B4.072 Streptococcus Pneumoniae Flashcards
what are bacterial capsules made out of
polysaccharides
who cannot mount an Ab response against bacterial capsules?
< 2 y/o
not full response until age 6
what functions of the immune system are reduced by capsules
opsonization and phagocytosis
what immune cells don’t react to capsules?
T cells
which antibody classes are produced against capsules
IgM
IgG2
issue with IgM against capsule
activates complement but has low affinity
issue with IgG2 and capsule
poor at opsonization
which bacteria produces a hyaluronic capsule
Group A strep
what is the issue with the hyaluronic acid capsule
weakly immunogenic
similar to hyaluronic acid in connective tissue
may bind to CD44 in pharynx
what is tricky about the type B Neisseria meningitides capsule
contains sialic acid residues, similar to those in human cells
inhibits Ab production and alternative complement pathways
what is slime?
a carb coat around bacteria that can be less well defined than a capsule
viscous and sticky
what is the function of slime?
allow bacteria to attach to surfaces (catheters, teeth)
can be used to glide
generic term for capsules or sline
glycoalyx
bacillus anthracis capsule composition
poly D glutamic acid
what are used to serotype bacteria
capsule
what is the downside to serotyping bacteria by capsule?
S.pneumo and N.meningitides can swap capsule types between strains
how can capsule types be swapped?
transformation
bacteria take in DNA from the environment (from dead, pathogenic s.pneumo)
bacteria that can naturally carry out transformation
competent
s. pneumo is competent
what % of pathogenic strains of s.pneumo have a capsule
100%
aside from evading immune system, how else can capsules help bacteria survive?
prevent desiccation
able to survive in harsher environments
which immune functions are inhibited by the difficulties of producing Abs to bacterial capsule
T cell responses
antibody opsonization
activation of classical complement pathway
how are t cell responses inhibited by capsules
carbohydrates not presented by MHC to T cells (too similar to what is native to our bodies)
how is antibody opsonization inhibited by capsules?
can respond to carbs, but just not good at opsonizing it
don’t develop memory B cells
how do we eventually produce immunity to encapsulated bacteria?
when they die, they expose their protein content
immune response is produced to this protein content
becomes protective at age 6
major encapsulated pathogens
s. pneumo
k. pneumoniae
Hib
p. aeruginosa
n. meningitides
Cryptococcus neoformans (yeast)
how do pneumococci invade?
spread by aerosol
harbored in nasopharynx
interaction most commonly leads to clearance and serotype-specific immunity
common pneumococcal manifestations in children
otitis media
invasive pneumococcal disease
spread to lungs and bloodstream
most serious development of pneumococcal disease
meningitis
what molecules allows for invasion of pneumococcus at the cellular level
phosphorylcholin (PCho)
on cell wall of teichoic acid of pneumococci
what is the function of PCho?
mimics PAF and binds to host cell PAFr
leads to uptake of bacteria into a vesicle and transmigration across epithelial or endothelial barrier
what works against this PCho binding and bacterial entrance?
innate immune elements
CRP binds to PCho on bacteria
surfactant contains abundant PCho
inhibit bacterial contact with host cell
what are vaccines against capsulated pathogens based on?
immunity to the capsule
who cannot produce protective Abs to capsular vaccines?
young children
how are vaccines against capsulated pathogens made?
capsular polysaccharide is conjugated to another immunogenic molecule (diphtheria toxoid, tetanus toxoid)
how does the immunogenic molecule help the body produce a response to the polysaccharide capsule?
generates a strong T cell response and class switches Abs to produce memory response against carbohydrates
how is the polysaccharide capsule processed and responded to when it is unconjugated?
cross links BCR on B cells
drive production of IgG2, IgM
not very useful
no memory response
how is the polysaccharide capsule processed and responded to when it is conjugated?
processed by polysaccharide specific B cell
peptides are presented to carrier peptide specific T cells
results in T cell help for production of both plasma cells and memory B cells
which pathogens have conjugated vaccines in place?
s. pneumo
n. meningitides
Hib
influenza
leading cause of CAP
s. pnuemo
900,000 per year in US
kills 50,000 kids worldwide per year
what groups are particularly susceptible to s.pneumo pneumonia
alcoholic and HIV patients
why are HIV patients at high risk for s. pnuemo when the response is primarily from B cells and neutrophils, not T cells?
need T cells to activate B cells and stimulate them to produce Abs or class switch
characteristics of s. penumo
gram + cocci that grow in pairs/chains a hemolytic catalase neg positive quelling test soluble in bile salts susceptible to optochin
pathophysiology of illness from s. pnuemo
invasive disease may occur upon acquisition of a new epithelium serotype
strong association with viral illnesses
viral infections increase pneumococcal attachment to receptors on activated respiratory epithelium
what is pneumolysin?
produced by s. pnuemo
toxic to mammalian cell membranes by inducing pored
can induce lysis in neutrophils
predisposing conditions for pneumococcal infection
overcrowded conditions age (old or young) alcohol viral illness immunodeficiency
what causes pneumococcal symptoms?
largely due to inflammatory response
- can cause pain by increasing pressure (otitis media)
- interfere with oxygenation of blood (pneumonia)
- -interfere with cerebral function (meningitis)
distinctive symptoms and signs of pneumococcal pneumonia
cough and rust colored sputum
fever
radiographic infiltrate
WBC findings in pneumococcal pneumonia
exceeds 12,000 in majority of pts
neutrophil leukocytosis
what % of pneumonia infections have pos blood cultures
25%
2 key factors in immunity against s. pneumo
phagocytosis by neutrophils
MAIN: opsonization by Ab or complement
discuss the differences in opsonization in naïve vs exposed individuals
naïve: poor response
exposed: protective IgG and IgA
what substances are found in the s. pneumo wall and what can they do?
teichoic acid
peptidoglycan
C substance
-all can activate alternative complement pathway (CRP can too)
why does s.pneumo produce an IgA1 protease?
IgA can activate alternative complement cascade
IgA1 is the predominant form of Ab found in the blood
inhibits this immune response
main defense mechanisms for s.pneumo
- pneumolysin
- IgA1 protease
- capsule
- inhibits innate an acquired immunity
- prevents T cell immunity
- inhibits phagocytosis due to lack of suitable Ab or complement
- prevents CRP binding to PCho and activating complement - competency
why is TLR9 important?
detect unmethylated CpG from bacteria/viruses
when s.pneumo is broken down, DNA is released and taken up by phagocytes, interacts with TLR9 to mount immune response
how does s.pneumo stimulate macrophages and dendritic cells?
TLR2 (peptidoglycan and lipopeptides)
acute phase response
fever
raised CRP
raised ESR
what can TLR9 eventually activate?
dendritic cells
leads to production of IL-12, TNFa, IL-6, IL-1
which cytokines produce Th17 cells?
IL-23
TGFB
IL-6 (main one in acute phase)
what do Th17 cells do
activate neutrophils
