthy people but can become pathogenic under the right conditions. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis all colonize this region and are common causes of otitis media (middle ear infections) and sinusitis when they spread to normally sterile sites.
• The oropharynx has the most diverse microbiota in the upper tract, including Streptococcus spp. (S. salivarius, S. mitis), Neisseria spp., and the yeast Candida albicans.
• The lower respiratory tract was traditionally considered sterile, but molecular techniques (like 16S rRNA sequencing) have revealed a low-density lung microbiome. Predominant genera include Prevotella, Veillonella, and Streptococcus. The composition of this microbiome shifts in diseases like COPD, asthma, and cystic fibrosis.

Respiratory Tract Defense Mechanisms

The respiratory tract uses layered defenses to keep microbes from reaching the delicate alveolar tissue.

Mechanical defenses:

1. Mucociliary escalator: Goblet cells and submucosal glands secrete mucus that traps inhaled particles and microbes. Cilia on the epithelial surface beat in coordinated waves, sweeping the mucus upward toward the pharynx where it's swallowed or coughed out.
2. Epiglottic reflex: Closes off the airway during swallowing and vomiting, preventing aspiration of microbe-laden material into the lower tract.
3. Cough and sneeze reflexes: Forcefully expel particles and mucus from the airways.

Innate immune defenses:

• Antimicrobial peptides (especially defensins) in respiratory secretions directly kill or inhibit microbes.
• Alveolar macrophages are the resident phagocytes of the lung. They patrol the alveolar surfaces and engulf microbes that make it past the upper defenses.
• Neutrophils are recruited to the site during inflammation and provide additional phagocytic killing power.
• Innate lymphoid cells contribute to mucosal immunity by producing cytokines and helping with tissue repair.

Adaptive immune defenses:

• Secretory IgA antibodies coat mucosal surfaces and neutralize microbes and toxins before they can attach to epithelial cells.
• T cells and B cells mount specific immune responses against pathogens that breach the innate defenses.

The respiratory epithelium itself acts as both a physical barrier and an active participant in defense, producing mucus, antimicrobial peptides, and inflammatory signaling molecules (cytokines and chemokines).

Pathogen Bypass of Respiratory Defenses

Successful respiratory pathogens have evolved specific strategies to get past these defenses:

• Adhesion: Using adhesins or pili to bind tightly to respiratory epithelial cells, resisting the sweeping action of the mucociliary escalator.
• Toxin production: Some pathogens secrete toxins that damage epithelial cells or paralyze cilia. Bordetella pertussis (whooping cough), for example, produces tracheal cytotoxin that destroys ciliated cells.
• Phagocytosis resistance: Capsules (like the polysaccharide capsule of S. pneumoniae) help bacteria resist engulfment by alveolar macrophages. Some pathogens can even survive inside macrophages after being phagocytosed, as Mycobacterium tuberculosis does.
• Antigenic variation: Changing surface proteins to evade recognition by antibodies, which is why influenza virus requires a new vaccine formulation each year.

Microbe–Respiratory System Interactions

Beneficial interactions:

• Normal microbiota compete with potential pathogens for nutrients and attachment sites on the epithelium. This colonization resistance is one of the most important functions of a healthy microbiome.
• Commensal microbes help train and regulate the respiratory immune system. Without this microbial stimulation, immune responses can become either too weak or inappropriately strong.

Pathogenic interactions:

• Viral: Rhinoviruses cause the common cold (upper respiratory). Influenza viruses infect both upper and lower tracts. Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infections in infants and young children.
• Bacterial: S. pneumoniae is the most common cause of community-acquired bacterial pneumonia. M. tuberculosis causes tuberculosis. B. pertussis causes whooping cough.
• Fungal: Aspergillus fumigatus causes aspergillosis and Pneumocystis jirovecii causes pneumocystis pneumonia, both primarily in immunocompromised patients.

Microbiome dysbiosis and chronic disease:

Shifts in the lung microbiome are associated with several chronic respiratory conditions:

• COPD patients show increased Haemophilus spp. and decreased overall microbial diversity.
• Asthma patients tend to have increased Proteobacteria and decreased Bacteroidetes.
• Cystic fibrosis lungs become chronically colonized by antibiotic-resistant Pseudomonas aeruginosa and other opportunistic pathogens, which drives progressive lung damage.