Exam 2 Lecture 13 Flashcards
Mycobacteria
Many Mycobacteria are _____ organisms. They can be found in:
opportunistic; Water, soil, food (plumbing)
The most common species of Mycobacteria is:
M. tuberculosis
The genus Mycobacterium includes 2 ____ parasites, which are:
Obligate; M. tuberculosis and M. leprae
How do we organize mycobacterial human pathogens?
We organize them based on the diseases the cause (i.e. organized clinically)
What are the three categories of Mycobacterial human pathogens?
- Mycobacterium tuberculosis complex
- Mycobacterium leprae
- Nontuberculosis mycobacteria
Mycobacterium tuberculosis complex (definition and associated species)
species that cause tuberculosis; M. tuberculosis, M. bovis
Mycobacterium leprae causes:
Leprosy
Nontuberculosis mycobacteria (definition)
Any other mycobacterium that causes human disease (but not TB or leprosy)
____ ____ is an important determinant of mycobacterial disease presence and severity.
Host susceptibility (i.e. immune characteristics)
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.
False (strain differences are much less important than host susceptibility)
Mycobacteria differ greatly from gram positive and gram negative species in that:
Their cell walls contain mycolic acids
Can you use a gram stain approach in Mycobacteria?
No, you use acid-fast staining
What is the acid-fast staining process?
- Stain with carbol fuschin
- Decolorize with acid-alcohol
- Counterstain with methylene blue
Mycobacteria are slow-growing and thus are ____. They can be divided further into two categories:
fastidious (also difficult to culture); slow-growing and fast growing
Mycobacteria produce distinct ____ ____ that may be used to speciate clinical isolates. However, it more useful to use ____ and ______ ____.
carotenoid pigments; PCR and biochemical tests
True or false: Mycobacteria are strict aerobes and lack anaerobic metabolic capacity.
True
Do Mycobacteria possess flagellae?
No, they are non-motile
2 factors that hinder diagnosis and lab study of Mycobacteria
- difficult to culture in vitro
2. difficult to manipulate genetically (due to lack of tools/gene knockdown)
Why does the slow-growing nature of Mycobacteria make them difficult to treat?
- may be less likely to respond to standard antibiotics
2. can develop resistance to single agents easily
What diseases can nontuberculosis mycobacteria cause?
- pulmonary disease similar to TB
- lymphadenitis
- skin and soft tissue diseases
- disseminated diseases
True or false: Mycobacteria stains strongly gram positive.
False; neither GP nor GN
Mycolic acids make up ____% of the cell wall and allows cells to be resistant to ____.
60; desiccation
Mycolic acids are anchored to the rest of the cell wall through _______.
Arabinogalactan
True or false: Mycobacteria do not contain peptidoglycan
False: they do, just small amount
Slow-growing mycobacteria grow ___ times slower than E.coli and forms visible colonies after _ ___.
40; 7 days
Fast-growing mycobacteria grow ___ times slower than E. coli and forms visible colonies ______.
20; before 7 days
Common bacterial densities in some infections are ____
10^9 - 10^11 cells/mL
What is the mutation rate in Mycobacteria that can confer antibiotic resistance per cell per division?
10^-8 mutations per cell per division
Mycobacterium tuberculosis currently infects ____ of all people worldwide.
1/4
True or false: there are ~5 million TB deaths per year worldwide currently.
False: ~1.5 million deaths
TB infections accelerated during:
Europe’s industrial revolution
What are the three conditions that TB thrives under?
Poverty, crowding, and malnutrition
Multidrug resistance remains a problem in places where:
access to care is limited
There is a concurrence of both ___ and ___ prevalence in the world.
TB and HIV
How does HIV/AIDS impact TB? (4 things)
- TB disease burden is highest in areas with endemic HIV
- HIV increases susceptibility to TB
- HIV impacts T cell-mediated immunity which may worsen TB outcomes
- AIDS increases susceptibility to nontuberculosis mycobacteria
True or false: the current COVID-19 pandemic threatens to reverse the progress made towards global TB targets
True
How has COVID-19 adversely impacted us? (5 things)
- access to care
- food distribution
- TB and HIV testing
- Treatment of TB and HIV
- Household income
True or false: the WHO has prioritized restoring TB testing and treatment after the pandemic is over.
False; during the pandemic, not after
Primary TB is characterized by: (3 things)
- Often clinically quiescent
- Disseminated + dramatic disease can occur in immunocompromised patients
- In normal hosts, latency can occur
Secondary TB is characterized by: (3 things)
- night sweats, fever, weight loss
- infectious cough
- can infect vertebrae and meninges (CNS)
How is TB transmitted?
droplet nuclei that can penetrate the alveoli in the lung
What characteristics of droplet nuclei are thought to be important for causing infection? (2 things)
- 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
Droplet nuclei are produced by:
Infected person via cough, talking, sneezing
True or false: droplet nuclei often fall to the ground quickly due to gravity.
False: they can remain suspended in the air for hours
TB transmission usually require ____ and ____ exposure for infection.
recurrent and prolonged
After TB primary infection, M. tb enters the ____ and is ingested by _____ where M. tb can then replicate.
alveoli; macrophages
When M. tb replicate in macrophages, this can ____ them and:
destroy; signal to other macrophages and T cells to come to the site of infection
What is a granuloma and how is it formed?
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.
True or false: only when your immune response becomes effective, you start to develop symptoms
True
Infected macrophages can disseminate via ____ to ___ ___ and beyond.
lymphatics to lymph nodes
The immune response usually ____ the infection.
contains
After primary TB infection, in immunocompetent hosts:
hypersensitivity/cellular immunity develop and infection is usually controlled
Can immunocompetent hosts get reinfected after primary infection of TB?
Usually no, but reactivation can occur later
After primary TB infection, immunocompromised hosts can:
get progressive and disseminated disease that does not control/contain the infection
Primary TB infection is often progressive in these 2 age groups:
infants and elderly
Reactivation of TB usually occurs within _ ___ and occurs in the:
2 years; apices of the lungs
What is a common reason for TB reactivation?
HIV or cancer therapy, possibly due to immunosuppression
What happens during TB reactivation?
granulomas open up, macrophages continue to kill and bacteria keep growing in cavities until granulomas eventually empty out infected junk through the infectious cough
True or false: only humoral immunity seems to make a big difference in TB host response
False: cellular immunity
There is …… immune response in early TB infection.
little to no
Macrophages have multiple ___ receptors, such as:
Mtb; complement receptors
True or false: Mtb can resist getting killed in acid phagolysosomes.
True
__ _______ are critical for activating the immune response in TB.
CD4+ T-lymphocytes
Hypersensitivity is usually experienced ___ after exposure.
3-8 weeks
During TB hypersensitivity: (2 things)
- increased macrophage killing and control in normal host
2. formulation of granulomas that contain infection, can either heal or necrose/caseate
What are 5 methods we can use to diagnose TB?
- microscopy
- culture
- PCR
- Skin test (PPD)
- IFN-gamma release tests
The gold standard to diagnose TB is ____, but:
culture; but takes a long time (3-6 weeks)
QuantiFERON Gold and T-spot are _____ ____ ____ and are much more ____.
IFN-gamma release tests; common
It is important to use at least __ treatments to treat TB in order to:
3; create synergy and prevent antibiotic resistance to single agents
If a patient has a known exposure of TB but has no identifiable disease, we treat them with:
INH only for chemoprophylaxis
M. leprae was the ____ _____ identified as causing disease in humans and was discovered by ____ ___ ____.
first bacterium; Gerhard Armauer Hansen
True or false: the ability to diagnose and treat leprosy quickly advanced soon after its discovery.
False- has only recently advanced
Can we cultivate M. leprae in vitro?
No
Leprosy hosts (3)
- humans and some other primates
- armadillos in the Americas (15% LA and TX)
- Eurasian red squirrels
True or false: eurasian red squirrels and armadillos can transmit M. leprae easily.
False: role of either in transmission is unclear
Those with leprosy have historically been:
ostracized and stigmatized
Leprosy incubation time
2-10 years
There are ____ types of leprosy manifestation, including:
several;
- tubercululoid or paucibacillary (low skin organism burden)
- Lepromatus or multibacillary (high skin organism burden)
- many other intermediate forms
Tuberculoid/paucibacillary leprosy manifestation is characterized by: (3 things)
- often localized, single anesthetic skin lesions and rare thickened nerves
- spontaneous resolution can occur
- analagous to primary/latent/reactivated TB
Lepromatous/multibacillary leprosy manifestation characteristics: (4 things)
- 10^15 cells per patient
- multiple skin lesions and thickened peripheral nerves, anesthesia, weakness
- spontaneous resolution does not occur
- analagous to systemic tuberculosis, where there is poor cell-mediated immune response
Leprosy transmission is thought to occur via ____ ____, and exposure to ____ and/or ____ may be important.
aerosol route; animals; soil
For leprosy transmission it is thought that ____, ___ exposure is important, but it is not as important as _____ _____.
long-term, close; genetic predisposition
True or false: we can easily diagnose leprosy by simply cultivating in vitro.
False: this is complicated, we currently cannot culture in vitro
Usually, diagnosis of leprosy is often made by ____ _____. Some symptoms that we can look for are: (3)
clinical suspicion; localized weakness and anesthesia, skin lesions, thickened nerves
Leprosy treatment included ___ as a monotherapy for a short time, but _____ occurred very quickly.
dapsone; resistance
The standard to treating leprosy is ___ ____. We use ____, ____, and _____.
multidrug therapy; dapsone, Rifampin, Clofazimine
How long does it take for infectiousness to be lost in leprosy if given multidrug treatment?
within 3 days (very high efficacy)
M. bovis
can cause tuberculosis
M. kansasii and M. avium-intracellulare
can cause tuberculosis-like respiratory disease
M. scrofulaceum
lymphadenitis (“scrofula”)
M. fortuitum, marinum, ulcerans
skin and soft tissue infections
M. abscessus, M. chelonae
opportunistic pulmonary infections
True or false: M. tuberculosis is among the most important human pathogens of all time.
True
