Streptococcus Pneumoniae Prevention And Vaccination Flashcards
(34 cards)
Immune complexes involved in killing of S pneumoniae
MAC1
FcgammaR
NADPH oxidase complex
Neutrophil extracellular traps
MAC1
C3b receptor on macrophages
Initiates phagocytosis
FcgammaR
On macrophages
For IgG-opsonised bacteria
NADPH oxidase complex
Generates reactive oxygen and nitrogen radicals
Neutrophil extra cellular traps
Nets extruded by neutrophils
DNA, cathelicidins
Location of asymptomatic S pneumoniae replication
Nasopharynx
Removal of C3b opsonised bacteria
Red blood cells express C3bR
Bind C3b opsonised bacteria
Splenic macrophages remove aged red blood cells, with bound antigen-C3b complexes
T cell independent antigen
Polysaccharide
Eg: bacterial capsule
Cells that detect polysaccharide capsule
CD5+ B1 B cells
Why is there little memory response to S pneumoniae?
Only B1 B cells detect capsular antigen (no T cell response)
B cell secretes IgM, limited isotype switching to IgG (no Th response)
No memory
Effective S pneumoniae vaccine design
Need conjugation, so that B cells make antibodies against polysaccharides, T cell receptors against protein epitopes
Results in isotype switching
Issues with conjugates vaccines
Expensive
Around 50 tests on vaccine required before ready
Serotype replacement
Non-vaccine serotype replaces serotype vaccinated against
Features of the ideal prophylactic S pneumoniae vaccine
IgG secretion in blood, meninges
IgA secretion on mucosal surfaces
Features of the ideal therapeutic S pneumoniae vaccine
Effective phagocytosis in spleen, tissues
Production of antibodies against capsular antigens
First pneumococcal vaccine
1911
Whole cell killed vaccine
Second pneumococcal vaccine
1983
Pneumococcal polysaccharide vaccine
Polysaccharide from 23 most common serotypes
– Protects against >80% of pneumococcal disease worldwide
Efficacy of polysaccharide pneumococcal vaccine
Limited
Short-lived protection, as no memory response stimulated
~80% reduction in disease among immunocompetent adults
Reason for lack of memory response from polysaccharide vaccine
No Th cell induction for isotype switching
How do Th cells help B cells in antibody production?
1)
2)
1) Costimulation - CD40, CD40L
2) Providing a cytokine environment to stimulate isotype switching
Th cell activation
APC presents antigen on MHC class II CD80, CD86 (APC) interacts with CD28 (Th cell) APC secretes cytokines
T cell dependent antigen response 1) 2) 3) 4) 5) 6)
1) Protein antigens
2) No repeating epitopes
3) Response in infants
4) Isotype switching
5) High affinity antibodies produced
6) Memory cells produced
T cell independent antigen response 1) 2) 3) 4) 5) 6)
1) Polysaccharide antigens
2) Repeating epitopes
3) No response in infants
4) No/limited isotype switching
5) Low affinity antibodies
6) No memory cells
How to generate a T-cell response from a polysaccharide vaccine
Conjugate a protein epitope onto the relevant polysaccharide