Term
True or False.
Latent TB is contagious in close contact with droplets. |
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Definition
False!
Active and Re-activated is contagious! |
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Term
| What factors contribute to TB susceptibility |
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Definition
1) Malnutrition
2) Poor living conditions
3) Immune compromise
4) Genetic |
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Term
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Definition
1) Cough, Fever, Difficulty Breathing
2) PPD test Acid-fast (lipids retain red dye)
3) X-Ray
4) Culture (3-8 weeks!)
5) IFN-y immune assay to distinguish from non-TB mycobacteria
6) Acid-fast |
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Term
| How does the waxy cell wall of M. tuberculosis contribute to diagnosis? |
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Definition
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Term
| How does TB persist within host? |
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Definition
Binds complement receptor and enters macrophages via phagocytosis (adhesin/invasin genes)
1) Inhibits phag/lys fusion
2) Catalase prevents oxidative damage
3) Down-regulates MHC-II by binding TLR-2 |
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Term
| What is the course of a typical TB infection? |
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Definition
1) Transmitted through aeroloziation
2) Initial infection in alveoloar macrophages
- cytokine release
- hematogenous spread to other organs
- monocytes and lymphocytes recruited to lungs forming GRANULOMA
3) Primary TB infection (cavity formation, lung necrosis, wasting, ect) or latent TB develops
**Host immune response contributes to pathology!** |
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Term
| What are the different immune responses to TB? |
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Definition
1) Cell-mediated- T dominated with cytokine production (CTLs may kill infected macrophages and spread pathogen)
2) Cytokines-
- INF-y activates macrophages
- TNF-a controls but also causes damage
- IL-12, IL-6 , ect
3) Macrophage activation (KEY TO CONTROL)
- T-cell cytokines activate and lead to RNI and ROS
4) Granuloma (control/containment)
- Necrotic center (or caseous) with resident mycobacteria. |
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Term
| How effective in the BCG vaccine for TB? |
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Definition
Good for children (does not prevent infection, but prevents TB)
** future vaccines with recombinant mycobacteria ** |
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Term
| How do you treat/prevent TB? |
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Definition
0-2 months= Isoniazid, Rifampin, Pyrazinamide, Ethambutol
2-6 months= Isoniazid, Rifampin
If resistant, try Streptomycin (aminoglycoside), FQ, PASand Capreomycin)
Isoniazid- inhibit mycolic acid synthesis in mycobacteria
Rifampin- DdRp at beta subunit
Ethambutol- cell wall biosynthesis
Pyrazinamide- unknown |
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Term
| What are the mechanisms of drugs used as a first-line defense against TB? |
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Definition
Isoniazid- inhibit mycolic acid synthesis in mycobacteria
Rifampin- DdRp at beta subunit
Ethambutol- cell wall biosynthesis
Pyrazinamide- unknown |
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Term
| How can you treat people who are infected with TB, but whose infection is not active? |
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Definition
| Prophylaxis with INH/RIF/PYR/ETH |
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Term
Should you be concerned if a person with M. tuberculosis sneezes on you?
What about M. leprae? |
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Definition
1) YES! If active
2) Probably not, need prolonged exposure |
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Term
| What characteristics define M. leprae Pathogenesis? |
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Definition
1) Cell wall has lipoproteins, mycolic acids, lipid-dense "capsule" with PGL-1
2) Slow growing and infects macrophages and Schwann cells (tropism for peripheral nerves)
3) No cultivation or animal model |
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Term
A patients blood tests positive for M. leprae and shows a high bacterial load, with few T cells and foamy macrophages.
What clinical symptoms mighty you predict? |
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Definition
High load (MORE INFECTIOUS)/few T cells/Foamy phages= Lepromatous
Look for Skin nodules, Plaques, Thickened dermis, Nasal mucosa and Peripheral nerve impairment (Schwann cells) |
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Term
A patients blood tests positive for M. leprae and shows a low bacterial load, with many T cells and granulomas
What clinical symptoms mighty you predict? |
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Definition
low load/Many T cells/Granulomas= Tuberculoid
Few flat lesions, Hypopigmentation, Anesthetic in extremities, Sensory nerve Impairment from Inflammation |
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Term
| What type of immune response dominates Tuberculoid Leprosy vs. Lepromatous Leprosy? |
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Definition
1) Tuberculoid (low load/ Many T cells/ Granulomas) involves
Th1 response with macrophage activation and strong DTH response (CD4> CD8)
- Chronic inflammation contributes to granuloma formation and nerve damage.
2) Lepromatous (high load/low T cells/foamy macrophages)
- Th2 response with non-protective antibody response (CTL>CD4) and DTH-
- Bacteria grow and invade schwann cells and macrophages near nerves |
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Term
| What geographical factors should be taken into account when diagnosing the type of Leprosy? |
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Definition
GENETIC COMPONENT TO LEPROSY
Tuberculoid is 90% in Africa/India and 50% in SE Asia
Lepromatous is 90% in Mexico |
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Term
A patient with borderline/lepromatous Leprosy presents with painful nodules and nueritis?
What is causing these symptoms? |
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Definition
50% complication is Erythema nodosum leprosum
Immune-complex driven |
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Term
| How do you diagnose/treat Leprosy? |
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Definition
1) Skin biopsy with H and E and "Fite" stain for acid fast
- Can tell between Tuberculoid and Lepromatous early on by # of AFB
2) Rifampin and Dapsone for 1.5-2 years (Nerve damage irreversible) |
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Term
| What other Mycobacteria are seen in clinical disease? |
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Definition
1) Non-tuberculous (NTM) which grow faster in the environment and infect immunocompromised- ALL difficult to treat
-M. avium-intracellulare causes chronic pulmonary disease in AIDS patients.
- M. marinum- marine organsim leading to "Swimmer's granuloma"
- M. ulcerans- causes Buruli ulcer and skin necrosis in Africa and Australia |
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