Term
What does S. pneumoniae look like:
1. Under light microscope?
2. In culture?
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Definition
1. Gram positive,"lancet-shaped" diplococci
Note: Catalase NEGATIVE
2. Alpha-hemolytic on blood agar plate.
Note: Optochin SENSITIVE, Bile SOLUBLE |
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Term
How do we differentiate S. pneumoniae from S. viridens in culture? |
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Definition
Both are alpha-hemolytic and catalase negative, but S. pneumoniae also optochin sensitive (won't grow around an optochin disc) and bile soluble (will lyse in broth or on agar with bile added). |
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Term
What are the main virulence factors of S. pneumoniae? |
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Definition
1. Polysaccharide capsule (innate immune evasion)
2. Pneumonlysin (toxin)
3. Liptoteichoic acid (LTA) and teichoic acid (Gram+ cell wall components)
4. IgA1 protease (acquired immune evasion) |
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Term
How does the polysaccharide capsule make S. pneumoniae virulent? |
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Definition
Antiphagocytic (disrupts alternative complement pathway, preventing opsonization) |
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Term
How does the toxin pneumolysin work? |
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Definition
1. It is cytotoxic in that it induces host cell lysis by binding cholesterol and multimerizing to form transmembrane pore. Bacterial membranes don't have sterols, so pneumolysin does not affect the S. pneumoniae itself.
Note: This can also disrupt the blood-brain barrier, leading to meningitis.
2. It directly activates complement (in addition to contents of lysed cell, e.g. LTA and teichoic acid). |
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Term
How is pneumolysin released from S. pneumoniae? |
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Definition
Autolysis - it is not secreted.
Note: Relatively few bacteria lyse, and they catalyze the amplification cycle. |
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Term
How to LTA and teichoic acid function as virulence factors of S. pneumoniae? |
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Definition
1. Activate complement: After lysis these polysaccharides are no longer encapsulated, and are targets for C3b (alternative complement system)
2. Pro-inflammatory (PMN recruitment) |
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Term
How do IgA1 proteases act as virulence factors of S. pneumoniae? |
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Definition
They cleave IgA1 at the hinge region, helping S. pneumoniae evade acquired immunity.
Note: IgA's live on mucous membranes, where S. pneumonia colonization occurs
Note: IgA2 is unaffected because it has no hinge region |
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Term
How does S. pneumoniae lead to pneumonia? |
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Definition
| It triggers an acute inflammatory response, mostly resulting from activation of the complement system. (See amplification cycle flashcard.) |
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Term
Describe the S. pneumoniae amplification cycle that leads to fluid accumulation in the lungs. |
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Definition
1. Autolysis leads to complement activation (LTA, teichoic acid, pneumolysin) and inflammation (LTA, teichoic acid).
2. Complement leads to further inflammation (C5a attracts PMNs), vascular permeability (C3a, C4a, C5a trigger histamine release).
3. Fluid accumulation provides broth for S. pneumoniae to grow --> autolysis --> amplification of cycle.
Note: PMNs are useless (capsule, pneumolysin) |
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Term
Why are PMNs not helpful in resolving S. pneumoniae infections? |
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Definition
1. S. pneumoniae has thick, antiphagocytic capsule
2. Pneumolysin kills PMNs |
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Term
What are the host defense mechanisms against S. pneumoniae? |
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Definition
Host develops IgG antibodies to capsular polysaccharides by a T-cell independent mechanism (remember, MHC molecules present peptides, not sugars).
Mechanism: Multiple IgM receptors on B cell bind to the repeitious polysaccharide chain causing receptors to cluster and cross-link, which triggers differentiation to plasma cells.
Note: This mechanism is not mature until age 2, so infants are more susceptible to pneumococcal infections. |
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Term
How do vaccines against S. pneumoniae work? |
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Definition
| Induce production of anti-capsular antibodies (capsule is the main virulence factor; without it, S. pneumoniae is not virulent). |
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Term
What is the difference between the pneumococcal polysaccharide vaccine (Pneumovax) and the conjugate vaccine (Prevnar)? |
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Definition
They polysaccharide vaccine taps into the host's T-cell independent antibody production mechanism by introducing polysaccharide antigens from 23 of the >80 S. pneumoniae serotypes.
Since this is not effective in children under 2 (T-cell independent mechanism isn't mature), we use the conjugate vaccine.
The conjugate vaccine induces T-cell help, which leads to B-cell differentiation into plasma cells and gives the added bonus of memory cells. The antigenic polysaccharide chain is conjugated to a protein (non-toxic diphtheria), so B-cells can take it up and present the peptide and polysaccharide to T-cells (peptide is necessary for MHC loading). The antibodies produced bind to the polysaccharide.
Note: 98% effective against the 7 (13) serotypes in Prevnar 7 (Prevnar 13) |
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Term
Why have we seen a decrease in the elderly population of pneumococcal infections of the serotypes in Prevnar, when Prevnar is only given to young children? |
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Definition
| Herd immunity: we are knocking out the reservoir. |
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Term
Why have we seen decreases in viral pneumonias correlated with pneumococcal vaccination? |
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Definition
| Viral pneumonias are often seen with bacterial pneumonias due to cytokine activation of endothelial cells. Viruses activate endothelial cells, allowing pneumococcal penetration. I don't understand why pneumococcal vaccine would prevent viral pneumonia. |
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Term
Why don't we treat S. pneumoniae with penicillin? |
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Definition
S. pneumoniae is resistant to penicillins due to altered (low-affinity) PBPs.
Note: Mutations are from natural transformation and recombination of PBP genes, forming chimeric genes. Point mutations wouldn't be enough to cause resistance. High levels or resistance require significant alteration of at least 4 PBPs. |
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Term
How do we treat pneumonia caused by S. pneumoniae? |
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Definition
Ceftriaxone (3rd generation cephalosporin). Vancomycin is a last resort.
Note: In reality, when we see pneumonia we also give a macrolide in case it's an atypical pneumonia. |
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