Streptococcus Pneumonia (pneumococcus)

1. Gram positive 'lancet-shaped' diplococci--Note: Catalase NEGATIVE
2. Alpha (partial) hemolytic on blood agar plate. Note: Optochin SENSITIVE, Bile SOLUBLE

Both are alpha-hemolytic and catalase negative, but S. pneumonia is also optochin sensitive (won't grow around an optochin disc) and bile soluble (will lyse in broth or on agar with bile added)

1. Polysaccharide capsule (innate immune evasion)2. Pneumolysin (toxin)3. Lipoteichoic acid (LTA) and teichoic acid (Gram+ cell wall components)4. IgA1 protease (acquired immune evasion)

Antiphagocytic (disrupts alternative complement pathway, preventing opsonization)

1. It is cytotoxic in that 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. pneumonia 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)

Autolysis - it is not secreted. Note: Relatively few bacteria lyse, and they catalyze the amplification cycle.

1. Activate complement: after lysis, these polysaccharides are no longer encapsulated, and are targets for C3b (alternative complement system)
2. Pro-inflammatory (PMN recruitment)

They cleave IgA1 at the hinge region, helping S. pneumonia evade acquired immunity.Note: IgA's live on mucous membranes.Note: IgA2 is unaffected because it has no hinge region.

It triggers an acute inflammatory response, mostly resulting from activation of the complement system. (See amplification cycle flashcard)

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. pneumonia to grow --> autolysis --> amplification of cycle.
Note: PMNs are useless

1. S. pneumonia have thick, antiphagocytic capsule.2. Pneumolysin kills PMNs

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 repetitious 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

Induce production of anti-capsular antibodies (capsule is the main virulence factor; without it, S. pneumonia is not virulent).

The polysaccharide vaccine taps into the host's T-cell independent antibody production mechanism by introducing polysaccharide antigens from 23 of the 80+ S. pneumonia serotypes.
Since this is not effective in children under 2 (T-cell independent mechanism isn't mature), we use the conjugate vaccine.
This conjugate vaccine induces T-cell help, which leads to B cell differentiation into plasma cells and gives the added bones 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 polysaccharide. Note: 98% effective against the 7 (13) serotypes in Prevnar 7 (Prevnar 13)

Herd immunity: we are knocking out the reservoir.