B3.009 Mycobacterium Species: A Granulomatous Model

Question 1

physical characteristics of mycobacterium

Answer 1

non motile, non endospore forming rods
small, aerobic
cell walls have a high lipid content and contain waxes with mycolic acid

Question 2

staining of mycobacterium

Answer 2

pink in Ziehl-Neelsen (acid fast)
fluorescence in auramine-rhodamine and auramine O
difficult to gram stain

Question 3

mycobacterium growth characteristics

Answer 3

slow
double approx. every 24 hours
capable of intracellular growth (facultative)

Question 4

are mycobacterium susceptible to post-phagocytic lysis?

Answer 4

no, protected

Question 5

how many species of mycobacterium?

Answer 5

approx. 75 known

Question 6

most significant mycobacterium pathogens in the US

Answer 6

m. avium
m. tubuculosis
m. leprae (<100 per year)

Question 7

why is m.leprae so rare?

Answer 7

subhuman temp required for growth
can grow in mouse foot pads and armadillos
armadillos are reservoir

Question 8

why are mycobacterium groups into complexes?

Answer 8

there are a number of closely related specied

Question 9

MAC

Answer 9

mycobacterium avium complex
comprised of:
m. avium
m. intracellulare

Question 10

dicuss MAC serotypes

Answer 10

approx. 30 serotypes

1, 4, and 8 most common in AIDS patients in US

Question 11

what are environmental saphrophytes

Answer 11

survive well in soil, water, food
can be carried by animals
can’t catch person-person
*drinking shower water

Question 12

discuss the occurrence of MAC

Answer 12

most people are constantly exposed

environmental saprophytes

Question 13

TB complex members

Answer 13

m. tuberculosis
m. bovis
m. africanum
m. microti

Question 14

which TB complex pathogens cause TB in humans?

Answer 14

all but m. microtic
spread by human contact
public health concern

Question 15

is there a risk of environmental or animal transmission of TB?

Answer 15

no environmental reservoirs
few animals (cattle, deer)

Question 16

characterize disseminated MAC

Answer 16

bacteremia and intracellular infection of numerous body tissues with MAC organisms

Question 17

symptoms of disseminated MAC

Answer 17

persistent fever
night sweats
weight loss
diarrhea

Question 18

characterize pulmonary MAC

Answer 18

uncommon
predates HIV epidemic
occurs in immunocompromised patients as a progressive chronic pneumonia
underlying lung disease is often present
organisms are not found elsewhere

Question 19

characterize MAC cervical lymphadenitis

Answer 19

pediatric disease
immunocompetent 2-4 year olds
MAC organisms are confined to the infected lymph node and surrounding soft tissues

Question 20

site of initial TB infection

Answer 20

lungs

Question 21

most common TB presentation

Answer 21

pulmonary

85% of all TB in non-HIV patients

Question 22

TB virulence factors

Answer 22

cord factor (trehalose mycolate)
lipoarabinomannan (LAM)
phosphatidylinositol (PIMS)
-agonist for TLR-2 (which interacts w all gram + bacteria)

Question 23

what is cord factor

Answer 23

surface glycolipids present in virulent strains that causes m. tuberculosis to grow in serpentine cords in vitro
inhibits PMN migration
toxic to mammalian cells
can directly induce granuloma formation

Question 24

how does LAM work?

Answer 24

heteropolysaccharide
inhibits macrophage activation by IFN-y
inhibits IL-12 production by dendritic cells
induces macrophages to secrete TNF-a???

Question 25

what does IL-12 do

Answer 25

major cytokine to induce cells to develop into Th1 cells that can induce type 4 hypersensitivity

Question 26

symptoms of pulm TB

Answer 26

fever
chronic cough
night sweats
weight loss
occasional hemoptysis

Question 27

how does hemoptysis originate in TB patients?

Answer 27

cavitating lesions can rupture and injure blood vessels in the lungs

Question 28

what is extrapulmonary TB?

Answer 28

TB meningitis, TB osteomyelitis
more common in HIV infected patients
may also posses pulm TB

Question 29

why is TB more common in HIV patients?

Answer 29

Th1 cells are the first things affected by HIV

fungal, viral, and TB all more common due to this

Question 30

HAART

Answer 30

highly active anti retroviral therapy

significantly reduced incidence of disseminated MAC in HIV+ individuals

Question 31

MAC epidemiology

Answer 31

one of the most common AIDs related opportunistic pathogens

Question 32

TB epidemiology

Answer 32

leading cause of death due to a single infectious organism in the word

Question 33

what is MDR TB?

Answer 33

multi drug resistant TB

resistant to 2 most important drugs: isoniazid, rifampin

Question 34

risk factors for TB

Answer 34

HIV (50 fold increase over HIV - patients)
diabetes
malnutrition
drug abuse
poverty
low education levels

Question 35

pathogenesis of TB

Answer 35

mycobacteria are intracellular pathogens
engulfed by macrophages and proliferate
delayed type hypersensitivity reaction results in a lesion with:
-infected macrophage and cellular debris at center
-activated macrophages and T cells on the periphery
-caseous granuloma appearing as nodules on CXR (Ghon complex)

Question 36

what happens to granulomas in progressive TB?

Answer 36

expand and cavitate

nodular or cavitary lesions in the apical lung fields are highly suggestive of TB

Question 37

what happens in the majority of TB infections?

Answer 37

immune system contains the infection

small lesions calcify

Question 38

what is latent tuberculosis

Answer 38

viable organisms persisting in lesions
give positive delayed type hypersensitivity on TST
have a 10% risk of reactivation

Question 39

how is disseminated TB read on a TAT?

Answer 39

usually negative

immune system hasn’t confined infection so cannot produce a specific response to the skin test

Question 40

discuss features of the TST

Answer 40

tuberculin skin test
Mantoux test
measure the induration on the skin
5-10 mm = HIV patients
10-15 mm = prisoners
>15 mm = all persons with no risk factors

Question 41

pathogenesis of MAC

Answer 41

in disseminated MAC there is scant recruitment of immune cells
macrophages become densely packed with bacilli, but there is little inflammation
dense infection can be found in the intestinal mucosa, lungs, liver, and spleen

Question 42

do Abs play a role in TB?

Answer 42

no

Question 43

do macrophages die once phagocytosing TB?

Answer 43

no

survive despite being inhibited

Question 44

discuss the role of type 4 hypersensitivity in TB

Answer 44

Th1 cells produce IFN-y to activate macrophages
cause DTH (type 4 ) response
a strong DTH response will usually protect the patient from disease

Question 45

go through the process of antigen presentation by MHC class 2 molecules

Answer 45

1. assembled in ER associated with Ii (invariant chain)
2. MHC2s target to phagolysosome, and Ii is degraded by CLIP in the peptide binding groove
3. HLA DM dissociates CLIP allowing a peptide to bind to MHC (HLA-DO inhibits DM and regulates this step)
4. exogenous antigens are degraded by proteases to produce peptides and are presented by MHC2 to CD4+

Question 46

lab techniques to detect MAC or TB

Answer 46

acid fast smear
cultivation of organism (slow)
identification, speciation, rifampin resistance by PCR
CXR and TST for TB
IFN-y releasing assays (IGRAs) blood test interchangeable with TST

Question 47

most useful body fluids for analysis

Answer 47

sputum

blood

Question 48

BCG vaccine

Answer 48

developed against TB from attenuated m. bovis
doesn’t prevent infection, but may prevent disease
may not give positive TST, only lasts 12 years

Question 49

MAC prevention

Answer 49

preventive therapy in those with advanced HIV

Question 50

treatment which reduced the risk of reactivation

Answer 50

isoniazid preventive therapy (IPT)