22 - Bacterial Pathogens of the Respiratory Tract Flashcards

1
Q

How do we divide the respiratory tract clinically and what is a key difference between the two?

A

Upper and lower!

upper-non-sterile

lower-sterile

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2
Q

WHat are 5 ways that bacteria and enter/spread into the lower (sterile) respiratory tract

A
  • direct inhalation: determined by particle size
  • aspiration of upper airway contents
  • spread among mucous memebrane surface
  • hematogenous spread
  • direct penetration (ie intratracheal tube)
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3
Q

What are 5 important defense barriers to bacterial infections?

A
  • Ability to filter particles based on size (air flow and vibrissae)
  • mechanical restriction (epiglottis and cough refelx)
  • Mucociliary escalator (propels material away form the lulngs)
  • Respiratory tract secretions (antimicrobial peptides, lactoferrin/transferrin, sIgA antibodies, lysozyme, etc)
  • Localized immune cells and other host factors (phagocytes, immunoglobins, complement)
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4
Q

What are 6 general strategies used by bacterial pathogens of the RT to overcome/subvert host barriers?

A
  • Adherence and/or invasion to/of RT tissues (pili, fimbriae, adhesions)
  • secretion of tissue damaging enzymes (lysins, proteases, elastases)
  • factors that inhibit or neutralize host defense mechanisms (proteases, capsule)
  • Toxins that alter/inactivate host cell functions ribosylte G-proteins and EF-2, phopholipases
  • factors that overstiumlate the immune response superantigens, etc
  • from microcommuniites (biofilms) to resist elimination overproduce plysaccarides (alignate)
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5
Q

What are the 2 possible morphologies of organisms that are gram-positve? Please give one example per morphology.

A

coccus: staphylococcus clusters, streptococcus chains

rod(bacillus): corynebacterium

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6
Q

What is an example of an organism that is acid-fast and what is its morphology?

A

Mycobacterium

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7
Q

What are the 2 possible morphologies of organisms that are gram-negative? Please provide some examples.

A

Coccus: Neisseria

Rod: Pseudomonas, legionella, Haemophilus

Coccobacillus: bordetella

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8
Q

What is the morpholgy of an organism that has no cell wall? Please give an example.

A

Pleomorphic: Mycoplasma

(note this is not mycobacterium. mycobacterium is acid fast rod)

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9
Q

What are the important features of Bordetella pertussis?

morphology/gram stain

aerobe vs anerobe

virulence mechanisms

population of infection

A
  • gram negative coccobacillus
  • strict aerobe
  • produced pertussis toxin (PTx)
  • adheres to cilia of respiratory epithelium and expresses several adhesins including FHA (filamentous hemagglutinin), pertactin, pili
  • bacterium is highly infectious and transmittable
  • primary disease of the young, but adults may be asymptomatic carriers
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10
Q

What disease is associated with Bordetella pertussis? What are its 3 distinct phases? Is there a vaccine?

A

Whooping cough (pertusssis)

3 distinct phases: catarrhal, paroxysmal, convalescence

Vaccine available (acellular against PTx, FHA, pertactin) but possibly is waning in efficacy

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11
Q

what is the mechanism of disease elicitation for B. pertussis?

A

Results in whooping cough!

  • bacteria binds to ciliated wpithelium
  • secretes PTx which alters adenylate cyclase activity
  • ADP ribosylates Gia which induces elevated cAMP production resulting in increased secretions and mucus production
  • other secreted factors damage the mucociliary elevator
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12
Q

What are the important features of corynebacterium?

gramstain/ morphology

virulence factor

anatomical location of infection

population of infection

is there a vaccine

A
  • gram positive arranged in pallisades (unsual organization of bacteria)
  • virulence factor is diptheria toxin (DTx): ADP-ribosylates EF-2 (inhibits protein synthesis)
  • produces pili required for bacterial colonization of upper RT
  • global distribution but uncommon in US and other developed areas due to vaccine
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13
Q

What diseases are associated with corynebacterium?

how is the diease primarily mediated?

A

Psuedomembrane: non-toxin producing strains elicit localized infection resulting in pseudomemebrae

Systemic disease: Toxin- producing strains have a toxin carried on a lysogenic (integrated)bacteriophage. symptoms include fever, sore throat, and malaise

**disease is priamrily mediated by production of diptheria toxin**

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14
Q

WHat is the mechanism of disease elicitation for C. diptheriae?

A
  • pili mediate adherence of bacteria to repiraotry epithelium
  • extensive bacterial replication at surface of epithleium
  • 2 stages: localized invasion and systemic disease (toxin producing strains)
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15
Q

What is the pseudomembrane assciated with C. diptheriae made up of?

A

fibrin, bacteria, and inflamamtory cells

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16
Q

What is the diptheriae vaccine composed of?

A

formalin inactivated diptheria toxin (diptheria toxoid)

because of the vaccine diptheria associated morbidity and mortality has been greatly reduced

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17
Q

What bacterial vaccine is commonly used as a conjugate for other vaccines?

A

Diptheria!

DT-also carrier for conjugate vaccines (Hib)-CRM 197 a point mutation within DT that inactivates the toxin

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18
Q

What are the following important features of Neisseria meningitidis?

gram stain and morphology

virulence factors

anatomical location of inhabitance

A
  • gram negative diplococci
  • oxidase+, catalase+, polysaccharide capsule, and produce pili
  • common inhabitant of the nasopharynx of healthy individuals (most often teens)
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19
Q

What diseases are associated with Neisseria Meningitidis? What population is most often infected? What is the greatest concern?

A

Pharyngitis, Pneumonia (able to cause lower resp infection when aspirated)

usually preceded by respiratory tract infection. often seen in individuals with underlying disease or in kids

greatest cncern is progression to meningitis

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20
Q

What is the mechnaism of disease elicitation for N. meningitidis?

A

breaks through the epithelial layer via its virulence factors and avoids phagocytization by PMNs. If it gets to the blood stream can lead to meningitis

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21
Q

What are the 3 virulence factors for N meningitidis? What is the biologic effect of each?

A
  • capsule-prevent phagocytosis and complement fixation
  • type IV pili- allow colonization of the nasopharyns
  • LOS- lipooligosaccharide: similar to LPS but no repeating O-antigens. Has endotoxin acitivity
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22
Q

Which serogroups is the N meningitidis vaccine developed against? At what age is it adminstered?

A

The vaccine is against the polysaccharide capsule

  • polyvalent vaccine developed against serotypes A,C,Y, W135 administered to individuals >2yrs
  • MCV4-conjugate vaccine for <55 yrs
  • MPSV4 capsule vaccine >55yrs
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23
Q

What are the important factors for streptococcus pyogenes (Group A Strep)?

gram stain/ morphology

virulence factors

A

gram positive cocci arranged in chains

beta-hemolytic, catalse negative

Possesses M protein and has a hyaluronic capsule

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24
Q

What diseases are associated with streptococcus pyogenes (GAS)?

A

Pharyngitis (strep throat): redness and edema of the mucous membranes, fever, purulent exudate, tonsilitis

Scaret fever: streptococcal pharyngitis and an erythematous punctiform rash

25
Q

What is the mechanism of disease elicitation for S. pyogenes? specifically what leads to scarlet fever?

A
  • Surface proteins (M protein, F protein, ,LTS) promote adherence in pharynx
  • Localized tissue destruction due to secreted enzymes
  • scarlet fever is secondary complication. due to pyrogenic exotoxins-superantigens, not bacterial dissemination
26
Q

What are the 7 virulence factors for strep pyogenes and what are thei biologic effects? (I’m sorry to put so much on one card <3)

A
  • Capsule-prevent phagocytosis and complement fixation
  • LTA-binds to epithelial cells
  • M protein: adhesin; antiphagocytic; degrades complement component C3b
  • Pyrogenic exotoxins: mediates pyrogenicity
  • Streptolysin S: lyses leukocytes, platelets and erythrocytes
  • Streptolysin O: Lyses leukocytes, platelelets and erythrocytes

**phew you made it to the end <3 Go you!

27
Q

How do we check for streptococcus pyogenes in clinic besides growing a culture?

A

Rapid Strep Test/ Rapid Antigen Detection Test

membrane on test contains anti-strepA antibody, sample from throat is inserted. a line appears when the antibody on the test combines with the antigens in the sample

28
Q

WHat are the important features of staphylococcus aureus?

gram stain/ morphology

virulence factors

A

Gram positive cocci often in clusters

catalase +, polysaccahride capsule, protein A on surface, many different toxins and cytopathic enzymes

29
Q

What disease is associated with Staphylococcus aureus infection of the RT? How is it acquired and who gets it?

A

Pneumonia-seen mainly in the very young and elderly with underlying pulmonary disease.

acquired via aspiration of oral secretions or hematogenous spread from a different site

30
Q

WHat is the mechanism of disease elicitation of S. aureus?

A
  • normal component of nasopharyngeal flora
  • pulmonary tissue destruction due to secreted enzymes
  • can spread to other infected sites to manifest differes disease symptomology
31
Q

What are the 3 virulence facotrs for S. aureus and what are their biologic effects?

A

Capsule: prevent phagocytosis and complement fixation

LTA: binds to epithelial cells (fibronectin)

Protein A: Binds Fc receptors to inhibit antibody-mediated clearance

32
Q

What are important features of Streptococcus pneumoniae?

gram stain/morphology

virulence factors

is there a vaccine/what is the basis for it

A

Gram positive cocci often in pairs (diplococci)

alpha hemolytic, polysaccharide capsule in the viruelnt strains

more than 90 different capsular serotypes recognized (basis of vaccine)

note there is no lancefield designation- which means not GAS, GBS etc

33
Q

What disease is associated with streptococcus pneumoniae infection of the RT?

A

Lobar pneumoniae, sinusitis, otitis media

34
Q

What is the mechanism of disease elicitation in S pneumoniae?

A

lungs fill with fluid due to tissue damage and over-activation of the immune response

35
Q

What are the 2 virulence factors for S pneumoniae? What are their biologic effects?

A

Pneomolysin: destroy epithelial cells, activates alternative complement pathway, suppresses phagocytic oxidative burst

Capsule: Antiphagocytic

36
Q

What does the S. pneumoniae vaccine target? What are the 2 different kinds?

A

S, pneumoniae vaccine targets the polysaccharide capsule

23-valent polysaccharide capsule vaccine (PPSV23) for adults and at risk adults/kids

13-valent canjugated vaccine (PVC13) for children<2yrs

37
Q

What are the important features of Haemophilus influenzae?

gramstain/ morphology

requirements for growth

virulence mechanisms

A

Small Gram negative rods

requires heme and NAD for growth (grows on chocolate agar)

invasive species possess polysaccharide capsule

uses pili and OMPs to bind respiratory epithelial cells

38
Q

What diseases are associated with infection of H. influenzae in the RT? What strains colonize the upper RT?

A

Pneumonia, sinusitis, otitis, epiglotitis

non-encapsulated strains colonize upper RT

Lower RT infections more common n kids or individuals with underlysing condition

39
Q

What is the mechanism of disease elicitation for H. influenzae? What are we worried about?

A
  • attaches to respiratory epithelium through pili and OMPs
  • gain access to underlying submucosa by invading between epithelium
  • cause induction of localized pro-inflammatory response. concern is systemic infection and spread to CNS
40
Q

What are the 3 virulence factors for H infleunzae? What are their biologic effects?

A

Capsule: prevent phagocytosis and complement fixation

OMPs (HMW1, HMW2): Outer membrane proteins-bind to epithelial cells

LOS-: Lipooligosaccharide: has endotoxin activity

41
Q

Which type of H. influenzae is there a vaccine against? How effective is it?

A

YES!

  • Vaccine to Hib (H. influenzae type B)
  • 3 monovalent conjugate vaccines and combination Hib-conjugate vaccines are available
  • Hib has decreased in children by 99% since vaccine was introduced
42
Q

What are the important features of Mycoplasma pneumniae?

morphology/gram stain

aerobe vs anaerobe

virulence factors

A
  • No cell wall (so does not gram stain) coccoid or pleomorphic (egg like appearance)
  • bound by triple layered membrane containing sterols
  • obligate aerobe
  • produces P1 adhesin
  • smallest free living prokaryote, lifestyle associate with host cells, slow growing
43
Q

What diseases are associated with Mycoplasma pneumoniae infection?

A

Tracheobronchitis and atypical pneumonia

44
Q

What is the mechanism of disease elicitation for M. pneumoniae?

A
  • associates with upper airway epithelial cells through the major adhesion=P1
  • close association causes local accumulation of toxic metabolites, oxidation of lipids
  • binding destroys cilia and inhibits clearance by normal mechanisms resulting in shedding of the bacterium in respiratory secretions
  • induces inflamamtory response which enahnces cell damage via over-secretion of cytokines
45
Q

What are the important features of Pseudomonas aeruginosa?

gram stain/ morphology

virulence factors

where do they grow

A
  • Gram negative rod with single polar flagella
  • oxidase +
  • form in biofilms on surfaces and inanimate objects (catheters)
  • opportunistic pathogen
  • multiple virulence determinants including exotoxins
46
Q

What diseases are associated with infection by Psedomonas aeruginosa?

A

lung infections of cystic fibrosis patients

47
Q

What is the mechanism of disease elicitation for P. aeruginosa?

A
  • opportunistic=must breach normal host defense barriers
  • biofilm formation allows bacteria to resist mmune-mediated clearance
  • produces pilins and other adhesins which promote association with repiratory epithelial cells
  • produces numerous secreted proteins (proteases, exotoxins, endotoxins, DNAses) which directly damage or inactivate host cells
48
Q

WHat are the 2 virulence fators for P. aeruginosa?

A

polysaccharide capsule (alginate): protection from immune system

Exotoxins (ExoA, ExoU, ExoY, ExoS): inactivate or destroy host tissues

49
Q

What are the important features for Legionella pneumophila?

gram stain/ morphology

who does it infect

virulence factors

how is it grown

A
  • Gram negative rod
  • opportunistic pathogen
  • single polar flagella
  • maintained in water supplies and or amoeba in environment
  • grown on special medium
  • produces cytotoxins, hemolysins, endotoxins and lipases
  • typically detected by fluorescent antibody stain
50
Q

What diseases are associated with infection by Legionella pneumophila?

A

Legionaire’s disease: sever pneumonia-like symptoms

Pontiac fever: self-limiting flu like illness

51
Q

What is the mechanism of disease elicitation of L. pneumophila?

A
  • survives inside alveolar macrophages within lungs
  • production of various enzymes (phosphatase, lipase, and nuclease) kills infected host cell
  • little is known about what responsible for difference in disease presentation between Legionaire’s and Pontiac fever
52
Q

What are the important features for Mycobacterium tuberculosis?

gramstain/morphology

contents of cell wall

how does it survive

what kind of infection does it cause

A
  • acid-fast rods (although bacterium is considered gram positive)
  • thick waxy cell wall contianing mycolic acids and lipoarabinomannan
  • survivies in granulomas
  • causes acute or latent infection
53
Q

What diseases are associated with Mycobacterium tuberulosis?

A

Tuberculosis (however, various manifestations)

54
Q

What is the mechanism of disease elicitation by M tuberculosis?

A
  • bacterium survives and persists within host-generated granulomas (latency)
  • reactivates to cause acute disease
  • disease symptomology primarily over-exaggerates host response to infection leading to tissue necrosis
55
Q

What are the virulence factors for M. tuberculosis?

A

Long chain fatty acids (mycolic acids, liparabinomanan): impervious cell envelope helps prevent damage by host compounds (cationic peptides, oxygen radicals, nitric oxide) encountered within granuloma

56
Q

How do we diagnose M tuberculosis and what is the treatment?

A

Diagnostic: PPD skin test (delayed type hypersensitivity), quantiferon test-specific to M. tuberculosis infection

Treatment: multidrug cocktail includin isoniazid (targets mycolic acids) administered over extended period

57
Q

How could infection by influenza Virus A pre-dispose people to bacterial infection?

A

viral infection disrupts airway epithelium, alters normal mechanical clearance, disrupts phagoctic phagocytic function

58
Q

What can be done to prevent infection by Streptococcus pneumoniae?

A

immunize with prenar 13-conjugate vaccine which targets capsule which is a major viruelnce factor

59
Q

Are you sick of bacteria yet?

A

Well you’re in luck bc this deck is OVER! <3