Respiratory system infections Upper, lower Severity tends to depend on: Where infection is established (and whether it

1. Respiratory system infections Upper, lower Severity tends to depend on: Where infection is established (and whether it spreads) Age and robustness of immune system Virulence factors of organism

2. Respiratory system environment is diverse • Upper respiratory system • Nose, pharynx, associated structures • Purpose: to take in, warm and moisten air • Most common site of infections • Lower respiratory system • Larynx, trachea, bronchi, alveoli • Purpose: ventilation, gas exchange

3. Geography of the respiratory system (and sites of infection)

4. Protective structures of the respiratory system Mucous membranes Hairs; ciliated epithelia Lymphoid tissues (tonsils) “Mucociliary escalator” keeps microbes out of lower respiratory tract Alveolar macrophages; IgA

5. Most of the respiratory system is NOT colonized by normal flora Generally confined to nose, nasopharynx and pharynx

6. Upper respiratory system • Pharyngitis, laryngitis, tonsillitis, etc. • Can be caused by bacteria, viruses or both • Usually self-limiting • S pyogenes is an important pathogen • Resistant to immune system • Produces toxins (superantigens) • Immune reaction (glomerulonephritis, rheumatic fever)

7. Diphtheria disease also caused by exotoxin picked up by some cells but not others inhibits protein synthesis (kills cells) Vaccines have been available for a long time neutralize toxin Passive immunization is available

8. Microbial infections of associated areas Otitis media Conjunctivitis Sinusitis Both bacterial and viral infectious agents have been found (implications for treatment?) Viral infections- rhinitis, pharyngitis, etc. too many types!

9. Lower respiratory infections • Usually stopped by immune/mechanical means • Pneumonia (inflammation of lung) • Tuberculosis (chronic inflammation) • Whooping cough (kills ciliated cells)

10. Many infectious agents cause pneumonia Bacterial Legionella- spreads in ventilation systems Mycoplasma (walking pneumonia) very unusual microbes “Pneumococcus” (S. pneumoniae) • Encapsulated; causes inflammation • Can spread and cause endocarditis, meningitis, septicemia

12. Diagnosis by culture; X-ray Which lung is affected?

13. Tuberculosis • Gram+ bacterium infects macrophages • Hypersensitivity reaction damages lung tissue • Many people are infected; most do not develop TB • Mantoux test detects prior exposure • Aggressive and long-term antibiotic treatment is required

14. Several viral pneumonias also described • Adenovirus • Complications of influenza • Affects many types of animals (wild and domesticated); source of genetic exchange • Can frustrate immune system due to constant antigen change • RSV (respiratory syncytial virus) • Especially dangerous for infants • Tends to recur

15. Mechanisms of viral respiratory infections • Influenza • kills epithelial cells; spreads rapidly to other cells • RSV • Kills epithelial cells which can block respiratory passages

16. Hantavirus pulmonary syndrome • Spread by inhalation of dust contaminated by mice • High fatality rate (40%) • No person-to-person spread • Infects capillary epithelium; blood vessel damage and shock

17. Fungal infections are rare in healthy people • Immune system usually controls growth • Soil source is typical • Can be accidental (after an earthquake, e.g., Coccidioidesimmitis, “Valley fever”

18. Histoplasma, a dimorphic fungus • Spread by droppings from birds or bats (do not get sick themselves) • “spelunkers’ disease” • TB-like symptoms • Recovery usually spontaneous, but slow • What would be preferred drug treatment?

19. Summary • Respiratory system can host a variety of microbes • Normal flora in “restricted areas” • Susceptibility depends on age, immune system • Some organisms are adept at evading immune system • Damage generally due to cytotoxicity and inflammation • Vaccines are available for some organisms