B4.072 Streptococcus Pneumoniae Flashcards

1
Q

what are bacterial capsules made out of

A

polysaccharides

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2
Q

who cannot mount an Ab response against bacterial capsules?

A

< 2 y/o

not full response until age 6

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3
Q

what functions of the immune system are reduced by capsules

A

opsonization and phagocytosis

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4
Q

what immune cells don’t react to capsules?

A

T cells

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5
Q

which antibody classes are produced against capsules

A

IgM

IgG2

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6
Q

issue with IgM against capsule

A

activates complement but has low affinity

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7
Q

issue with IgG2 and capsule

A

poor at opsonization

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8
Q

which bacteria produces a hyaluronic capsule

A

Group A strep

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9
Q

what is the issue with the hyaluronic acid capsule

A

weakly immunogenic
similar to hyaluronic acid in connective tissue
may bind to CD44 in pharynx

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10
Q

what is tricky about the type B Neisseria meningitides capsule

A

contains sialic acid residues, similar to those in human cells
inhibits Ab production and alternative complement pathways

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11
Q

what is slime?

A

a carb coat around bacteria that can be less well defined than a capsule
viscous and sticky

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12
Q

what is the function of slime?

A

allow bacteria to attach to surfaces (catheters, teeth)

can be used to glide

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13
Q

generic term for capsules or sline

A

glycoalyx

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14
Q

bacillus anthracis capsule composition

A

poly D glutamic acid

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15
Q

what are used to serotype bacteria

A

capsule

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16
Q

what is the downside to serotyping bacteria by capsule?

A

S.pneumo and N.meningitides can swap capsule types between strains

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17
Q

how can capsule types be swapped?

A

transformation

bacteria take in DNA from the environment (from dead, pathogenic s.pneumo)

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18
Q

bacteria that can naturally carry out transformation

A

competent

s. pneumo is competent

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19
Q

what % of pathogenic strains of s.pneumo have a capsule

A

100%

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20
Q

aside from evading immune system, how else can capsules help bacteria survive?

A

prevent desiccation

able to survive in harsher environments

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21
Q

which immune functions are inhibited by the difficulties of producing Abs to bacterial capsule

A

T cell responses
antibody opsonization
activation of classical complement pathway

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22
Q

how are t cell responses inhibited by capsules

A

carbohydrates not presented by MHC to T cells (too similar to what is native to our bodies)

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23
Q

how is antibody opsonization inhibited by capsules?

A

can respond to carbs, but just not good at opsonizing it

don’t develop memory B cells

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24
Q

how do we eventually produce immunity to encapsulated bacteria?

A

when they die, they expose their protein content
immune response is produced to this protein content
becomes protective at age 6

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25
Q

major encapsulated pathogens

A

s. pneumo
k. pneumoniae
Hib
p. aeruginosa
n. meningitides
Cryptococcus neoformans (yeast)

26
Q

how do pneumococci invade?

A

spread by aerosol
harbored in nasopharynx
interaction most commonly leads to clearance and serotype-specific immunity

27
Q

common pneumococcal manifestations in children

A

otitis media

28
Q

invasive pneumococcal disease

A

spread to lungs and bloodstream

29
Q

most serious development of pneumococcal disease

A

meningitis

30
Q

what molecules allows for invasion of pneumococcus at the cellular level

A

phosphorylcholin (PCho)

on cell wall of teichoic acid of pneumococci

31
Q

what is the function of PCho?

A

mimics PAF and binds to host cell PAFr

leads to uptake of bacteria into a vesicle and transmigration across epithelial or endothelial barrier

32
Q

what works against this PCho binding and bacterial entrance?

A

innate immune elements
CRP binds to PCho on bacteria
surfactant contains abundant PCho
inhibit bacterial contact with host cell

33
Q

what are vaccines against capsulated pathogens based on?

A

immunity to the capsule

34
Q

who cannot produce protective Abs to capsular vaccines?

A

young children

35
Q

how are vaccines against capsulated pathogens made?

A

capsular polysaccharide is conjugated to another immunogenic molecule (diphtheria toxoid, tetanus toxoid)

36
Q

how does the immunogenic molecule help the body produce a response to the polysaccharide capsule?

A

generates a strong T cell response and class switches Abs to produce memory response against carbohydrates

37
Q

how is the polysaccharide capsule processed and responded to when it is unconjugated?

A

cross links BCR on B cells
drive production of IgG2, IgM
not very useful
no memory response

38
Q

how is the polysaccharide capsule processed and responded to when it is conjugated?

A

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

39
Q

which pathogens have conjugated vaccines in place?

A

s. pneumo
n. meningitides
Hib
influenza

40
Q

leading cause of CAP

A

s. pnuemo
900,000 per year in US
kills 50,000 kids worldwide per year

41
Q

what groups are particularly susceptible to s.pneumo pneumonia

A

alcoholic and HIV patients

42
Q

why are HIV patients at high risk for s. pnuemo when the response is primarily from B cells and neutrophils, not T cells?

A

need T cells to activate B cells and stimulate them to produce Abs or class switch

43
Q

characteristics of s. penumo

A
gram + cocci that grow in pairs/chains
a hemolytic
catalase neg
positive quelling test
soluble in bile salts
susceptible to optochin
44
Q

pathophysiology of illness from s. pnuemo

A

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

45
Q

what is pneumolysin?

A

produced by s. pnuemo
toxic to mammalian cell membranes by inducing pored
can induce lysis in neutrophils

46
Q

predisposing conditions for pneumococcal infection

A
overcrowded conditions
age (old or young)
alcohol
viral illness
immunodeficiency
47
Q

what causes pneumococcal symptoms?

A

largely due to inflammatory response

  • can cause pain by increasing pressure (otitis media)
  • interfere with oxygenation of blood (pneumonia)
  • -interfere with cerebral function (meningitis)
48
Q

distinctive symptoms and signs of pneumococcal pneumonia

A

cough and rust colored sputum
fever
radiographic infiltrate

49
Q

WBC findings in pneumococcal pneumonia

A

exceeds 12,000 in majority of pts

neutrophil leukocytosis

50
Q

what % of pneumonia infections have pos blood cultures

A

25%

51
Q

2 key factors in immunity against s. pneumo

A

phagocytosis by neutrophils

MAIN: opsonization by Ab or complement

52
Q

discuss the differences in opsonization in naïve vs exposed individuals

A

naïve: poor response

exposed: protective IgG and IgA

53
Q

what substances are found in the s. pneumo wall and what can they do?

A

teichoic acid
peptidoglycan
C substance
-all can activate alternative complement pathway (CRP can too)

54
Q

why does s.pneumo produce an IgA1 protease?

A

IgA can activate alternative complement cascade
IgA1 is the predominant form of Ab found in the blood
inhibits this immune response

55
Q

main defense mechanisms for s.pneumo

A
  1. pneumolysin
  2. IgA1 protease
  3. 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
  4. competency
56
Q

why is TLR9 important?

A

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

57
Q

how does s.pneumo stimulate macrophages and dendritic cells?

A

TLR2 (peptidoglycan and lipopeptides)

58
Q

acute phase response

A

fever
raised CRP
raised ESR

59
Q

what can TLR9 eventually activate?

A

dendritic cells

leads to production of IL-12, TNFa, IL-6, IL-1

60
Q

which cytokines produce Th17 cells?

A

IL-23
TGFB
IL-6 (main one in acute phase)

61
Q

what do Th17 cells do

A

activate neutrophils