Exam 2 Lecture 13 Flashcards

Mycobacteria

1
Q

Many Mycobacteria are _____ organisms. They can be found in:

A

opportunistic; Water, soil, food (plumbing)

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2
Q

The most common species of Mycobacteria is:

A

M. tuberculosis

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3
Q

The genus Mycobacterium includes 2 ____ parasites, which are:

A

Obligate; M. tuberculosis and M. leprae

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4
Q

How do we organize mycobacterial human pathogens?

A

We organize them based on the diseases the cause (i.e. organized clinically)

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5
Q

What are the three categories of Mycobacterial human pathogens?

A
  1. Mycobacterium tuberculosis complex
  2. Mycobacterium leprae
  3. Nontuberculosis mycobacteria
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6
Q

Mycobacterium tuberculosis complex (definition and associated species)

A

species that cause tuberculosis; M. tuberculosis, M. bovis

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7
Q

Mycobacterium leprae causes:

A

Leprosy

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8
Q

Nontuberculosis mycobacteria (definition)

A

Any other mycobacterium that causes human disease (but not TB or leprosy)

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9
Q

____ ____ is an important determinant of mycobacterial disease presence and severity.

A

Host susceptibility (i.e. immune characteristics)

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10
Q

True or false: differences between strains of Mycobacteria are very important determinants of how sick the host will get and how severe the disease will be.

A

False (strain differences are much less important than host susceptibility)

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11
Q

Mycobacteria differ greatly from gram positive and gram negative species in that:

A

Their cell walls contain mycolic acids

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12
Q

Can you use a gram stain approach in Mycobacteria?

A

No, you use acid-fast staining

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13
Q

What is the acid-fast staining process?

A
  1. Stain with carbol fuschin
  2. Decolorize with acid-alcohol
  3. Counterstain with methylene blue
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14
Q

Mycobacteria are slow-growing and thus are ____. They can be divided further into two categories:

A

fastidious (also difficult to culture); slow-growing and fast growing

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15
Q

Mycobacteria produce distinct ____ ____ that may be used to speciate clinical isolates. However, it more useful to use ____ and ______ ____.

A

carotenoid pigments; PCR and biochemical tests

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16
Q

True or false: Mycobacteria are strict aerobes and lack anaerobic metabolic capacity.

A

True

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17
Q

Do Mycobacteria possess flagellae?

A

No, they are non-motile

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18
Q

2 factors that hinder diagnosis and lab study of Mycobacteria

A
  1. difficult to culture in vitro

2. difficult to manipulate genetically (due to lack of tools/gene knockdown)

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19
Q

Why does the slow-growing nature of Mycobacteria make them difficult to treat?

A
  1. may be less likely to respond to standard antibiotics

2. can develop resistance to single agents easily

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20
Q

What diseases can nontuberculosis mycobacteria cause?

A
  • pulmonary disease similar to TB
  • lymphadenitis
  • skin and soft tissue diseases
  • disseminated diseases
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21
Q

True or false: Mycobacteria stains strongly gram positive.

A

False; neither GP nor GN

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22
Q

Mycolic acids make up ____% of the cell wall and allows cells to be resistant to ____.

A

60; desiccation

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23
Q

Mycolic acids are anchored to the rest of the cell wall through _______.

A

Arabinogalactan

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24
Q

True or false: Mycobacteria do not contain peptidoglycan

A

False: they do, just small amount

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25
Q

Slow-growing mycobacteria grow ___ times slower than E.coli and forms visible colonies after _ ___.

A

40; 7 days

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26
Q

Fast-growing mycobacteria grow ___ times slower than E. coli and forms visible colonies ______.

A

20; before 7 days

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27
Q

Common bacterial densities in some infections are ____

A

10^9 - 10^11 cells/mL

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28
Q

What is the mutation rate in Mycobacteria that can confer antibiotic resistance per cell per division?

A

10^-8 mutations per cell per division

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29
Q

Mycobacterium tuberculosis currently infects ____ of all people worldwide.

A

1/4

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30
Q

True or false: there are ~5 million TB deaths per year worldwide currently.

A

False: ~1.5 million deaths

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31
Q

TB infections accelerated during:

A

Europe’s industrial revolution

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32
Q

What are the three conditions that TB thrives under?

A

Poverty, crowding, and malnutrition

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33
Q

Multidrug resistance remains a problem in places where:

A

access to care is limited

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34
Q

There is a concurrence of both ___ and ___ prevalence in the world.

A

TB and HIV

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35
Q

How does HIV/AIDS impact TB? (4 things)

A
  1. TB disease burden is highest in areas with endemic HIV
  2. HIV increases susceptibility to TB
  3. HIV impacts T cell-mediated immunity which may worsen TB outcomes
  4. AIDS increases susceptibility to nontuberculosis mycobacteria
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36
Q

True or false: the current COVID-19 pandemic threatens to reverse the progress made towards global TB targets

A

True

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37
Q

How has COVID-19 adversely impacted us? (5 things)

A
  1. access to care
  2. food distribution
  3. TB and HIV testing
  4. Treatment of TB and HIV
  5. Household income
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38
Q

True or false: the WHO has prioritized restoring TB testing and treatment after the pandemic is over.

A

False; during the pandemic, not after

39
Q

Primary TB is characterized by: (3 things)

A
  1. Often clinically quiescent
  2. Disseminated + dramatic disease can occur in immunocompromised patients
  3. In normal hosts, latency can occur
40
Q

Secondary TB is characterized by: (3 things)

A
  1. night sweats, fever, weight loss
  2. infectious cough
  3. can infect vertebrae and meninges (CNS)
41
Q

How is TB transmitted?

A

droplet nuclei that can penetrate the alveoli in the lung

42
Q

What characteristics of droplet nuclei are thought to be important for causing infection? (2 things)

A
  1. desiccate and shrink over time

2. they have to be very small, and just the right size to run through nares, pharynx, trachea, and into lungs

43
Q

Droplet nuclei are produced by:

A

Infected person via cough, talking, sneezing

44
Q

True or false: droplet nuclei often fall to the ground quickly due to gravity.

A

False: they can remain suspended in the air for hours

45
Q

TB transmission usually require ____ and ____ exposure for infection.

A

recurrent and prolonged

46
Q

After TB primary infection, M. tb enters the ____ and is ingested by _____ where M. tb can then replicate.

A

alveoli; macrophages

47
Q

When M. tb replicate in macrophages, this can ____ them and:

A

destroy; signal to other macrophages and T cells to come to the site of infection

48
Q

What is a granuloma and how is it formed?

A

A granuloma is essentially a ball of infection and inflammation as a result of M. tb infection. It is formed when M. tb is ingested by macrophages and signals more macrophages to the site of infection, creating a destructive cycle where more and more macrophages are infected.

49
Q

True or false: only when your immune response becomes effective, you start to develop symptoms

A

True

50
Q

Infected macrophages can disseminate via ____ to ___ ___ and beyond.

A

lymphatics to lymph nodes

51
Q

The immune response usually ____ the infection.

A

contains

52
Q

After primary TB infection, in immunocompetent hosts:

A

hypersensitivity/cellular immunity develop and infection is usually controlled

53
Q

Can immunocompetent hosts get reinfected after primary infection of TB?

A

Usually no, but reactivation can occur later

54
Q

After primary TB infection, immunocompromised hosts can:

A

get progressive and disseminated disease that does not control/contain the infection

55
Q

Primary TB infection is often progressive in these 2 age groups:

A

infants and elderly

56
Q

Reactivation of TB usually occurs within _ ___ and occurs in the:

A

2 years; apices of the lungs

57
Q

What is a common reason for TB reactivation?

A

HIV or cancer therapy, possibly due to immunosuppression

58
Q

What happens during TB reactivation?

A

granulomas open up, macrophages continue to kill and bacteria keep growing in cavities until granulomas eventually empty out infected junk through the infectious cough

59
Q

True or false: only humoral immunity seems to make a big difference in TB host response

A

False: cellular immunity

60
Q

There is …… immune response in early TB infection.

A

little to no

61
Q

Macrophages have multiple ___ receptors, such as:

A

Mtb; complement receptors

62
Q

True or false: Mtb can resist getting killed in acid phagolysosomes.

A

True

63
Q

__ _______ are critical for activating the immune response in TB.

A

CD4+ T-lymphocytes

64
Q

Hypersensitivity is usually experienced ___ after exposure.

A

3-8 weeks

65
Q

During TB hypersensitivity: (2 things)

A
  1. increased macrophage killing and control in normal host

2. formulation of granulomas that contain infection, can either heal or necrose/caseate

66
Q

What are 5 methods we can use to diagnose TB?

A
  1. microscopy
  2. culture
  3. PCR
  4. Skin test (PPD)
  5. IFN-gamma release tests
67
Q

The gold standard to diagnose TB is ____, but:

A

culture; but takes a long time (3-6 weeks)

68
Q

QuantiFERON Gold and T-spot are _____ ____ ____ and are much more ____.

A

IFN-gamma release tests; common

69
Q

It is important to use at least __ treatments to treat TB in order to:

A

3; create synergy and prevent antibiotic resistance to single agents

70
Q

If a patient has a known exposure of TB but has no identifiable disease, we treat them with:

A

INH only for chemoprophylaxis

71
Q

M. leprae was the ____ _____ identified as causing disease in humans and was discovered by ____ ___ ____.

A

first bacterium; Gerhard Armauer Hansen

72
Q

True or false: the ability to diagnose and treat leprosy quickly advanced soon after its discovery.

A

False- has only recently advanced

73
Q

Can we cultivate M. leprae in vitro?

A

No

74
Q

Leprosy hosts (3)

A
  1. humans and some other primates
  2. armadillos in the Americas (15% LA and TX)
  3. Eurasian red squirrels
75
Q

True or false: eurasian red squirrels and armadillos can transmit M. leprae easily.

A

False: role of either in transmission is unclear

76
Q

Those with leprosy have historically been:

A

ostracized and stigmatized

77
Q

Leprosy incubation time

A

2-10 years

78
Q

There are ____ types of leprosy manifestation, including:

A

several;

  1. tubercululoid or paucibacillary (low skin organism burden)
  2. Lepromatus or multibacillary (high skin organism burden)
  3. many other intermediate forms
79
Q

Tuberculoid/paucibacillary leprosy manifestation is characterized by: (3 things)

A
  1. often localized, single anesthetic skin lesions and rare thickened nerves
  2. spontaneous resolution can occur
  3. analagous to primary/latent/reactivated TB
80
Q

Lepromatous/multibacillary leprosy manifestation characteristics: (4 things)

A
  1. 10^15 cells per patient
  2. multiple skin lesions and thickened peripheral nerves, anesthesia, weakness
  3. spontaneous resolution does not occur
  4. analagous to systemic tuberculosis, where there is poor cell-mediated immune response
81
Q

Leprosy transmission is thought to occur via ____ ____, and exposure to ____ and/or ____ may be important.

A

aerosol route; animals; soil

82
Q

For leprosy transmission it is thought that ____, ___ exposure is important, but it is not as important as _____ _____.

A

long-term, close; genetic predisposition

83
Q

True or false: we can easily diagnose leprosy by simply cultivating in vitro.

A

False: this is complicated, we currently cannot culture in vitro

84
Q

Usually, diagnosis of leprosy is often made by ____ _____. Some symptoms that we can look for are: (3)

A

clinical suspicion; localized weakness and anesthesia, skin lesions, thickened nerves

85
Q

Leprosy treatment included ___ as a monotherapy for a short time, but _____ occurred very quickly.

A

dapsone; resistance

86
Q

The standard to treating leprosy is ___ ____. We use ____, ____, and _____.

A

multidrug therapy; dapsone, Rifampin, Clofazimine

87
Q

How long does it take for infectiousness to be lost in leprosy if given multidrug treatment?

A

within 3 days (very high efficacy)

88
Q

M. bovis

A

can cause tuberculosis

89
Q

M. kansasii and M. avium-intracellulare

A

can cause tuberculosis-like respiratory disease

90
Q

M. scrofulaceum

A

lymphadenitis (“scrofula”)

91
Q

M. fortuitum, marinum, ulcerans

A

skin and soft tissue infections

92
Q

M. abscessus, M. chelonae

A

opportunistic pulmonary infections

93
Q

True or false: M. tuberculosis is among the most important human pathogens of all time.

A

True