Respiratory Tract Pathogens Flashcards
What causes diphtheria?
Gram-positive rod
Corynebacterium diphtheriae
Extracellular toxigenic bacterium
Where does the gene for diphtheria toxin come from?
Carried on bacteriophage and inserted into bacterial chromosome
What controls the diphtheria toxin gene?
Bacterial transcription factor DtxR
Represses gene expression when bound to iron
Transcription turned on in host where iron concentration is low
What part of the respiratory tract does diphtheria colonise?
The nasopharynx
What does the diphtheria toxin cause?
- Intense local inflammation
- Damage to mucosal cells
- Growth of bacteria in inflammatory exudate
- Formation of pseudomembrane - occludes airway
- Irregular heartbeat, coma, death
How does diphtheria toxin enter cells?
Receptor mediated endocytosis
B binds to heparin-binding epidermal growth factor
What is furin?
A host protease that nicks the A-B polypeptide, but the components remain attached by a disulphide bridge
How does diphtheria toxin A translocate into the cytosol?
Acidification of endosome by V-ATPase triggers B-dependent translocation of A across vesicle membrane into cytosol
What does Streptococcus pyogenes cause?
Pharyngitis
Where does S. pyogenes colonise?
Throat epithelium
What proteins does S. pyogenes produce?
- Surface M protein
- C5a peptidase
- Streptolysins O and S
- Pyogenic toxins
- Hyaluronidase
- Streptokinase
- DNAse
What causes strangles?
Streptococcus equi
Characterised by purulent nasal discharge and abscesses in lymph nodes in neck
What is bastard strangles?
Systemic strangles
Recovered horses are carrier state
Where does pneumonia colonise?
Nasopharynx
Migrates to lower respiratory tract
How does pneumonia resist removal by mucous and ciliated cells?
- Pneumolysin
2. Secretory IgA protease
How does pneumonia avoid phagocytosis by alveolar macrophages?
- Pneumolysin
2. Polysaccharide capsule
Where does pertussis colonise?
Respiratory epithelium
How does pertussis damage epithelial cells?
- Lipid A
- Pertussis toxin
- Adenylate cyclase that mimics host AC
What causes pneumonic plague?
Yersinia pestis
What symptoms does the plague cause?
- Haemorrhagic inflammation
- Spread to blood and lung
- Multi-organ failure
- Necrotic lesions
What virulence factors does Y. pestis have?
- Antiphagocytic capsule
- Protein toxins - YopP and YopT
- LPS lipid A
What makes the coat of M. tuberculosis impermeable?
Waxy acid-fast coat
Contains mycolic acid
Resistant to drying and disinfectants
How does M. tuberculosis spread?
Spread by small droplets
Ingested by alveolar macrophages
Inhibits phagosome-lysosome fusion to prevent intracellular killing
Multiplies in macrophages
Crosses alveolar epithelium when macrophages lyse
Enters lymphatics and spread around body
What protein facilitates dissemination of TB in body?
ESAT6
Pore-forming toxin
Interferes with macrophage signalling pathways
Down-regulates production of ROS
What is the immune response to TB?
TH1 cells activate macrophages via IFNγ
TNFα secretion and production of NO
What is the basis of the tuberculin skin test?
CD4+ T cell activity
What does persisting TB infection cause?
Type IV granulomatous inflammation
Aggregates of activated macrophages, fibroblasts and lymphocytes wall off pathogen
Granulomas show ongoing necrosis, repair and inflammation
Concentrated release of lytic enzymes results in caseous necrosis (cheese-like) - aids spread (miliary TB)
