B3.009 Mycobacterium Species: A Granulomatous Model Flashcards
physical characteristics of mycobacterium
non motile, non endospore forming rods
small, aerobic
cell walls have a high lipid content and contain waxes with mycolic acid
staining of mycobacterium
pink in Ziehl-Neelsen (acid fast)
fluorescence in auramine-rhodamine and auramine O
difficult to gram stain
mycobacterium growth characteristics
slow
double approx. every 24 hours
capable of intracellular growth (facultative)
are mycobacterium susceptible to post-phagocytic lysis?
no, protected
how many species of mycobacterium?
approx. 75 known
most significant mycobacterium pathogens in the US
m. avium
m. tubuculosis
m. leprae (<100 per year)
why is m.leprae so rare?
subhuman temp required for growth
can grow in mouse foot pads and armadillos
armadillos are reservoir
why are mycobacterium groups into complexes?
there are a number of closely related specied
MAC
mycobacterium avium complex
comprised of:
m. avium
m. intracellulare
dicuss MAC serotypes
approx. 30 serotypes
1, 4, and 8 most common in AIDS patients in US
what are environmental saphrophytes
survive well in soil, water, food
can be carried by animals
can’t catch person-person
*drinking shower water
discuss the occurrence of MAC
most people are constantly exposed
environmental saprophytes
TB complex members
m. tuberculosis
m. bovis
m. africanum
m. microti
which TB complex pathogens cause TB in humans?
all but m. microtic
spread by human contact
public health concern
is there a risk of environmental or animal transmission of TB?
no environmental reservoirs few animals (cattle, deer)
characterize disseminated MAC
bacteremia and intracellular infection of numerous body tissues with MAC organisms
symptoms of disseminated MAC
persistent fever
night sweats
weight loss
diarrhea
characterize pulmonary MAC
uncommon predates HIV epidemic occurs in immunocompromised patients as a progressive chronic pneumonia underlying lung disease is often present organisms are not found elsewhere
characterize MAC cervical lymphadenitis
pediatric disease
immunocompetent 2-4 year olds
MAC organisms are confined to the infected lymph node and surrounding soft tissues
site of initial TB infection
lungs
most common TB presentation
pulmonary
85% of all TB in non-HIV patients
TB virulence factors
cord factor (trehalose mycolate)
lipoarabinomannan (LAM)
phosphatidylinositol (PIMS)
-agonist for TLR-2 (which interacts w all gram + bacteria)
what is cord factor
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
how does LAM work?
heteropolysaccharide
inhibits macrophage activation by IFN-y
inhibits IL-12 production by dendritic cells
induces macrophages to secrete TNF-a???
what does IL-12 do
major cytokine to induce cells to develop into Th1 cells that can induce type 4 hypersensitivity
symptoms of pulm TB
fever chronic cough night sweats weight loss occasional hemoptysis
how does hemoptysis originate in TB patients?
cavitating lesions can rupture and injure blood vessels in the lungs
what is extrapulmonary TB?
TB meningitis, TB osteomyelitis
more common in HIV infected patients
may also posses pulm TB
why is TB more common in HIV patients?
Th1 cells are the first things affected by HIV
fungal, viral, and TB all more common due to this
HAART
highly active anti retroviral therapy
significantly reduced incidence of disseminated MAC in HIV+ individuals
MAC epidemiology
one of the most common AIDs related opportunistic pathogens
TB epidemiology
leading cause of death due to a single infectious organism in the word
what is MDR TB?
multi drug resistant TB
resistant to 2 most important drugs: isoniazid, rifampin
risk factors for TB
HIV (50 fold increase over HIV - patients) diabetes malnutrition drug abuse poverty low education levels
pathogenesis of TB
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)
what happens to granulomas in progressive TB?
expand and cavitate
nodular or cavitary lesions in the apical lung fields are highly suggestive of TB
what happens in the majority of TB infections?
immune system contains the infection
small lesions calcify
what is latent tuberculosis
viable organisms persisting in lesions
give positive delayed type hypersensitivity on TST
have a 10% risk of reactivation
how is disseminated TB read on a TAT?
usually negative
immune system hasn’t confined infection so cannot produce a specific response to the skin test
discuss features of the TST
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
pathogenesis of MAC
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
do Abs play a role in TB?
no
do macrophages die once phagocytosing TB?
no
survive despite being inhibited
discuss the role of type 4 hypersensitivity in TB
Th1 cells produce IFN-y to activate macrophages
cause DTH (type 4 ) response
a strong DTH response will usually protect the patient from disease
go through the process of antigen presentation by MHC class 2 molecules
- assembled in ER associated with Ii (invariant chain)
- MHC2s target to phagolysosome, and Ii is degraded by CLIP in the peptide binding groove
- HLA DM dissociates CLIP allowing a peptide to bind to MHC (HLA-DO inhibits DM and regulates this step)
- exogenous antigens are degraded by proteases to produce peptides and are presented by MHC2 to CD4+
lab techniques to detect MAC or TB
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
most useful body fluids for analysis
sputum
blood
BCG vaccine
developed against TB from attenuated m. bovis
doesn’t prevent infection, but may prevent disease
may not give positive TST, only lasts 12 years
MAC prevention
preventive therapy in those with advanced HIV
treatment which reduced the risk of reactivation
isoniazid preventive therapy (IPT)
