TB-> Mycobacteria!!! Microm442 Deck 18 Flashcards
the sole genus of the family mycobacteriaceae (red snappers)
mycobacterium
Includes many environmental organisms
Often found in water, soil, foodstuffs
Nontuberculous mycobacteria
- Pulmonary disease similar to TB
- Lymphadenitis
- Skin and soft tissue diseases
- Disseminated diseases
important determinant of disease presence
and severity for all of these.
Host susceptibility
Acid fastness
Neither gram-negative nor –positive, but staining is often weakly positive.
* Results from the unique cell wall structure, with 60% mycolic acids (waxy coats) and lipoarabinomannan
(LAM in your book, or arabinogalactan below)
* Resists destaining by acid or ethanol
* Renders mycobacterial cells very resistant to drying (likely aids transmission in droplets)
Acid fast staining
(Ziehl-Neelsen or Kinyoun Stain)
- Stain with carbol fuchsin
- Decolorize with acid
alcohol - Counterstain with
methylene blue
Slow-growing and difficult to culture (fastidious) Divided into:
Slow-growing (um, particularly slow-growing?)
* M. tuberculosis, M. leprae are examples
* Generation times often 40x E. coli
* Forms visible colonies >7 day
Fast-growing (um, relatively fast-growing?)
* M. abscessus spp., chelonae are examples
* Forms visible colonies or growth ≤ 7 days
- Carotenoids of various structures
- May be used to speciate clinical isolates (can also use PCR and
biochemical tests)
distinctive pigments
aerobic or not?
aerobic
nonmotile except
m. marinum
host genetics
thought to play important role in
susceptibility/manifestations -> Defects in innate immune receptor signaling, IFN-g pathways
- Difficult to culture in vitro
- Difficult to manipulate genetically
- Renders laboratory
study difficult - Hinders diagnosis
Slow mycobacterial growth make them difficult to treat
- May be less likely to respond to standard antibiotics
- Often grow to high densities before immunity develops
- Can develop resistance to single agents easily
Recent(ish) resurgence
- Poverty
- Crowding
- Malnutrition
- Africa, Asia
hardest-hit - Multidrug
resistance - HIV/AIDS
TB: Impact of HIV
TB disease burden is highest in areas with endemic
HIV
* HIV increases susceptibility to TB infection
* HIV thought to worsen TB outcomes by impacting T-
cell-mediated immunity
* AIDS also increases susceptibility to nontuberculous
mycobacteria (NTM), especially M. avium complex
TB: Clinical features
* Primary: Period soon after initial infection
- Often clinically quiescent
- In the immunocompromised, disseminated disease can occur and be
dramatic - In normal hosts, usually leads to latency (control)
TB: Clinical features
Secondary: Reactivation disease
- Night sweats, fever, weight loss (immune response)
- Cough
- Can infect spinal column (vertebrae) and meninges (central nervous
system) - Much of clinical impact can be attributed to host response
- But host response is necessary for control of infection, so…
TB: Transmission
- Nearly always thought to be from inhaling infectious particles
(droplet nuclei) - Produced by infected person via cough, talking, sneezing
- Can remain suspended in the air for hours
- Small, airborne droplet nuclei can
penetrate to lung airspaces (alveoli),
where infection likely happens - Usually require prolonged, recurrent
exposure for infection
- Bacteria ingested by macrophages
- M. tb can replicate in macrophages, destroying them
- Blood-borne inflammatory cells migrate to infection, ingest bacilli and
continue the process (granuloma) - Effective cellular immunity can take weeks to
develop - Enables rampant early replication
- Infected macrophages can disseminate via
lymphatics to lymph nodes and beyond - Immune response usually contains the infection
parthenogenesis after primary infection
Primary infection, continued:
Immunocompetent hosts:
* Once hypersensitivity/cellular immunity develop, infection usually controlled
* Skin/blood test positivity develop concurrently
* Infection is latently persistent in most
* Usually can’t be reinfected after this stage
* Reactivation can occur later
* Immunocompromised hosts:
* Can get progressive, often disseminated disease
* Manifestations of primary infection varies with age:
* Often progressive in infants, elderly
* More variable in-between (see readings)
Secondary tuberculosis: Reactivation
- Most often occurs within 2 years
- Usually in the apices (tops) of the lungs
- Not clear why- maybe diminished lymphatic drainage
- HIV is a common reason
- Can be due to immunosuppression, subtle or overt
- Necrosis of granulomas, cavitation
- VERY infectious at this point
most people dont develop past latency or so because
most exposed people are treated
- Cellular immunity is critical
- No clear role for humoral (antibody) immunity
- Little to no immune response in early infection
Macrophages have multiple MTb receptors
- Complement receptors (all mycobacteria)
- MTb can resist acid phagolysosome
