3.21 Flashcards
1
Q
Yersenia pestis, cause of plague
characterization
A
Black death
Gram−
2
Q
Transmission of plague (3)
A
fleas
bubo (infected lymph node with pus): not contagious
• 50-75% mortality if not treated promptly
In 10-20% spread to lungs:
• highly contagious (direct transmission)
• near 100% mortality: black death
3
Q
Francisella tularensis
characterization (2)
A
Gram−
opportunistic zoonosis
(birds, rabbits, tick bites) (bioterrorism)
4
Q
Francisella tularensis
Virulence Factors: (1)
A
Ø intracellular growth in macrophages
(prevents phagolysosome fusion) bacteremia
5
Q
Francisella tularensis
Diseases: rabbit fever, tick fever (2)
A
• ulceroglandular and
oculoglandular tularemia
• pulmonary tularemia
6
Q
Brucella characteriztion (2)
A
Gram−
opportunistic zoonosis by B.melitensis (or bioterrorism)
7
Q
undulant fever (brucellosis, “bangs disease”
A
systemic bacteremia starting from infected lymph nodes
8
Q
skipped
undulant fever
A
Organisms penetrate mucous membranes and are carried to heart, kidneys, and other parts of the body via the blood and lymphatic system; they are resistant to phagocytic killing and grow within these cells
9
Q
Haemophilus influenzae
characterization (2)
A
Gram−
frequently part of oral flora (carrier rate up to 80%)
6 O-antigen serotypes: a – f: type b is most virulent
10
Q
Haemophilus influenzae
Virulence Factors:
A
capsule b
11
Q
Haemophilus influenzaem
Conjugated vaccine
A
against capsule b polysaccharides creates protective IgG, preventing systemic infections Vaccine does not protect against other encapsulated strains and unencapsulated strains
12
Q
Haemophilus influenzae type b infections
cases per year before immunization
decrease after
A
20,000
99.7%
13
Q
before the availability of conjugate vaccines in late 1987 H. influenzae type b was the most common cause of bacterial meningitis in
A
preschool children
14
Q
Without vaccination: systemic diseases
in children) by encapsulated strains: (2
A
- meningitis
* septicemia, cellulitis, epiglottitis
15
Q
Haemophilus influenzae Gram- rods, aerobic / facultatively anaerobic Virulence factors Clinical features Treatment EPIDEMIOLOGY (2)
A
polysaccharide capsule b
pili, adhesins
IgA protease
no capsule: otis media, sinusitis, conjunctivitis, bronchitis, pneumonia capsule B: meningitis, septicemia, cellulitis, epiglottitis
broad-spectrum cephalosporin, azithromycin or fluoroquinolone (>30% ampicillin resistance)
aerosol transmission
respiratory tract in
elderly
16
Q
Legionella pneumophila
characterization (4)
A
Gram−
facultatively intracellular
Growth up to 46C
Relatively resistant to chlorine and other biocides
17
Q
facultatively intracellular (prevents endosome-lysosome fusion; autophagosome-like uptake)
A
Lives and proliferates in the vacuoles of amoebas and
in the endoplasmic reticulum of macrophages
18
Q
Legionnaires disease: how was it disovered
A
infected roof A/C
19
Q
Legionnaire’s disease
Virulence Factors:
A
Ø intracellular growth in alveolar macrophages
no phagolysosomal fusion
20
Q
Legionnaire’s disease
Transmission:
A
aerosol from water sources (living inside amoeba)
No human-to-human transmission
21
Q
Legionnaire’s disease
A
severe pneumonia, necrotic abscesses
especially in immune-compromised and elderly; mortality 20%
22
Q
Listeria monocytogenes (6)
A
• acid-resistant • cold-resistant (psychrotolerant) (growth from 1ºC to 45ºC) • salt-resistant • motile • food-borne pathogen (processed meat like hot dogs, dairy like Brie cheese; 4ºC stored) • facultatively intracellular (enterocytes, macrophages)
23
Q
— is rare (2500 cases/yr)
But exposure is common (10%
asymptomatic carriers)
A
Listeriosis
24
Q
Listeria monocytogenes
VF
A
listeriolysin O
25
listeriolysin O
pore-forming toxin (phagosome escape)
26
Intracellular infections by Listeria monocytogenes
listeria or other bacteria cross the mucous membrane into tissues by passing through M cells
(b) macrophages engulf bacteria
(c) pathogen released from macrophages enters host cells by endocytosis
(d) bacteria move from cell to cell propelled by actin filaments
27
Cooperation of CD4+ and CD8+ T cell CMI responses
| Observations: (2)
In mutant Listeria that lack lysteriolysin,
the oxidative burst in infected
macrophages, stimulated by CD4+ T cell
IFNg, will eradicate the infection.
Cooperation of CD4+ and CD8+ T cell CMI responses
In wild-type Listeria, where the bacteria
escape to the cytoplasm, the additional
lytic action by CD8+ CTLs is required
before the infection is eradicated.
28
```
Listeria monocytogenes
Gram+ rods, aerobic / facultatively anaerobic
Virulence factors
Clinical features
Treatment
EPIDEMIOLOGY (5)
```
Listeriolysin O
internalins
ActA-intracellular motility
growth at 4ºC
neonatal abscess,
meningitis
like-flu in adults
systemic disease in CMI- deficient persons
```
ampicillin or penicillin
− or + gentamicin
Increasingly:
plasmid-acquired
antibiotic resistance
```
```
immune compromised
neonates
elderly
pregnant women
contaminated food
```
29
```
Mycobacteria
characterizations (4)
```
Mycolic acids in cell wall
Gram+ weak staining: use acid-fast stain
or specific fluorescent detection
Facultative intracellular growth (in macrophages)
Obligate aerobe (growth in lung macrophages)
30
Koch identified Mycobacterium tuberculosis
| as cause of TB in 1882: (2)
• Humans are reservoir
• airborne transmission (as few as 10 cells
can result in infection)
31
Acid-fast stain
1. hot carbol fuchsin: acid fast cells, red
2. acid-alcohol (decolorizer): nonacid fast cells, blue
methylene blue (counter stain)
Mycobacteria can be subjected to Gram staining but this requires a
pre-treatment:
1. treat with alkaline-alcohol to extract lipid mycolic acids
2. do Gram stain: result Gram+
32
skipped
Structural mycobacterial cell wall components which are Virulence Factors
(4)
cord factor (glyco-lipid)
mycolic acid
mannose-cappde lipoarabinomanah
arabinogalatan
33
Mycobacteria Virulence Factors
Slow, cord-like growth
strongly correlates
with virulence.
34
Cord-like growth results from
adherence of cell surface
| lipid mycolic acids and glyco-lipids
35
Virulence Factors (2) M.tuberculosis and M.leprae
While many “virulence factors” are listed, their virulence results from the challenge that
they provide to the immune response (typically DTH: CD4+ T-cells + macrophages)
because
(in most cases) the disease is caused by the immune response,
NOT by the mycobacteria.
36
Facultative intracellular growth in alveolar and other macrophages:
inhibition of phago-lysosome fusion
37
CMI to Mycobacterium tuberculosis
TB granuloma surrounded by punctate nuclei
of lung tissue and inflammatory leukocytes.
Central area of necrosis where nuclei have
been destroyed.
Mycobacterium tuberculosis is a “life-long” pathogen:
once infected, you may be asymptomatic but never cured.
38
CMI to Mycobacterium tuberculosis
| Aerosol transmission
Effective CMI is capable of localizing and stopping infection by M.tuberculosis. Chronic TB is
typical.
39
CMI to Mycobacterium tuberculosis
| Exception:
young children under 5 years have a high risk for developing progressive TB due
to insufficient immune system development/activation.
40
CMI to Mycobacterium tuberculosis
OUTCOMES of untreated primary TB [results for non-immune-compromised patents]: (3)
* --% no disease
* --% clinical TB (2% pulmonary + 3% extrathoracic + 1% both)
* --% progressive systemic disease and death.
* 91% no disease
* 6% clinical TB (2% pulmonary + 3% extrathoracic + 1% both)
* 3% progressive systemic disease and death.
41
CMI to Mycobacterium tuberculosis
However, acute (‘open’) TB [also known as “secondary tuberculosis” or in older terms “--- ---” caused by “--- ---” of prior infection - while rare (life-time risk is assessed as <12% for carriers, or less) it is VERY contagious!
Isolation of acute TB cases is mandatory.
Endogenous reactivation is stimulated by stress, malnutrition and HIV
galloping consumption
| endogenous reactivation
42
CMI to Mycobacterium tuberculosis
| Actually, the “disease” (except for the infection risk of “Open TB”) arises from
tissue destruction
by our immune defenses and not by damage caused by the bacterial infection.
The repeated attempts to remove foci of infection by lung macrophages cause the granulomatous
lung tissue that impairs lung function.
Breathing impairment in TB is not due to tuberculosis bacilli but by the macrophage-induced tissue
destruction
43
Mantoux Reaction
```
A positive tuberculin test to
subdermal PPD (processed
protein derivative of the cell
wall of the opportunistic
intracellular pathogen
Mycobacterial tuberculosis).
```
44
Mantoux Reaction
Positive test: >-- mm redness
Strongly positive: >--mm red
10
| 20
45
Mantoux Reaction
Vaccination
Exposure to living attenuated mycobacterium, known as Bacille Calmette-Guérin (BCG), a
derivative of M.bovis (which may be identical to M.tuberculosis based on whole genome sequencing): (3)
• little virulence in humans (but infectious in immune-compromised persons)
• some protective immunity (when given to young children)
• BCG vaccination is discouraged in USA because it gives a positive tuberculin test, thus removing
an important diagnostic screening tool. (And M.bovis causes disease in immune-compromised persons.)
46
Mycobacterium leprae: diverse CMI responses
| TH1-response
macrophages kill nerves;
| macules and plaques without sensation
47
Mycobacterium leprae: diverse CMI responses
| Loss of CMI
(or TH2-response
CTL lysis and
loss of tissue)
(including nerves)
48
Tuberculoid vs Lepromatous Leprosy
| Multidrug therapy:
Dapsone + rifampin + clofazimine
| Rising resistance is becoming a problem.
49
```
Mycobacterium
Gram+ rods (branched), strict aerobic, mycobacteria
M.species
M.tuberculosis
(obligate aerobic)
(doubling time: 1 d)
```
Virulence factors (1)
Clinical features (1)
Treatment (2)
Epidemiology (3)
Ability to survive
and live in lung
macrophages
pulmonary (and
extrapulmonary)
tuberculosis
```
multidrug therapy:
isoniazid (INH)º +
rifampin +
ethambutol +
pyrazinamide *
6-12 months
```
```
Aerosol
(person-to-person)
All ages
Highest risk if
immune
compromised (HIV)
```
50
```
Mycobacterium
Gram+ rods (branched), strict aerobic, mycobacteria
M.species
M.leprae
(doubling time: 12 d)
```
Virulence factors (1)
Clinical features (1)
Treatment (2)
Epidemiology (1)
Ability to survive
and live in
macrophages
tuberculoid-tolepramatous
leprosy
```
multidrug therapy:
dapsone +
rifampicin + (for
lepramatous form)
clofazimine
2+ years
```
Close physical
contact
51
All pathogenic mycobacterial species have (very) --- growth rates
slow
52
```
Nocardia
characterization (2)
```
• Gram+ (poor staining)
• mycolic acid in cell wall: “partially acid-fast”
(Test to distinguish Nocardia from fungal look-alikes)
53
Nocardia
| VF
Opportunistic pathogen
| in immuno-compromised patients
54
```
Nocardia
Gram+ rods (branched), mycobacteria
Virulence factors
Clinical features
Treatment
Epidemiology
i
```
ntracellular survival +
growth
catalase
superoxide dismutase
bronchopulmonary
cutaneous infections
brain abscesses
sulfonamides
amikacin, carbapenems
or cephalosporins
opportunistic pathogen
(if pulmonary disease or
T deficiency)
55
Treponema pallidum
| characteristics (3)
Gram− spirochete but no LPS
flagella (3/pole) in an axial filament (between inner &outer membrane)
fragile (only survive transmission without exposure):
sexual and congenital (placental) transmission in body fluids and
mucous membranes
56
Treponema pallidum
| VF
host response causes disease
| symptoms
57
Syphilis
| A new-world ®
old-world
| disease thanks to Columbus
58
Syphilis
| Transmission: (2)
• sexual (human reservoir)
• congenital (spirochete
crosses placenta: late lethality)
59
Syphilis
| Stages: (3)
```
1.local: hard chancre/ulcer at
site of infection; infectious
2.disseminated: rash, aches;
mucous membrane lesions
(“the great imitator”);
infectious
3.gummas; damage to blood
vessels, eyes, CNS;
insanity; not infectious
```
60
Primary syphilis:
2-6 weeks; chancre, which heals
| spontaneously, giving false sense of relief.
61
Asymptomatic period:
2-24 weeks
62
• Secondary syphilis:
2-6 weeks; 50% of primary
infections go on to secondary; symptoms typically
resolve spontaneously (but recurrence in 25% with 1 yr)
63
Microbe persists for -- of secondary infections, with --
| exhibiting tertiary syphilis
2/3
| 1/2
64
Tertiary syphilis:
diffuse, chronic inflammation
65
gummas –
These form in tertiary syphilis
granuloma lesion = inflammatory mass which can perforate, e.g. roof of
mouth or any other tissues
66
congenital syphilis
[completely preventable by penicillin treatment early in pregnancy!)
67
high lethality in-utero OR
| when initially born without symptoms:
high lethality typical of young children (e.g. 2 yrs old) with facial
and dental abnormalities like “Hutchinson’s incisors” and “mulberry molars”.
68
syphilis tx
penicillin for 1º and 2º infections, which contain actively growing spirochetes
No vaccine
69
Borrelia
| characteristics
Gram− spirochete
70
Lyme Disease: Borrelia burgdorferi
Ixodes scapularis Tick
The tick transmission cycle sustains the bacteria, B. burgdorferi, that cause Lyme
disease. Lyme disease risk is greatest in spring and summer, but can occur during all
four seasons. Nymphs, which feed in the late spring and early summer, are responsible
for transmitting the majority of infections to humans.
71
Lyme Disease: Borrelia burgdorferi
| transmission (2)
* ticks
| * reservoir: rodents, deer
72
Lyme Disease: Borrelia burgdorferi
| disease (3)
1. acute, local: fever
2. disseminated: nerve
paralysis (with heart
arrhythmia)(2-8 wks)
3. chronic: arthritis,
CNS paralysis (due
to persistent immune
response)(>6 months)
73
Lyme Disease: Borrelia burgdorferi
| vaccine
no effective vaccine
74
Lyme Disease: Borrelia burgdorferi
| rash
Erythema
migrans
rash
75
Relapsing Fever: Borrelia spp.
| VF
Relapsing fever due to effective
| immune response to antigenic variation
76
infection: relapsing fever, epidemic (louse born)
reservoir
vector
humans
body louse
B. recurrentis
77
infection: relapsing fever, epidemic (tick born)
reservoir
vector
rodents, soft shelled ticks
soft shelled tick
B. miyamotoi
78
```
Spirochetes
Species: Treponema pallidum
Virulence factors
Clinical features
Treatment
Epidemiology
```
adherence
hyaluronidase
coat
host response
Syphilis: 1º, 2º, 3º,
congenital
penicillin
sexual or
congenital
transmission
(human reservoir)
79
```
Spirochetes
Species: Borrelia sp.
Virulence factors
Clinical features
Treatment
Epidemiology
```
surface binding
proteins
antigenic variation
(relapsing fever)
```
Lyme disease:
erythema migrans
neurologic, cardiac,
rheumatic
Relapsing fever
```
penicillin
tetracyclines
ceftriaxone
Ticks, lice from
animal reservoir
80
```
Rickettsia
characteristics (3)
```
```
Gram−
obligate intracellular parasite
entry into endothelial cells, escape
vascular hemorrhages
(no laboratory culture)
```
81
Transmission of this zoonosis: (2)
* wood tick (including transovarian transmission from adult ticks into tick eggs)
* reservoir: wild rodents
82
Rocky Mountain spotted fever: CTL immune disease
| Disease: (3)
• rash of extremities, then trunk
• hemorrhagic lesions (with disseminated vascular
CTL lysis of endothelial cells) ► spots
• dissemination to heart, kidneys, etc ► shock, death
(mortality = 20-40% if no treatment)
83
Chlamydia trachomatis
| Agent of
chlamydia
The most frequent sexually transmitted infection (followed by
gonorrhea, AIDS and syphilis)
84
Chlamydia trachomatis (3)
Obligate intracellular parasite (no laboratory culture; “ATP”-parasite)
No “peptidoglycan” synthesis (although the bacterial cell wall looks ‘normal G−’)
Inflammatory cytokines released from infected cells cause disease
manifestations
85
Inflammatory cytokines released from infected cells cause disease
manifestations:
damaging cell-mediated immune response in various
| tissues.
86
Chlamydia trachomatis
| EB:
epithelial cell adhesion to microvilli ► RB in phagosomes (no fusion with
lysosomes) ► replication and division ► EB ► cell lysis / exocytosis
87
EB =
elementary body
| stable, infectious
88
RB =
reticulate body
(replicating, fragile,
non-infectious)
89
Chlamydial diseases caused by CMI responses
| 8 serotypes:
gonorrheal-like sexual disease
• Mucopurulent urethritis, cervicitis, salpingitis (fallopian tube
infection)
• mobility by adhesion to sperm (► epididymitis prostatitis in men)
• PID (pelvic inflammatory disease) ► scarring ► ectopic pregnancy
+ decreased fertility
90
Chlamydial diseases caused by CMI responses
| 3 serotypes:
lymphogranuloma venereum
91
Chlamydial diseases caused by CMI responses
| 4 serotypes:
trachoma (endemic chronic eye infection: blindness)
| ophthalmia neonatorum with conjunctivitis and pneumonia
92
Chlamydial diseases caused by CMI responses (2)
ü no immune protection
| ü reinfection: stronger CMI
93
C.pneumoniae strain causes
“walking pneumonia”
94
Mycoplasma pneumoniae
| characteristics (3)
non-Gram staining (no rigid cell wall: no effect of
penicillin or lysozyme); strong membrane (due to sterols)
no sterilization by filtration (0.45μm)
Mycoplasma species are smallest prokaryote (M.
genitalium 580,070 bp – 475 genes)
strict aerobe (preference for bronchial mucosa)
95
Mycoplasma pneumoniae
| Disease:
• atypical, mild pneumonia, the leading cause in schools, students,
and military: aerosol transmission in crowded conditions
96
Mycoplasma pneumoniae
| tx
no vaccination; fading protective immunity after recovery
97
pneumococcal Pneumonia
| tx
capsular vaccine available
98
klebsiella Pneumonia
| tx
no vaccine available
99
mycoplasmal Pneumonia
| tx
no vaccine available
100
Mycoplasma pneumonia is also known as “walking pneumonia” because
it is typically mild and without the need for hospitalization.
