Lecture 8: Acid fast bacteria -Mycobacterium

Question 1

Mycobacterium

• 2 important pathogenic species
• who’s infected?
• shape
• staining
• classification
• growth speed

Answer 1

• 2 important pathogenic sps.
  
  • Mycobacterium tuberculosis, M.leprae
• humans are only species infected
• thin rods w/lipid laden cell walls makes them acid fast on staining
• obligate aerobe
• grows very slowly, taking up to 6 wks for visible growth
• mycosides

Question 2

_________-_ are the class of lipid that only acid fast organisms have.

Answer 2

Mycosides

Question 3

Mycolic acid

Answer 3

a large fatty acid

Question 4

Mycoside

Answer 4

a mycolic acid bound to a carbohydrate, forming a glycolipid

Question 5

Cord factor

Answer 5

• a mycoside formed by the union of 2 mycolic acids with a disaccharide (trehalose)
• found only in virulent strains of M.tuberculosis the - inhibits neutrophil migration and damages mitochondria

Question 6

Sulfatides

Answer 6

• mycosides that resemble cord factor with sulfates attached to the disaccharide
• inhibit the phagosome fusion with lysosome that contains bacteriocidal enzymes

Question 7

Wax D

Answer 7

a complicated mycoside that acts as an adjuvant and may be the part of M.tuberculosis that activates the protective cellular immune system

Question 8

Pathogenesis of Tuberculosis

-Facultative Intracellular Growth

Answer 8

• with the first exposure (usually by inhalation) the host has no specific immunity
• the inhaled bacteria cause a local infiltration of neutrophils and macrophages
• due to various virulence factors the phagocytosed bacteria are not destroyed, they multiply and survive in the macrophages
• the bacteria cruise the lymphatics and blood to inhabit distant sites

Question 9

Pathogenesis of Tuberculosis

-Cell-mediated immunity

Answer 9

• some of the macrophages succeed in phagocytosing and breaking up the invading bacteria
• the macrophages then run toward a lymph node and present bacterial peptides to T-helper cells (CD4+ T cells)
• the CD4+ T cells differentiate into Th1 cells that produce IFN-gamma and TNF-alpha, which together with IFN-gamma and IL-1 produced by macrophages further activating killing mechanisms in macrophages
• the macrophage attack results in local destruction and necrosis of the lung tissue
• the bacteria is kept at bay but remain viable, at some time in the future the bacteria may grow again when the host’s resistance is challenged

Question 10

PPD Skin Test

• what type of hypersensitivity?
• size and timing of postive test
• what does (+)PPD mean?

Answer 10

• following induction of cell-mediated immunity against M.tuberculosis, any additional exposure causes a localized delayed type hypersensitivity (Type IV)
• intradermal injection of antigenic protein particles from killed M.tuberculosis called PPD (Purified Protein Derivative), results in a localized induration that is bigger in diameter than 10mm after 48hrs
• (+)PPD is considered to have latent tuberculosis
• (+)PPD is present in persons with active infection, latent infection, and those who have been cured of their infection

Question 11

PPD Skin Test

-False positive test

Answer 11

• some people from other countries have had the BCG (Bacillus Calmette-Guerin) vaccine for tuberculosis
• *this vaccine is debatably effective in precenting tuberculosis but it may result in positive PPD

Question 12

PPD Skin Test

-False negative test

Answer 12

-some patients do not react to PPD even if they have been infected, these patients are anergic and lack a normal immune response due to steroid use, malnutrition, AIDS, etc.

Question 13

PPD Skin Test

-Alternate Test

Answer 13

-QuantiFERON TB, that measures IFN-gamma produced in response to addition of specific tuberculosis antigens

Question 14

Clinical Manifestations

-Primary Tuberculosis

Answer 14

• M.tuberculosis transmitted via aerosolized droplet from respiratory secretions of an infected individual
• droplets land in areas of lung: middle & lower lung zones & cause a small area of pneumonitis
• bacteria enter macrophages, multiply and spread via lymphatics

Question 15

Clinical Manifestations

-Asymptomatic Primary Infection

Answer 15

• the cell mediated immunity kicks in and contains the bacteria in caseous granulomas
• the organism in these lesions are viable, a calcified tubercle in the middle or lower lung zone is called a Ghon focus

Question 16

PAMP

Answer 16

Pathogen Associated Molecular Pattern

Question 17

See slide 11-12 for explanation of Progression of active Tuberculosis Infection

Answer 17

Don’t forget

Question 18

____% of individuals, M.tuberculosis enters bronchi and is transmitted via coughing -patient infectious

Answer 18

5%

Question 19

____% of individuals, M.tuberculosis spreads to other organs where it remains latent (in ________) under the control of the _______ immune system until __________

Answer 19

95%; adaptive; change in immunocompetency and reactivation

Question 20

Symptomatic Primary Tuberculosis

-occurs in who?

Answer 20

occurs more commonly in children, the elderly, and immunocompromised (HIV infected)

Question 21

Secondary or Reactivation Tuberculosis

-occurs when?

Answer 21

occurence after the bacteria has remained dormant for some time

Question 22

Pulmonary Tuberculosis

• most common site of __________tuberculosis
• infection occurs where?
• process

Answer 22

• most common site of reactivation tuberculosis
• infection occurs in the apical areas of the lung around the clavicles and reactivates in the upper lobe as oxygen tension is highest
• slowly they grow, caseate, liquefy, and cavitate
• slow erosive infection occurs as host macrophages and T cell battle to wall off the bacteria

Question 23

Clinical Manifestations

-Pleural and Pericardial Infection

Answer 23

infection in these spaces results in infected fluid collections around the lung or heart

Question 24

Clinical Manifestations

-Lymph Node Infection

Answer 24

cervical lymph nodes become swollen, mat together, and drain

Question 25

Clinical Manifestations

-Kidney

Answer 25

RBCs and WBCs in the urine, but no bacteria. Known as sterile pyuria

Question 26

Clinical Manifestations

• Skeletal
  
  • > ______’s disease

Answer 26

-involves the thoracic and lumbar spine, destroying intervertebral discs and adjacent vertebral bodies (Pott’s disease)

Question 27

Clinical Manifestations

-Joints

Answer 27

chronic arthritis of at least one joint

Question 28

Clinical Manifestations

-Central Nervous System

Answer 28

subacute meningitis and forms granulomas in brain

Question 29

Clinical Manifestations

-Miliary Tuberculosis

Answer 29

timy millet sized tubercles are spread

Question 30

Diagnosis of TB

Answer 30

PPD skin test
Chest X-ray
Sputum acid fast stain and culture

Question 31

Treatment for TB

Answer 31

• Isoniazide, rifampin, ethambutol, streptomycin and pyrazinamide are the first line of drugs used
• Drug reisitance -MDR-TB & XDR-TB strains require multiple-second line agents for an extended period of time (usu. 18-24 mo)

Question 32

Course of Treatment for TB

-short course treatment

Answer 32

combination of Isoniazide, Rifampin, Ethambutol, and Pyrazinamide for 2 months followed by Isoniazide and Rifampin for further 4 months

Question 33

Mycobacterium Leprae

• causes what
• clinical manifestations depend on
• # of subdivisions of leprosy

Answer 33

• causes leprosy or Hansen’s disease
• clinical manifestions are dependent on:
  a) bacteria grow better in cooler body temps
  b) severity of disease depends on host’s cell-mediated immune response
• 5 clinical subdivisions of leprosy

Question 34

Lepromatous Leprosy (LL)

• _________form of leprosy
• can/cannot mount a cell-mediated immune response?
• primarily where?
• symptoms
• eventually leads to _____ if untreated

Answer 34

• severest form of leprosy, patients cannot mount a cell mediated immune response
• LL primarily involves the skin, nerves, eyes, and testes, but the bacilli are found everywhere
• skin lesions cover the body with all sorts of lumps and thickenings
• nasal cartilage can be destroyed creating a saddlenose deformity
• the anterior segment of the eyes become involved, leading to blindness
• most peripheral nerves are thickened and there is loss of sensation in the extremities
• will eventually lead to death if untreated

Question 35

Tuberculoid Leprosy (TL)

• can/cannot mount a cell-mediated immune response?
• what type of hypersensitivity?
• what test?
• symptoms
• patients are infectious/noninfectious?

Answer 35

• patients with TL can mount a cell-mediated response against bacteria, thus containing the skin damage so that it is not excessive
• delayed hypersensitivity rxn is intact
• lepromin skin test is usually positive
• patients demonstrate localized, superficial, unilateral skin and nerve involvement
• only 1 or 2 skin lesions, well defined, hypopigmented, elevated blotches
• the area within the rash is often hairless with diminished or absent sensation and enlarged nerves near the skin lesions can be palpated
• patients are non-infectious and often spontaneously recover

Question 36

3 other categories of leprosy

Answer 36

represent a continuum between LL and TL and are called [1] borderline lepromatous (BL), [2] borderline (BB) and [3] borderline tuberculoid (BT)

Question 37

Treatment for Leprosy

Answer 37

• several drugs are effective including sulfones such as: dapsone, rifampin, and clofazamine
• prolonged treatment with combination of drugs