1. Pneumonia

2. Barriers to infection: Epiglottis: protects airway from aspiration.
Cough reflex*.
Mucociliary escalator.
Alveolar macrophage & antimicrobial. compounds: lysozyme, lactoferrin, complement and IgA.
Pneumonia:
Inflammation of the lung parenchyma: Inflammation of alveoli, alveolar ducts, bronchioles, and interstitial tissue of lung, induced by microbial invasion of natural barriers.
Alcohol consumption and cigarette smoking weaken the cough reflex and decrease the function of alveolar macrophages.

3. Classification of pneumonia:
Clinical Classification:
Acute: less than three weeks duration
Chronic pneumonias.
Acute pneumonia is further classified according to place where it was acquired, source of transmission, and etiology.

4. Classification of Acute Pneumonia:
Community acquired:
Person to person
Bacterial:
Classical bacterial pneumonia
Atypical bacterial pneumonia
Viral pneumonia
Animal, or Environmental Exposure.
Nosocomial acquired.

5. Community-acquired acute pneumonia: Person-to-Person:
A- Classic bacterial pneumonia:
Streptococcus pneumoniae.
Haemophilus influenzae.
Klebsiella pneumoniae.
Moraxella catarrhalis.
Aspiration pneumonia* (mixture of bacteria including gram negatives, anaerobes and Staphylococcus aureus).
*From GIT, lead to abscess formation.

6. B- Atypical bacterial pneumonia: Chlamydophila pneumoniae
Person to Person:
B- Atypical bacterial pneumonia:
Chlamydophila pneumoniae
Mycoplasma pneumoniae.
C- Viral pneumonia:
Influenza virus type A, B, and C
Coronaviruses.
Others: RSV, measles, adenoviruses, CMV….. N

7. Environmental or Animal Exposure:
Legionellosis.
Tularemia.
Plague.
Q fever.
Anthrax.

8. Streptococcus pneumoniae :
Reservoir: nasopharynx of children and adults.(patients or asymptomatic carriers).
Transmission: droplets inhalation.
Pathogenesis and microbial virulence:
Colonization of the nasopharynx then spread to the bronchi and alveoli.
Polysaccharide capsule resist phagocytosis.
Production of pneumolysin: cholesterol-binding toxin; epithelial cell-damage.
Production of hydrogen peroxide; cell damage, and inhibition of other bacteria.
Inflammation: production of cytokines; TNFα,IL-1, IL-8 by alveolar macrophage
Virulence factors: pneumolysin, H2O2 and the capsule
Catalase negative so it’s metabolism generates copious amount of H2O2

9. (stages of pneumonia):
Filling of alveoli by fluids*: many bacteria, and few inflammatory cells.
Early consolidation* stage; infiltration of alveoli by neutrophils, activation of complement and CRP which interact with bacterial teichoic acid. (battle b/w the bacteria and the immune system).
Late Consolidation stage: heavy infiltration by neutrophils which kill the microbe helped by the specific Ab and complement, (Hepatization).
Infection eradication (resolution): Replacement of neutrophils by alveolar macrophages.
Clinical presentation: Acute lobar pneumonia.
The bacteria stimulate outpouring of fluids + inflammation
تماسك, تقوية, صلابة, .....

10. Classic bacterial pathogenesis:

11. Lobar Pneumonia

12. Complications of Streptococcus pneumonia: Local complications:
Pleural effusion; Outpouring of fluid into pleural space in 25% of cases.
Empyema (pus in the pleura): in 1% of cases, require drainage of fluid.
Systemic complications:
Bacteremia (pneumococcemia): through lymphatic vessels of the lung to thoracic duct.
Positive blood culture in only 25% of cases (transient bacteremia).
Defense: humoral factors and lymphatic system to remove the bacteria from the blood.
Meningitis esp. in splenectomy, sickle cell anaemia N
When the spleen is not present (asplenia), IgG and C3b are still bound to bacteria, but they cannot be removed from the blood circulation due to the loss of the splenic macrophages.

13. Diagnosis of S. pneumoniae:
Clinical specimens:
Sputum, transtracheal aspirate, broncheoalveolar lavage or lung biopsy.
Direct Microscopy:
Streptococcus pneumoniae are Gram positive lanceolate (lancet shaped) diplococci arranged in pairs or chains, and capsulated.
Cultural characteristics:
Facultative anaerobic bacteria, alpha hemolytic on blood agar, optochin sensitive.

14. Direct Microscopy: Gram positive capsulated cocci

15. Blood agar: α hemolysis & optochin sensitive
Streptococcus
pneumoniae
Streptococcus mitis

16. Haemophilus influenzae
-Gram negative coccobacilli, rod-shaped to pleomorphic.
- Epiglottitis, tracheobronchitis and pneumonia. N

17. Isolation of Haemophilus influenzae :
-Aerobic or facultative anaerobic bacteria.
-Isolated on chocolate agar or factor X (hemin) and factor V (NAD).
-Satellitism phenomenon.

18. Satellitism around S.aureus.

19. Treatment of S. pneumoniae and H. influenzae: Beta-lactam antibiotic.
If the patient is allergic to penicillin or the bacteria is not sensitive: macrolide or fluoroquinolones.
Penicillin-resistant streptococcus due to mutation in penicillin-binding protein by transformation.
Vaccine:
-Conjugated capsular antigen vaccines for S. pneumoniae and H. influenzae type b. N

20. Atypical bacterial pneumonia:
Chlamydophila pneumoniae:
Infective stage: Elementary bodies.
-Target cells: columnar epithelial cells, endothelial cells of the vessels and macrophages.
- Receptor-mediated endocytosis (intracellular infection).
- Lymphocytic infiltration; IF-γ creates persistence infection by slowing the growth of the RB.
Diagnostic stage: Reticulate bodies.

21. Life cycle of C. pneumoniae

22. Clinical presentation:
Acute tracheobronchitis.
Bronchopneumonia (patchy infiltrates on radiography).
C. pneumoniae is associated with Coronary artery disease (CAD):
Adults with CAD have a high antibodies titer against this bacterium.
The microbe can be isolated from atherosclerotic lesions.
The microbe established CAD in animal model studies.

23. bronchopneumonia

24. Immunofluorescent microscopy for antigen and antibodies detection.
Diagnosis:
Immunofluorescent microscopy for antigen and antibodies detection.
PCR.
Treatment:
- Macrolide: Long-term Cmax (maximum serum concentration) of azithromycin.
- Or doxycycline for 7 days.
- Pregnant women: erythromycin or azithromycin. N

25. Mycoplasma pneumoniae:
Smallest prokaryotes that lack cell-wall.
Infect mainly individuals aged 5-20 years old.
Pathogenesis: Tip structure mediated attachment to carbohydrate containing receptor on columnar epithelial cells.
The infection is not highly destructive but the ciliary function is impaired.
Exotoxins:
ADP-ribosyltransferase: inhibition of neutrophils chemotaxis and phagocytosis.
Vacuolating toxin: apoptosis of ciliated cells.
Monocytic infiltration. (few neutrophils) N

26. Clinical presentation: Tracheobronchitis (persistent dry cough).
Bronchopneumonia; (infiltration of monocytes with few neutrophils); patchy infiltrate on radiography.
In 50% of severe mycoplasma infections; mild-autoimmune hemolytic anemia* due to cold hemagglutinin formation.
Complications:
Encephalitis, renal disease and arthritis (antibody complex), autoimmune thrombocytopenic purpura** (erythema multiforme). N
* IgM binds to the RBC and cause them to agglutinate, very few patients develop symptoms.
** Type 4 hyper sensitivity reaction: cell-mediated immune process directed against bacterial antigens deposited in the skin lesions.

27. N

28. Diagnosis: -Direct: PCR or Immunofluorescent microscopy
Diagnosis: -Direct: PCR or Immunofluorescent microscopy. -Indirect: serology: Complement fixation or cold agglutinin test. Treatment: -Macrolide. -Resistance strains; Tetracycline or Fluoroquinolones.