INFECTIONS OF THE RESPIRATORY SYSTEM
The respiratory system is constantly exposed to inhaled microorganisms but is protected by extensive defenses. The nose filters out particles larger than 10 Lm although those smaller than 5 Lm may reach the bronchi and alveoli. Inaddition, there is a host of immune defenses including alveolar macrophages, secretory IgA antibodies, complement proteins, surfactant proteins, secreted defensins and lactoferrin . Despite this, infections of the respiratory tract are frequent causes of illness. The World Health Organization (WHO) has reported that many hundreds of millions of patients suffer acute infections of the lower respiratory tract worldwide. Figure 3.6 indicates the sites of a number of respiratory diseases.
Respiratory viruses are transmitted directly by aerosols or indirectly from contaminated surfaces. The first site of attack is, not surprisingly, the epithelium of the nose and throat. Indeed, the hundreds of corona and rhinoviruses that cause the common cold replicate at 32 to 33oC, the temperature of the mucosal surface lining the nose. The influenza viruses (Figures 2.4 and 2.8) infect and replicate in respiratory epithelial cells causing cellular damage. The generalized symptoms that present, such as muscular aches, malaise and anorexia, suggest the virus may spread systemically from the respiratory tract but there is no conclusive evidence for this.
The loss of ciliated and mucus producing epithelial cells impairs clearance of invading microbes and creates conditions for secondary bacterial infections of staphylococci, streptococci or Haemophilus influenzae. Bacterial proteases, for example the V8 protease of Staphylococcus aureus, can enhance the infectiveness of the influenza virus by improving virus adhesion.
Corynebacterium diphtheriae (Figure 3.7) and Bordetella pertussis (Figure 3.8) are obligate bacterial pathogens. Corynebacterium diphtheriae infectsthe nasopharynx and the tonsils and may lead to a lethal systemic infection affecting the heart, liver and kidneys. Bordetella pertussis is the causative agent of whooping cough. It adheres to the epithelial cells lining the trachea and bronchi where it interferes with ciliary action and releases toxins and substances that damage and kill cells and irritate the surface, causing the characteristic cough. Effective vaccines are available against both organisms although 40 million infections of whooping cough occur annually worldwide. In contrast, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcusaureus and Moraxella catarrhalis, make up to 60% of the normal bacterialpopulation of the nasopharyngeal mucous membrane in healthy individuals. They can become opportunistic pathogens in immunosuppressed individuals or following changes to the bacterium that render it increasingly virulent. The commonest form of bacterial pneumonia is lobar pneumonia caused by Streptococcus pneumoniae and results in a massive inflammation of one lobe of the lung. Staphylococcus aureus may cause bronchopneumonia, while Haemophilus influenzae can infect the epiglottis.
Mycobacterium tuberculosis (Figure 3.9) causes tuberculosis (TB) of the lungand may be considered a rather special case of bacterial infection of the lower respiratory tract. The bacteria enter the alveoli in inhaled air and are phagocytozed by macrophages where they escape being killed and multiply . Mycobacteria can then enter the lymphatic system and invade a neighboring lymph node. The healing of local lesions leads to calcification of the lung tissues. In immunodeficient individuals, the lymph nodes and tissues may be progressively affected until eventually the mycobacteria are spread by the blood. Also with impaired immunity, dormant Mycobacteriumtuberculosis can be reactivated causing a severe form of pneumonia.
Atypical pneumonias can result from infections with Mycoplasmapneumoniae, Chlamydia pneumoniae and Legionella pneumophila. Theseinfections are associated with ‘flu-like' symptoms, such as high temperatures and coughing, although bronchial secretions and sputum do not contain pus as would be expected of a typical bacterial lobar pneumonia.
Generally, pathogenic fungi do not produce toxins but damage tissues directly or disturb normal metabolic functions and can induce hypersensitivity responses . Fungi can cause respiratory infections; Aspergillus fumigatus can invade the respiratory system and lead to one of several types of diseases. It may simply grow in the mucus of the bronchi and induce a hypersensitive state but may invade old wound cavities of the lungs, such as those resulting from TB, and grow as a solid mass called an aspergilloma. Aspergillosis may also result from an invasive growth in the lungs and other tissues. Generally, the infective dose of spores is extremely large although the invasive form may be secondary to other systemic diseases. Similarly, Pneumocystis carinii can cause a serious pneumonia (PCP) in AIDS compromized patients. The yeast, Candida albicans, is also an opportunistic agent in sufferers of AIDS.