mycobacteria Flashcards
mycobacteria gram
positive, weakly
mycobacteria acid of cell wall
mycolic acid
mycobacteria cell growth and O2 use
Facultative intracellular growth (in macrophages) Obligate aerobe (growth in lung macrophages)
reservoir/ transmission for mycobacteria
- Humans are reservoir
* airborne transmission (as few as 10 cells can result in infection)
growth rates of pathogenic mycobacteria
slow
Acid-fast stain
used with mycobacteria
use of hot carbol fucshin to adhere to mycolic acid, stains red
important components/ virulence factors of mycobacteria cell wall
mycolic acid
cord factor
arabinogalactan
lipoarabinomanan
mycolic acid and cord factor of cell wall
results in?
correlated with?
Cord-like growth results from adherence of cell surface lipid mycolic acids and glyco-lipids
Slow, cord-like growth strongly correlates with virulence.
Virulence of M.tuberculosis and M.leprae due to?
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.
Virulence Factors of M.tuberculosis and M.leprae
Facultative intracellular growth in macrophages mycosides sulfatides cord factor adenylate cyclase arabinogalactan/ lipoarabinomannan mycolic acid
CMI to Mycobacterium tuberculosis; granuloma
TB granuloma surrounded by punctate nuclei of lung tissue and inflammatory leukocytes.
Central area of necrosis where nuclei have been destroyed.
mycobacterium tuberculosis: life long?
Mycobacterium tuberculosis is a “life-long” pathogen: once infected, you may be asymptomatic but never cured
o Mycobacterium tuberculosis tranmission
aerosols
Effective CMI to M.tuberculosis capable of?
exception?
Effective CMI is capable of localizing and stopping infection by M.tuberculosis. Chronic TB is typical.
Exception: young children under 5 years have a high risk for developing progressive TB due to insufficient immune system development/activation.
OUTCOMES of untreated primary TB [results for non-immune-compromised patents]:
- 91% no disease
- 6% clinical TB (2% pulmonary + 3% extrathoracic + 1% both)
- 3% progressive systemic disease and death
secondary tuberculosis
reemergence after primary infection
However, acute (‘open’) TB [also known as “secondary tuberculosis” or in older terms “galloping consumption” caused by “endogenous reactivation” 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
tuberculosis disease/ symptoms arise from?
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)
Positive test: >10 mm redness
Strongly positive: >20mm red
Vaccination to mycobacterium
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):
• 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.)
TB opportunistic?
recent increase
overall decrease
opportunistic disease
HIV infections, with its Acquired Immune Deficiency Syndrome (AIDS),
has caused a recent increase.
Better living standards, with help of the BCG vaccine and antibiotic protocols, have
reduced TB death rates dramatically
main Treatment for TB
isoniazid: block mycolic acid synthesis
Mycobacterium leprae: diverse CMI responses
diversity of responses can determine prognosis
effective CMI: healthy
Th1 response: tuberculoid, macrophages kill nerves; macules and plaques without sensation, good prognosis, not contagious
Loss of CMI (or TH2-response, CTL lysis and loss of tissue, including nerves): lepromatous, bad prognosis/ highly contagious
Mycobacterium leprae intra or extracellular?
preferred target?
M.leprae is an obligate intracellular pathogen
Peripheral nerves are preferred target tissue for infection and cytolysis
Histology: tuberculoid vs lepramatous leprosy
more growth of cells in lepramatous leprosy
Tuberculoid plaque
Tuberculoid plaque: without sensation, resulting from macrophage action after TH1 cytokine (IFNg) activation
good prognosis
Lepromatous Leprosy
TH2 Leprosy:
• cytokine (IL4) activation of CTL tissue lysis
bad prognosis
leprosy treatments
Multidrug therapy: Dapsone + rifampin + clofazimine
Rising resistance is becoming a problem
TH1 (tuberculoid) vs TH2 (leprosy) M.leprae responses bacteria level? infectivity? T response? IgG? Ig level?
Tuberculoid granuloma • no or few bacteria • low infectivity • Ag-specific TH1 • no Ag-spec IgG • normal Ig level
Leprosy • many bacteria inside macrophages • high infectivity • extensive tissue damage • no T-response to Ag • sometimes Ag-spec IgG • hyper-Ig level
M.tuberculosis main virulence factor
Ability to survive and live in lung macrophages
M.tuberculosis clinical presentation
pulmonary (and
extrapulmonary)
tuberculosis
M.tuberculosis treatment/ length
multidrug therapy
6-12 months
M.tuberculosis epidemiology
Aerosol
(person-to-person) All ages
Highest risk if immune compromised (HIV)
M.leprae main virulence factor
survival in macrophages
M.leprae clinical presentation
tuberculoid-tolepramatous
leprosy
M.leprae treatment/length
mutli drug
2 years
m. leprae epidemiology
contact dependent
All pathogenic mycobacterial species growth rates
All pathogenic mycobacterial species have (very) slow growth rates
Nocardia gram
Gram+ (poor staining)
Nocardia acid fast
mycolic acid in cell wall: “partially acid-fast”
Test to distinguish Nocardia from fungal look-alikes
Nocardia as a pathogen
Opportunistic pathogen in immuno-compromised patients
Nocardia virulence factors
main action?
which spp?
Antiphagocytic Virulence Factors of strictly aerobic Nocardia sp
catalase superoxide dimutase cord factor prevent lysosomal acidification slow growth
Nocardia clinical presentation
bronchopulomanry
cutaneous infections
brain abcesses
