Pulmonary disease often results from a failure of the many defence mechanisms that usually protect the lung in a healthy individual. These can be divided into physical and physiological mechanisms and humoral and cellular mechanisms.
Physical and physiological mechanisms
HUMIDIFICATION-prevents dehydration of the epithelium. PARTICLE REMOVAL-over 90% of particles greater than 10 J.Lm in diameter are removed in the nostril or nasopharynx. Of the remainder, 5-10 J.Lm particles become impacted in the carina and 1-2 J.Lm particles are deposited in the distal lungs. Most pollen grain (>20 J.Lm) particles are deposited in the nose and conjunctiva.
PARTICLE EXPULSION-by coughing, sneezing or gagging.
RESPIRATORY TRACT SECRETIONS.
The mucus of the respiratory tract is a gelatinous substance consisting chiefly of acid and neutral polysaccharides. The mucus consists of a 5 J.Lm thick gel that is relatively impermeable to water. This floats on a liquid or sol layer that is present around the cilia of the epithelial cells. The gel layer is secreted from goblet cells and mucous glands as distinct globules that coalesce increasingly in the central airways to form a more or less continuous mucus blanket. Under normal conditions the tips of the cilia are in contact with the undersurface of the gel phase and coordinate their movement to push the mucus blanket upwards. Whilst it may only take 30-60 min for mucus to be cleared from the large bronchi, there may be a delay of several days before clearance is achieved from respiratory bronchioles. One of the major long-term effects of cigarette smoking is a reduction in mucociliary transport. This contributes to recurrent infection and in the larger airways it prolongs contact with carcinogens. Congenital defects in mucociliary transport occur. In the ‘immotile cilia’ syndrome there is an absence of the dynein arms in the cilia themselves, and in cystic fibrosis an abnormal mucus is associated with ciliary dyskinesia. Both diseases are characterized by recurrent infections and eventually with the development of bronchiectasis.
Humoral and cellular mechanisms
Non-specific soluble factors
ai-ANTITRYPSIN is present in lung secretions. It inhibits chymotrypsin and trypsin and neutralizes proteases and elastase.
LYSOZYME is an enzyme found in granulocytes that has bacteriocidal properties.
LACTOFERRIN is synthesized from epithelial cells and neutrophil granulocytes and has bacteriocidal properties.
INTERFERON (see p. 139) is produced by most cells in response to viral infection. It is a potent suppressor of lymphocyte function and lowers the threshold for mast cell histamine release. It renders other cells resistant to infection by any other virus.
COMPLEMENT is present in secretions. In association with antibodies, it plays an important cytotoxic role. Pulmonary alveolar macrophages
These are derived from precursors in the bone marrow and migrate to the lungs via the bloodstream. They phagocytose particles, including bacteria, and are removed by the mucociliary escalator, lymphatics and bloodstream. They are the dominant cell in the airways and at the level of the alveoli and comprise 90% of all cells obtained by bronchoalveolar lavage. Macrophages (see p. 133) process antigens and playa part in both cellular and humoral immunity.
The bronchus-associated lymphoid tissue (BALT) consistsof lymphocytes present either in aggregates (tonsils and adenoids) or scattered. It forms an important immunological defence mechanism. Lymphocytes become sensitized to antigens, resulting in local production of secretory IgA. IgG and IgE are also present in secretions derived from B lymphocytes in the lamina propria.