Tuberculosis: Mycobacterium tuberculosis

Question 1

Classify MTB

Answer 1

Large, non-motile rod-shaped bacterium

Obligate aerobe

Facultative intracellular parasite (macrophage)

Acid fast (no gram staining characteristics)

Serpentine cord colonies (from cord factor)

Question 2

Name 4 strains of mycobacteria

Answer 2

1) M. bovis (cows)
2) M. avium (birds; seen in AIDS)
3) M. leprae
4) M. tuberculosis

Question 3

What is significant about TB being a facultative intracellular parasite?

(this goes for all other bugs that are similar, i.e. chylamydia)

Answer 3

1) Hard to treat
2) Body uses cell-mediated immunity (Type IV)
3) People exhibit delayed-type hypersensitivity (Type IV)

**when doing an antigen test (PPD skin TB test), people who’ve been exposed will develop a nodule about a day later

Question 4

What’re 3 components of the lipid cell wall of MTB?

Answer 4

1) Mycolic acid
2) Cord factor
3) Wax-D

Question 5

Significance of mycolic acid?

Answer 5

Hydrophobic “shield” to prevent destruction by phagocytosis and complement.

**Also prevents staining and killing from antibiotics

Question 6

Significance of cord factor?

Answer 6

1) Morphology (serpentine cording)
2) Toxic + inhibit neutrophil migration

• *more cord factor = more virulent
• *allows parallel growth of other bacteria

Question 7

Significance of Wax-D?

Answer 7

Major component of Freund’s complete adjuvant

Question 8

How does MTB gain access into macrophage?

Answer 8

Uses mannose receptors (LAM) or Fc receptors

Question 9

What is the secreted protein that can wall off the immune system from MTB?

Answer 9

Antigen 85

Question 10

How does MTB’s slow generation time contribute to it’s virulence?

Answer 10

It can grow “under the radar” of the immune system.

Question 11

What does “TB infection” mean?

Answer 11

It means that MTB is in the body but the immune system is keeping it under control.

Question 12

Are people with TB infection contagious?

Answer 12

NO.

People with TB infection are not infectious. You have to have TB disease to be contagious.

**TB infection = positive PPD skin test

Question 13

What is the #1 predisposing factor for MTB infection?

Answer 13

HIV infection

Question 14

How many stages of TB disease are there?

What is the frequency of people who progress through these stages?

Answer 14

5 stages.

**only 3-4% infected people progress to disease, and very few of those progress to stage 5

Question 15

Which stage is defined by inhaling aerosolized droplet nuclei, followed by ingestion by alveolar macrophage?

How big are the most infective droplet nuclei?

Answer 15

Stage 1.

5 micrometers in diameter

Question 16

Order these by which transmits the most droplet nuclei:

Coughing, talking, singing, sneezing

Answer 16

Sneezing > coughing > singing > talking

**sneezing is the worst since it projects the droplets about 10 feet

Question 17

When does TB infection truly begin?

Answer 17

When droplets reach the alveoli.

**must be sufficiently small to reach it; larger droplets get trapped by airway cilia and do not cause infection

Question 18

Which phase is characterized by MTB replicating in macrophages, bursting them, and then being swallowed by more recruited (but inactivated) macrophages?

Answer 18

Stage 2

**unactivated macrophages cannot destroy MTB

Question 19

Which stage involves T-cell lymphocyte infiltration?

Answer 19

Stage 3

Question 20

What do T-cells release to activate macrophages?

Answer 20

Interferon gamma

**this form cell-mediated immunity to kill MTB

Question 21

Which stage does the infected person become tuberculin positive?

Answer 21

Stage 3

Question 22

What is responsible for the pathological signs/symptoms of TB?

Answer 22

Cell-mediated immunity, which damages the body

Question 23

What are the important cytokines that mediate the immune response to TB?

Answer 23

Interleukin-1 (stimulate fever and immune cells)

TNF (aka cachexin; responsible for the massive weight loss in patients)

Interferon-gamma (activate macrophages + stimulate presentation of infected cells)

Question 24

At which stage does tubercle formation occur?

What is a tubercle?

Answer 24

Stage 3

Localized area of caseation necrosis (they’re big granulomas); has low pH and is anoxic, thereby preventing further MTB replication. However, MTB can hide there for a long time.

Question 25

Which stage involves the growth of tubercles?

How does this happen?

Answer 25

Stage 4

MTB targets unactivated macrophages in the tubercle

Question 26

If a tubercle grows big enough to invade a bronchus, what is the significance of this?

Answer 26

It can spread/disseminate to other parts of the lung or body.

Question 27

What is the hematogenous extrapulmonary spread of TB called?

Answer 27

Miliary tuberculosis

*called this it will look like millet seeds

Question 28

What are the most common sites of TB spread?

Answer 28

1) Genitourinary system
2) Bones (especially lower back)
3) Joints
4) Lymph nodes
5) Peritoneal cavity (i.e. the liver, intestines, etc)

Question 29

What are the two types of lesions formed from miliary tuberculosis? Describe them.

What stage is this?

Answer 29

1) Exudative lesions: accumulated PMN around the tubercle, forming a “soft tubercle.” MTB replicates with no resistance.
2) Granulomatous lesions: body has a hypersensitivity reaction to tuberculoproteins, forming a “hard tubercle”

**This is all stage 4

Question 30

Which stage involves the formation of a Ghon complex?

Describe this.

Answer 30

Stage 5

Tubercles/granulomas will liquefy/cavitate, allowing rapid extracellular replication of MTB, necrosis of the bronchi, and spilling of contents into the airways. These will eventually fibrous, heal, and calcify.

Question 31

On a CXR, what is a Ghon complex? Ghon focus?

Answer 31

Ghon complex = calcified nodules or consolidations in the lung + hilar lymph nodes

Ghon focus = small calcified nodule/consolidation in the lung only (these are also called Simon focus)

Question 32

Where in the lung does primary TB cause damage?

Where does reactivated/secondary TB cause damage?

Answer 32

Primary = upper part of the LOWER LOBES

Reactivated/secondary = lower part of the UPPER LOBES

Question 33

What is multi drug-resistant TB (MDR TB)?

Answer 33

TB that is resistant to isoniazid and rifampicin, the first-line drugs of TB

Question 34

What is extensively drug resistant TB (XDR TB)?

Answer 34

Rare type of TB that is resistant to isoniazid, rifampicin, any fluoroquinolone, and at least one other second line drug (amikacin, kanamycin, capreomycin)

Question 35

Who gets MDR TB or XDR TB?

What method is in place to prevent this?

Answer 35

Patients who do not comply to their treatment regimens and HIV patients

This is the importance of Directly Observe Therapy

Question 36

How do you diagnose TB?

Answer 36

1) Symptoms (esp. night sweats, weight loss, hemoptysis)
2) Signs (cachexia, consolidation, sterile pyruria, etc.)
3) PPD skin test (if positive, then it’s a latent infection, not active disease)
4) CXR
5) Patient history
6) Sputum samples

Question 37

How do you treat TB?

Answer 37

6-9 months of **RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol

• at least two drugs must be used.
• never add a single new drug
• Directly observe therapy
• Monitor toxicity

Question 38

When is a patient no longer infectious?

Answer 38

1) Adequate multi-therapy
2) Respond well the therapy
3) 3 negative cultures

Question 39

What is preventative treatment for TB? Why do this?

Answer 39

1) Take isoniazid 2x/week for 9 months

**keeps those infected from progressing to disease