3.21 Flashcards
Yersenia pestis, cause of plague
characterization
Black death
Gram−
Transmission of plague (3)
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
Francisella tularensis
characterization (2)
Gram−
opportunistic zoonosis
(birds, rabbits, tick bites) (bioterrorism)
Francisella tularensis
Virulence Factors: (1)
Ø intracellular growth in macrophages
(prevents phagolysosome fusion) bacteremia
Francisella tularensis
Diseases: rabbit fever, tick fever (2)
• ulceroglandular and
oculoglandular tularemia
• pulmonary tularemia
Brucella characteriztion (2)
Gram−
opportunistic zoonosis by B.melitensis (or bioterrorism)
undulant fever (brucellosis, “bangs disease”
systemic bacteremia starting from infected lymph nodes
skipped
undulant fever
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
Haemophilus influenzae
characterization (2)
Gram−
frequently part of oral flora (carrier rate up to 80%)
6 O-antigen serotypes: a – f: type b is most virulent
Haemophilus influenzae
Virulence Factors:
capsule b
Haemophilus influenzaem
Conjugated vaccine
against capsule b polysaccharides creates protective IgG, preventing systemic infections Vaccine does not protect against other encapsulated strains and unencapsulated strains
Haemophilus influenzae type b infections
cases per year before immunization
decrease after
20,000
99.7%
before the availability of conjugate vaccines in late 1987 H. influenzae type b was the most common cause of bacterial meningitis in
preschool children
Without vaccination: systemic diseases
in children) by encapsulated strains: (2
- meningitis
* septicemia, cellulitis, epiglottitis
Haemophilus influenzae Gram- rods, aerobic / facultatively anaerobic Virulence factors Clinical features Treatment EPIDEMIOLOGY (2)
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
Legionella pneumophila
characterization (4)
Gram−
facultatively intracellular
Growth up to 46C
Relatively resistant to chlorine and other biocides
facultatively intracellular (prevents endosome-lysosome fusion; autophagosome-like uptake)
Lives and proliferates in the vacuoles of amoebas and
in the endoplasmic reticulum of macrophages
Legionnaires disease: how was it disovered
infected roof A/C
Legionnaire’s disease
Virulence Factors:
Ø intracellular growth in alveolar macrophages
no phagolysosomal fusion
Legionnaire’s disease
Transmission:
aerosol from water sources (living inside amoeba)
No human-to-human transmission
Legionnaire’s disease
severe pneumonia, necrotic abscesses
especially in immune-compromised and elderly; mortality 20%
Listeria monocytogenes (6)
• 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)
— is rare (2500 cases/yr)
But exposure is common (10%
asymptomatic carriers)
Listeriosis
Listeria monocytogenes
VF
listeriolysin O
listeriolysin O
pore-forming toxin (phagosome escape)
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
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.
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
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)
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)
Acid-fast stain
- hot carbol fuchsin: acid fast cells, red
- 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+
skipped
Structural mycobacterial cell wall components which are Virulence Factors
(4)
cord factor (glyco-lipid)
mycolic acid
mannose-cappde lipoarabinomanah
arabinogalatan
Mycobacteria Virulence Factors
Slow, cord-like growth
strongly correlates
with virulence.
Cord-like growth results from
adherence of cell surface
lipid mycolic acids and glyco-lipids
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.
Facultative intracellular growth in alveolar and other macrophages:
inhibition of phago-lysosome fusion
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.
CMI to Mycobacterium tuberculosis
Aerosol transmission
Effective CMI is capable of localizing and stopping infection by M.tuberculosis. Chronic TB is
typical.
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.
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.
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
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
Mantoux Reaction
A positive tuberculin test to subdermal PPD (processed protein derivative of the cell wall of the opportunistic intracellular pathogen Mycobacterial tuberculosis).
Mantoux Reaction
Positive test: >– mm redness
Strongly positive: >–mm red
10
20
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.)
Mycobacterium leprae: diverse CMI responses
TH1-response
macrophages kill nerves;
macules and plaques without sensation
Mycobacterium leprae: diverse CMI responses
Loss of CMI
(or TH2-response
CTL lysis and
loss of tissue)
(including nerves)
Tuberculoid vs Lepromatous Leprosy
Multidrug therapy:
Dapsone + rifampin + clofazimine
Rising resistance is becoming a problem.
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)
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
All pathogenic mycobacterial species have (very) — growth rates
slow
Nocardia characterization (2)
• Gram+ (poor staining)
• mycolic acid in cell wall: “partially acid-fast”
(Test to distinguish Nocardia from fungal look-alikes)
Nocardia
VF
Opportunistic pathogen
in immuno-compromised patients
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)
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
Treponema pallidum
VF
host response causes disease
symptoms
Syphilis
A new-world ®
old-world
disease thanks to Columbus
Syphilis
Transmission: (2)
• sexual (human reservoir)
• congenital (spirochete
crosses placenta: late lethality)
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
Primary syphilis:
2-6 weeks; chancre, which heals
spontaneously, giving false sense of relief.
Asymptomatic period:
2-24 weeks
• Secondary syphilis:
2-6 weeks; 50% of primary
infections go on to secondary; symptoms typically
resolve spontaneously (but recurrence in 25% with 1 yr)
Microbe persists for – of secondary infections, with –
exhibiting tertiary syphilis
2/3
1/2
Tertiary syphilis:
diffuse, chronic inflammation
gummas –
These form in tertiary syphilis
granuloma lesion = inflammatory mass which can perforate, e.g. roof of
mouth or any other tissues
congenital syphilis
[completely preventable by penicillin treatment early in pregnancy!)
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”.
syphilis tx
penicillin for 1º and 2º infections, which contain actively growing spirochetes
No vaccine
Borrelia
characteristics
Gram− spirochete
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.
Lyme Disease: Borrelia burgdorferi
transmission (2)
- ticks
* reservoir: rodents, deer
Lyme Disease: Borrelia burgdorferi
disease (3)
- acute, local: fever
- disseminated: nerve
paralysis (with heart
arrhythmia)(2-8 wks) - chronic: arthritis,
CNS paralysis (due
to persistent immune
response)(>6 months)
Lyme Disease: Borrelia burgdorferi
vaccine
no effective vaccine
Lyme Disease: Borrelia burgdorferi
rash
Erythema
migrans
rash
Relapsing Fever: Borrelia spp.
VF
Relapsing fever due to effective
immune response to antigenic variation
infection: relapsing fever, epidemic (louse born)
reservoir
vector
humans
body louse
B. recurrentis
infection: relapsing fever, epidemic (tick born)
reservoir
vector
rodents, soft shelled ticks
soft shelled tick
B. miyamotoi
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)
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
Rickettsia characteristics (3)
Gram− obligate intracellular parasite entry into endothelial cells, escape vascular hemorrhages (no laboratory culture)
Transmission of this zoonosis: (2)
- wood tick (including transovarian transmission from adult ticks into tick eggs)
- reservoir: wild rodents
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)
Chlamydia trachomatis
Agent of
chlamydia
The most frequent sexually transmitted infection (followed by
gonorrhea, AIDS and syphilis)
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
Inflammatory cytokines released from infected cells cause disease
manifestations:
damaging cell-mediated immune response in various
tissues.
Chlamydia trachomatis
EB:
epithelial cell adhesion to microvilli ► RB in phagosomes (no fusion with
lysosomes) ► replication and division ► EB ► cell lysis / exocytosis
EB =
elementary body
stable, infectious
RB =
reticulate body
(replicating, fragile,
non-infectious)
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
Chlamydial diseases caused by CMI responses
3 serotypes:
lymphogranuloma venereum
Chlamydial diseases caused by CMI responses
4 serotypes:
trachoma (endemic chronic eye infection: blindness)
ophthalmia neonatorum with conjunctivitis and pneumonia
Chlamydial diseases caused by CMI responses (2)
ü no immune protection
ü reinfection: stronger CMI
C.pneumoniae strain causes
“walking pneumonia”
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)
Mycoplasma pneumoniae
Disease:
• atypical, mild pneumonia, the leading cause in schools, students,
and military: aerosol transmission in crowded conditions
Mycoplasma pneumoniae
tx
no vaccination; fading protective immunity after recovery
pneumococcal Pneumonia
tx
capsular vaccine available
klebsiella Pneumonia
tx
no vaccine available
mycoplasmal Pneumonia
tx
no vaccine available
Mycoplasma pneumonia is also known as “walking pneumonia” because
it is typically mild and without the need for hospitalization.
