Micro Made Simple Chapter 14. Mycobacterium

Front 1

Mycobacteria species and features

Back 1

Include 2 species that almost EVERYONE has heard of.

1. Mycobacterium tuberculosis (causes TB)
2. Mycobacterium leprae (causes leprosy)

Thin rods w/ lipid-laden cell walls. high lipid content makes them "acid-fast" on stain. Only mycobacteria and nocardia are acid-fast.

Only one class of lipids that only acid-fast organisms have (mycosides)

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Acid-fast stain

Back 2

1. Sputum smear covered w/ red stain (carbolfuchsin) and heated to aid dye penetration.
2. Acid alcohol (95% Et2O and 3%HCl) poured over smear
3. counter-stain of methylene blue is applied.

Acid fast organisms resist decolorization with acid and don't become blue because they hold onto red carbolfushin stain.

Like a "fast red sports car," acid-fast organism stains red.

Front 3

Mycobacterium TB

Back 3

Causes tuberculosis. 10 million cases/3 mill deaths/yr.


This acid-fast bacillus (rod) is an obligate aerobe-->thus it likes inhabit the lungs where oxygen is most abundant.

Front 4

Who is especially at risk for developing TB in the US

Back 4

elderly, AIDS, and urban poor.

33% of HIV infected patients harbor Mycobacterium tuberculosis.

Front 5

Tuberculosis

Back 5

The mycobacterium TB grows slowly-->6 weeks for visible growth. Colonies lump together due to hydrophobic lipid nature-->clumped colonies on agar and floating blobs on liquid media.

Front 6

Describe the lipid component of acid-fast organisms, and which is involved in virulence

Back 6

Only mycoside is involved in virulence.

1. Mycolic acid is a large fatty acid

2. Mycoside is a mycolic acid bound to a carbohydrate, forming a glycolipid

3. Cord factor is a mycoside formed by the union of 2 mycolic acids with disaccharide (trehalose).

Cord factor may inhibit neutrophil migration and damages mitochondria. When injected into mice, cord factor causes release of TNF)-->rapid weight loss.

Front 7

Mycoside

Back 7

A mycolic acid bound to a carbohydrate, forming a glycolipid

Front 8

Sulfatides

Back 8

Mycosides that resemble cord factor with sulfates attached to the disaccharide. They inhibit phagosome from fusing w/ lysosome that contains bacteriocidal enzymes. This may be significant in the early facultative intracellular life of mycobacterium TB.

Front 9

Wax D

Back 9

Complicated mycoside (mycolic acid+carb) that acts as an adjuvant (enhances antibody formation to an antigen) that may activate protective cellular immune system.

Front 10

Names of mycosides in TB

Back 10

Mike (mycosides) is a surf-dude who loves waxing (wax D) hiw surfboard (Sulfatides) and has the board attached to leg via a cord (CORD) factor. He's got a cough and severe weight loss.

Front 11

TB pathogenesis and cellular pathogenesis

Back 11

Primarily affects the lung, but can cause disease in any other tissue, and the way it spreads depends on host immune response.The organism interacts with the host and the immune system as follows:

1. Facultative intracellular growth: inhalation into non-immune host-->local infiltration of neutrophils/macrophages. Phagocytosed bacteria not destroyed/multiply n' survive in mac's-->bacteria cruise lymphatics and camp in distant sites. Intracellular existence is cut-short by host development of cell-mediated immunity.

2. Cell-mediated immunity: macrophages that succeed in breaking up invaders run to local node, present to Thelper cells--sensitizing the T cells and prompting their multiplication and entry into circulation to find Mycobacterium TB. T cells release lymphokines to attract macrophages and activate macrophages when they arrive, which can then destroy the bacteria. Unfortunately, macrophage attack results in local destruction/necrosis of lung tissue. (the resulting caseous necrosis likes like granular creamy cheese. This forms a granuloma surrounding the bacteria, which sadly remain viable--which are at bay but can remerge.

Front 12

PPD skin test

Back 12

Following acquisition of cell-mediated-immunity against TB acquisition, any additional exposure to organism results in local delayed-type hypersensitivity reaction (type IV hypersensitivity)

In the skin test, antigenic protein particles from killed M. TB (called PPD or purified protein derivative) results in localized skin swelling and redness, which tells you if a person has been infected.

You need this info since infection may be latent and might not present clinically for years, and you can treat to prevent severe lung/organ damage.

PPD is placed intradermally (just below skin). There, macrophages in skin take antigen and deliver to T cells, which move to skin site, release lymphokines and activate macrophages. 1-2 days later, SHAZAM, skin is red, raised, and hard.

Front 13

Immunology of PPD skin test

Back 13

PPD is placed intradermally (just below skin). There, macrophages in skin take antigen and deliver to T cells, which move to skin site, release lymphokines and activate macrophages. 1-2 days later, SHAZAM, skin is red, raised, and hard.

Front 14

Indication for positive PPD test

Back 14

A positive test is defined as an area of induration (hardness) > 10mm after 48 hrs after 48 hours (time for occurence of type IV hypersensitivity rx.)

(+) @ 5 mm induration in patients who are immunocompromised or have AIDS.

Remember a positive test doesn't mean patient has TB, since patients with active, latent, or cured cases all are positive.

Front 15

False positive test

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Foreigners may have had BCG (Bacillus Calmette-Guerin) vax for TB. This vaccine is debatably effective in accomplishing its goal, but it causes a (+) PPD

Front 16

False negative test

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Some patients who've been infected may not react to PPD despite having been infected in the past. These patients are "anergic"

Anergy can be attributable to : steroid use, malnutrition, AIDS, etc.

In this case, a second injunction with either candida or mumps antigen is given in opposite arm.

A negative response to these common critters raises a red-flag that the patient may really be anergic.

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Clinical manifestations of Mycobacterium TB

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1. initial exposure leads to primary TB (subclinical/asymptomatic). This leads to acquisition of cell-mediated immunity/walling off/suppression of bacteria. These are down but not out, so they can still cause secondary disease or "reactivation TB"

Front 18

TB transmission

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Household members/close contacts 30% infection risk. Of infected individuals 5% will develop TB in 1-2 yrs and 5% will develop reactivation later in life. So there is a 10% lifetime risk for those infected with mycobacterium tuberculosis.

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Primary TB

Back 19

1. transmitted via aersolization respiratory secretions from adult with pulmonary TB.
2. Deposition in highest air-flor region of lung (middle/lower zones)--> small area of pneumonitis w/ neutrophils and edema (Whoah... sounds like pneumonia anyone?)

3) now the bacteria hop into macrophages, multiply, spread via lymph and blood to regional nodes, other lung areas, and distant organs.

Front 20

Asymptomatic primary infection

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Cell-mediated immunity kicks in, bacteria become walled off in caseous granulomsa. Granulomas heal with fibrosis, calcification, and scar formation. These can be too small to be seen on x-ray.

Front 21

two possibilities with TB infection

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As cell-mediated immunity develops:
1. The infection can be contained so that the patient won't realize the infection
2. Disease can become symptomatic

Front 22

Symptomatic primary tuberculosis

Back 22

Rare. Occurs more in children, elderly, and immunocompromised (especially HIV infected patients). These patients have weak cell-mediated immune systems.

In these patients, large caseous granulomas develop in lungs/other organs. Material can liquify-->extrude to bronchi-->leave cavitary lesions on CXR.

Front 23

Secondary reactivatoin TB

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After some variable period of dormancy we can see reactivation, and can affect any organ systems seeded in primary infection.

Likely a period of immunocompromisation can prompt this. HIV patients have 10% chance/year of reactivation vs 10%/lifetime in all other persons.

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Organ systems that can be involved in TB:

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1. pulmonary TB: typically in apical areas around clavicles. Typically reactivates in upper lobe (highest oxygen tension-->increased pulmonary circulation) Slow caseation, liquification, and cavitation follows. Low-grade fever, night sweats, weight loss, and productive cough that may have blood in it. Macrophages and host T-cells battle off the buggers here!.

2. Pleural and pericardial infection: secondary to infected fluid collecting in peri-pulmonary or peri-cardial areas.

3. Lymph node infection: most commonly cervical lymph nodes become swollen, mat together and drain. This is "scrofula"

4. Kidney: red and white blood cells in urine w/ absence of bacteria in gram stain or culture (myco takes weeks to culture and are acid-fast)-->sterile pyuria.

5. skeletal- thoracic and lumbar spine, w/ destruction of intervertebral discs then adjacent bodies (Pott's disease)

6. joints--chronic arthritis of 1 joint

7. CNS- TB subacuate meningitis/granuloma formation in brain

8. Miliary TB- Tiny millet-seed-sized tubercles (granulomas) disseminated over body like a shotgun blast-->kidneys, liver, lungs, and other organs are riddled with tubercles. CXR:"millet-seed" pattern throughout lung (seen in elderly and children).

Front 25

Big picture of TB

Back 25

TB is usually a chronic disease; presents with weight loss, low-grade-fever, and symptoms related to organ systems involved. The slow course may be confused with cancer.

TB is a great imitator, and whenever you have an infection of any organ, you need to have TB in your differential.

Front 26

Diagnosis of TB

Back 26

1. PPD skin test (an exposure in the past)

2. Chest X-ray: May yield granuloma, ghon focus (low), ghon complex (peri-hilar), past scarring in upper lobes, or active TB pneumonitis.

3. Sputum acid-fast stain and culture: when acid-fast tsain or culture are (+), this indicates active infection. Treatment is complex-->different card.

Front 27

Atypical mycobacteria

Back 27

Large group, live in water/soil/ southern U.S. Perhaps 50% of southern population have experienced subclinical infection. They produce a milder version of pneumonia or skin granuloma/ulcer.

Mycobacterium avium-intracellulare & mycobacterium leprae

Front 28

Mycobacterium avium-intracellulare

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An atypical organism that is important in AIDS patients. (Mycobacterium avium-intracellulare (MAI) or (MAC) "Mycobacterium avium-complex" usually infects the birdies, but now is major systemic bac infxn of AIDS patients (late AIDS).

50% of AIDS patients examined @ autopsy have MAI. Not cause of death, but harbringer (strikes at ultimately low T-h levels).

MAI --> chronic wastin-->gross-dissemination to liver, spleen, marrow, and intestine.

Intestinal involvement-->chronic watery diarrhea.

Front 29

Mycobacterium leprae

Back 29

Leprosy or Hansen's Disease. Acid-fast rod. Impossible to grow on artificial media (use footpads of mide, armidillos or monkeys to grow).

6 million global infections.

200 newly diagnosed cases/year (immigrants)

Front 30

Infection with mycobacterium leprae

Back 30

Infection occurs when a person is exposed to respiratory secretions or skin lesions of infected individual.

Front 31

M. leprae infxn: severity is determined by

Back 31

dependent on 2 things

1. bacteria grow better in cooler body temperatures closer to skin surface

2. severity of disease is dependent on host's cell mediated immune response to the bacilli (which like mycobacteria live a facultative intracellular existence).

Front 32

Memory tool for Leprosy

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Acid fast m. leprae cools off on ice cube cuz it loves those cool body areas. It damages the skin (sparing warm armpit, groin and perineum). It also damages superficial nerves, eyes, nose and testes. OUCH!

Front 33

Immunology of Mycobacterium leprae

Back 33

cell-mediated immunity limits spread of bacteria causing inflammation and granulomas, particularly in skin and nerves. Cell-mediated immunity actually modulates the severity of the disease:

1. Lepromatous leprosy (LL)- (BAD CELL IMMUNITY) the severest form of leprosy, patients canNOT mount a cell-mediated response to m. leprae. (possible block of T-h response to m.b. antigens). LL involves skin, nerves, eyes, and testes, but acid-fast bacilli are everywhere. Facial deformity and infertility can occur. Anterior segment involvement-->blindness. Glove and stocking sense-loss-->trauma and secondary infection.

2. Tuberculoid leprosy (TL): Cell-mediated defense can be mounted, thus containing the skin damage to one that's not excessive. Mild/more self-limiting. Type IV hypersensitivity in-tact. Features of this disease include localized superficial, unilateral skin/nerve involvement with 1-2 skin lesions. Enlarged nerves tend to be closest to skin (greater auricular, ulnar, posterior tibial and peroneal). Non-infectious

Front 34

skin test for leprosy

Back 34

lepromin test: measures host ability to mount delayed hypersensitivity to M. leprae antigens (lets you know the integrity of patient immune response, and is also similar to PPD testing).