Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IP > Mycobacterium Tuberculosis > Flashcards

Mycobacterium Tuberculosis Flashcards

1
Q

What causes TB? Symptoms?

A
  • Mycobacterium Tuberculosis
  • presents as chronic pneumonia, other organs can be infected
  • insidious onset: creep up
  • fatigue, cough, weight loss, weakness, night sweats and fever, not distinct or specific
  • sputum may be scant, or bloody and purulent
  • need TB test and chest X-ray to diagnose disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Places with highest incidence of TB?

A
  • sub saharan Africa, Eastern Europe, South East Asia
  • 9 million developed active disease in 2013
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

In the US, who is mostly affected by TB?

A
  • elderly malnourished men
  • African americans, native americans, native alaskans
  • HIV+, malnourished, alcoholics, patients with diabetes mellitus, Hodgkin Lymphoma, chronic lung disease, renal failure, immunosuppressed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Properties of TB?

A
  • humans are only natural reservoir- causes more deaths than any single microbe
  • obligate aerobe- predilection for growing in highly oxygenated tissues
  • can grow inside and outside macrophages (facultative intracellular pathogen)
  • slow growth rate- generation 18 hours, clinical specimens held for 6-8 weeks before recorded as negative
  • growth pattern showing cording, strings
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Stain of TB?

A
  • Acid fast bacillus, stains weakly Gram+
  • acid fast retains stains even when treated with a mix of acid and alcohol
  • hard to stain, hard to decolorize
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cell wall characteristics of TB? (slide 14)

A
  • cell wall unique to proks, very complex
  • thick wall of peptidoglycan, have LTA like molecule
  • rich in waxes and lipids (60%):
  • mycolic acid (C78-C90, long chain fatty acids)
  • pthiocerol dimycocerosate required for lung pathogenesis
  • cell wall accounts for:
  • acid fastness
  • slow growth
  • resistance to drying, disinfectants, acids and alkalis
  • resistance to antibiotics- trouble getting through wax coat
  • resistance to phagocytic killing
  • Purified Protein Derivatives (PPD):
  • transport and porin proteins throughout cell wall
  • when combined with waxes stimulate patients cell immune response (delayed hypersensitivity)
  • TB test
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

TB resistance to antibiotics?

A
  • multi drug resistant (MDR) strains:
  • resistant to Isoniazid (isonicotinic acid hydrazine, INH) and other anti TB drugs
  • INH resistance is due to mutation in a gene for mycolic acid synthesis and a gene for catalase peroxidase (enzyme required to activate INH)
  • extensively drug resistant (XDR) strains:
  • MDR TB are resistant to fluoroquinolone and at least one second line drug
  • potentially untreatable
  • HIV+ patients often are at risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Transmission of TB? (slide 18)

A
  • person to person by respiratory aerosols produced by coughing (3 bacilli/droplet)
  • if person is around a person infected, they will most likely become infected by a cough
  • when bacilli reach lungs they are ingested and grow inside and outside of non activated or activated macrophages and dendritic cells (inhibit phagosome fusing with lysosome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Process of TB bacteria proliferating in macrophage? (slide 19)

A
  1. mycobacteria infect non activated macrophage
  2. proliferate unchecked
  3. macrophage presents antigen to T cell in lymph nodes
  4. macrophage secretes IL-12
  5. T cell differentiates into TH-1 cells and secrete IFN-gamma (T helper cells in lymph node and lung)
  6. Macrophage is activated (TNF alpha)
  7. Granuloma in some cases see pic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where does Mtb grow? (slide 20)

A

inside and outside of inactive and active macrophages

  • cells fuse together
  • apoptosis can help spread the bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Anatomy of a TB granuloma? (slide 20)

A
  • middle: alveolar macrophages, epithelioid cells, giant cells with intracellular Mtb
  • periphery: macrophages, CD4 and CD8 T cells, B cells, NK cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What conditions can Mtb survive while in the macrophage? (slide 22)

A

-survives NO, decrease in pH and H2O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What initiates the immune response to Mtb?

A

-initiated by recognition of Mtb MAMPs (microbe associated molecular patterns) by PRRs (TLR2, TLR4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What cytokines are important to pathogenesis of Mtb?

A
  • IL-12
  • IFN-gamma
  • TNF-alpha
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens during the earliest stages of infection of Mtb?

A
  • less than 3 weeks
  • Mtb inhibit maturation of phagosome and formation of phagolysosome and replicate in the vesicles and cytoplasm of inactive alveolar macrophages and dendritic cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

IFN-gamma effects?

A
  • activates macrophages, leads to maturation and activation of phagolysosomes
  • stimulates production of of nitric oxide (NO), which combined with other ROS limits Mtb growth
  • stimulates autophagy destruction of damaged organelles and some intracellular Mtb (may facilitate spread of bacteria)
17
Q

What leads to granuloma and caseous necrosis?

A
  • the immune response is trying to fight the bacteria, which leads to destruction of tissue and granulomas
  • IFN-gamma activates macrophages to differentiate into epithelioid histiocytes that aggregate to form granulomas, some may fuse to form giant cells
  • activated macrophages secrete TNF alpha and chemokine to recruit more monocytes
  • infection is halted in some, progresses in older or immunosuppressed patients
  • ongoing immune response leads to caseating necrosis
18
Q

What could prevent further spread?

A

formation of nodular inflammation

19
Q

What defects lead patients to increased risk of Mtb infections?

A
  • patients with defects in TNF-alpha or IFN-gamma
  • if patient is undergoing therapy that inhibits these things
20
Q

What mediates immunity?

A
  • mediated by T helper cells which stimulate macrophages to kill bacteria
  • immune response leads to tissue destruction
  • reactivation of infection or re-exposure (secondary response) leads to a rapid immune response but increased tissue necrosis
21
Q

Primary TB? outcomes?

A
  • infection of a non immune host (initial exposure to Mtb)
  • possible outcomes:
  • healing by fibrosis (asymptomatic)
  • progressive lung disease (within 2 years), lesion in lower part of lung
  • Bacteremia (bacteria in blood) and Miliary TB (small, many granulomas in different tissues)
  • Hematogenous dissemination with no immediate disease but risk of reactivation later in life (LTBI) when immunosuppressed
  • granulomas may contain viable Mtb for years
  • associated with lymphohematogenous spread through body and lung apices
  • prior to development of immune response, organisms grow uninhibited in lungs and other sites
22
Q

Primary infection? chest X-ray?

A
  • Ghon complex- lung inflammation (granuloma) associated with a granuloma in a draining hilar lymph node
  • xray shows some fibrosis (in children)
23
Q

Progressive Primary TB?

A
  • caseuous material released into bronchioles with cavitation
  • tissue destruction and erosion of bronchiole arteries coughing up blood
  • seeding of TB into lymphatics and blood stream granulomas in liver, spell, kidneys, bones, meninges, skin (Miliary TB)
  • young children (5 years old) are at risk for Miliary TB
24
Q

Complications of Progressive TB?

A
  • overall granulomas have space occupying effects and cause tissue destruction
  • Miliary TB- seeding of Mtb to distant organs with development of foci in the meninge, urogenital tract, peritoneum, skin, bone, usually occurs in immune compromised individuals (HIV)
  • lung- chronic pneumonitis
  • brain- meningitis, seizures
  • adrenal gland- adrenal failure (Addisons disease)
  • bone- bone fractures (Potts disease)
25
Q

Secondary TB?

A
  • occurs in a host who has developed immunity to Mtb
  • cavity usually in upper lobes of lungs, later on
  • reactivation of a latent primary infection usually when host resistance is weakened
  • patient re-infected in an area endemic for TB
  • granulomas cavitation occurs more readily -> decay into structure-less mass of cell debris that spill thousands of viable Mtb -> extra pulmonary manifestations (other tissues)
26
Q

Summary of clinical infection? (slide 36)

A

see pic

27
Q

Do circulating antibodies play a role in resistance to TB?

A
  • no
  • resistance is mediated by cell mediated immunity mainly CD4+ T cells and macrophages
  • patients with aids or mutations in IFN receptor gene are at increased risk for severe TB
28
Q

Tuberculin skin test? (slide 40)

A
  • useful for diagnosis and control of TB
  • based on fact that individuals infected with TB have T cells that mediate a Type IV hypersensitivity response to the proteins of the organism (PPD, purified protein derivative)
  • positive reaction is indicated by a red, indurated area at site of inoculation (cell mediated immunity), depends on clinical picture
  • positive test identifies a recent or past TB infection but not an active disease
  • diameter indicates positive result varies depending on status of individual (small diameter is positive for HIV patients), large diameter for young and healthy needed for positive result
29
Q

In vitro IFN-gamma Release Assay (IGRA)?

A
  • patients previously infected with Mtb will have sensitized T cells in their blood that will make IFN-gamma when exposed to Mtb antigen
  • patients don’t have to return to office for analysis of results
  • Mtb specific antigen used, so result not affected by BCG immunization
  • used to make sure not a false positive
30
Q

Treatment of active TB? (slide 43)

A
  • mutation frequency to drug resistance among mycobacteria is relatively high
  • must treat with multiple drugs simultaneously and for extended periods (6-9 months) to limit the multiplication of drug resistant mutants, depends on clinical picture, treatment is complex
  • different treatment regimens exist for infections with drug susceptible, multi drug resistant (MDR TB) or extensively drug resistant (XDR TB) strains
31
Q

Prevention of TB?

A
  • better housing and nutrition
  • prompt identification, prophylactic and therapeutic intervention and careful case monitoring (latent disease- especially patients that converted to PPD+)
  • Vaccination:
  • BCG (live, attenuated M. Bovis) vaccine used in areas of high incidence, where disease is endemic
  • variable effectiveness, significantly reduces incidence when administered when people are young (not effective in adults)
  • effective in preventing appearance of disease but not infection with Mtb
  • cannot be used in immunocompromised patients- it is a live organism
  • In US, BCG vaccine is used for young children in close contact with individuals with active disease and military
32
Q

TB xray?

A

pic

IP (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions