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PRINCIPLES OF RESPIRATORY DEFENSES AND INFECTIONS

PRINCIPLES OF RESPIRATORY DEFENSES AND INFECTIONS. Elizabeth Wasserman Clinical Microbiologist, Pathcare Laboratories Extraordinary professor, Division of Medical Microbiology, Stellenbosch University. Basic anatomy. Etiology of respiratory infections. Viruses Bacteria Fungi.

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PRINCIPLES OF RESPIRATORY DEFENSES AND INFECTIONS

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  1. PRINCIPLES OF RESPIRATORY DEFENSES AND INFECTIONS Elizabeth Wasserman Clinical Microbiologist, Pathcare Laboratories Extraordinary professor, Division of Medical Microbiology, Stellenbosch University

  2. Basic anatomy

  3. Etiology of respiratory infections • Viruses • Bacteria • Fungi

  4. Routes of infection • Patient’s own micro biome (normal flora) • Pathogens transmitted (droplet or airborne) • From other persons • From the environment including other species

  5. RESPIRATORY INFECTIONS Divided into: • Upper respiratory tract infections • Lower respiratory tract infections Division is the larynx. Normal flora is found above the larynx, while the environment below the larynx is sterile under normal conditions.

  6. Concerning the micro biome of the respiratory tract: • note that the upper and the lower respiratory tract forms a continuum for infectious agents. • Organisms are encountered in biofilms or even intracellularly

  7. Normal defence mechanisms against infection: • Innate • Acquired/ adaptive

  8. Innate defenses - Ciliated epithelia of the nose and sinuses. - lysozyme - normal flora • Protection of respiratory tract: coughing and sneezing

  9. Ciliated epithelia • Mucus traps particles • This is moved along by cilia to be excreted or trapped in goblet cells

  10. Lysozyme(muramidase) • Family of enzymes • Also found in tears, saliva and the cytoplasmic granules of polymorphonucliar lymphocytes • Natural antimicrobial substance secreted by mucosa • Acts on cell wall of bacteria, resulting in lysis of cells • Broad spectrum

  11. normal flora • Competition for space: binding sites • Competition for essential nutrients • Producing inhibitory substances, such as colicins

  12. Normal flora of the upper respiratory tract 1. Commonly carried bacteria: Streptococcus viridans - groupNeisseria spp. DiphtheroidsAnaerobiesecocci, fusiforme & Bacteroides2. Bacterial pathogens that can be carried asymptomatically: Streptococcus pyogenes Streptococcus pneumoniaeHaemophilusinfluenzaeCorynebacteriumdiphtheriae Moraxella catarrhalis3. Organisms associated with colonization as a result of antimicrobial therapy: Coliforms - Klebsiella spp., E. coli, etc. Pseudomonas spp. Candida albicans

  13. Specific/acquired immune system • Cell mediated • Immunoglogulins ect

  14. IgA • Immunoglobulin synthesized by the lymphoid aggregates (organized as adenoids, tonsil, Pyer’s patches, or less organized in lamina propria and lung). Together these structures are known as MALT: mucosal associated lymphoid tissue. • Secreted on the surface of the mucosa • Binds antigens of pathogens • Prevents adhesion and therefore colonisation • Allows wandering macrophages with surface receptors for IgA to capture these complexes and to ingests pathogens

  15. Factors that help bacteria to survive in the respiratory tract: • Ability to adhere to respiratory mucosa • Interference with ciliar function by secreting ciliostatic/ciliotoxic molecule • Penetrates cells e.g. fusion protein in viral envelope • Capsules: prevents opsonization and phagocytosis • Interfere with complement-mediated phagocytosis e.g. M protein of S. pyogenes • Persistence in phagocytes: leucocidins, antiphagocytichemolysins (staphylococci, streptococci) • Inhibit lysosomal fusion eg. M. tuberculosis • Destroy antibody e.g. IgA proteases secreted by H. influenzae and streptococci • Fc receptor on microbial surface leads to antibody binding upside down, e.g. Protein A of staphylococci • Switch on T or B cells non-specifically e.g. staphylococcal toxins and M. pneumonia. This produces an ineffective immune respons • Vary microbial antigens: influenza virus, streptococci, pneumococci

  16. The pathogenesis of a typical respiratory tract infection • Breach in local immune responses: • Cold air • Viral infection • Smoke • Allergies • Aspiration • Intubation • Mechanical obstruction or trauma

  17. Swelling of mucosa • Paralysis of cilia • Obstruction of drainage • Accumulation of nutrient rich fluid • Overgrowth of normal flora

  18. Routes of respiratory tract infections • Endogenous (Streptococcus pneumonia, Haemophilusinfluenzae) • Exogenous (TB, influenza virus ect)

  19. Scope of respiratory tract infection Otitis media Common cold Sinusitus Pharyngitis croup Whooping cough Epiglottitis Bronchitis, bronchiolitis Pneumonia Lung abscess Empyema

  20. Basic microbiology of common respiratory tract pathogens (bacteria)

  21. S. pneumoniae • Gram positive diplococci • Capsulated • Alpha-hemolytic on bloodagar • Often less susceptible to penicillin (changes to the PBP target)

  22. S. pyogenes • Gram positive cocci in chains • Beta-hemolytic on bloodagar • Pen sensitive 100% • Main résistance problems: macrolides.

  23. M. catarrhalis • Gram negative cocci • Almost always produces beta-lactamase

  24. S. aureus • Gram positive cocci in clusters • Highly virulent • MSSA/MRSA?

  25. So-called ‘atypicals’: • Mycoplasma pneumoniae • Chlamydiophora pneumoniae • Legionella

  26. A bid more about the atypicals (as you have not encountered them in the other systemic modules)

  27. Mycoplasma pneumoniae Mycoplasmas: • Smallest prokaryotic organisms that can grow in cell-free culture media • Family Mycoplasmatacea consists of > 100 species of Mycoplasma and 6 species of Ureaplasmas. • Widespread in nature, specific human pathogens.

  28. Chlamydophila pneumoniae Chlamydophila in general: • Small Gram-negative obligate intracellular bacteria • No peptidoglycan in their cell wall, and unable to produce their own ATP (energy parasites) • Stain poorly with Gram stain. Immunofluorescend microscopy (using specific AB tagged with fluorescent dye) is most useful

  29. Legionella pneumophila • Gram negative rods, natural habitat is water • Man is infected accidentally and the disease is not transmissible from person to person • Intracellular infection

  30. Fungal pathogens of the respiratory tract: • Aspergillus (allergic, fungus ball or invasive)

  31. Pathogens that may cause lung abscess: • Mixed gram negatives and anaerobes • Streptococcus millirigroup • Parasites: Entamoebahystolytica, Echinococcus granulosis

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