MCRO 320 Lecture 16

tuberculosis

gram pos bacillus, acid fast(mycolic acids=waxy), slow growing, obligate aerobe;
facultative intracellular parasite of macrophages;
extremely conserved genome and low mutation rate w/ long coevolutionary relationship with humans- obligate human pathogens, not in enviro

Southeast Asia, Brazil, Subsaharan Africa; bc HIV most common here; HIV pandemic caused resurgence in TB but decreasing since 2000

atypical! No true endo/exotoxins-- damage is done by host's own immune system.
Intracellular survival in macrophages via iron scavenging, sulfolipids in cell wall prevent phagosome-lysosome fusion=esccape into cytoplasm;
granuloma formation=live inside structure and hide out=prolonged survival;
lipid rich cell wall- waxy mycolic acids=resist phagocytosis and cord factor=glycolipid that causes bacterium to grow in serpentine cords=inhibits leukocyte migration;
lipoarabinomannan(LAM) sim to endotoxin, inhibits macrophage activation and digestion within phagocyte

Neither Gm + or -
Contains mycolic acid (waxy lipid; makes it the most resistant type of bacteria)
impedes entry of chemicals=slow growth, enhances resistance to toxins, glycolipids can stem an inflammatory response

highly transmissible: source case-->aerosolization-->airborne survival-->exposure and inhalation--> depending on susceptibility to infection bacteria enter respiratory tract to infect lung alveoli

1) alveolar macrophages recognize, engulf & attempt to destroy bacilli
2)bac grow on log scale within macrophages, unable to stop bac growth
3)infected areas transform into granuloma(wall of lymphocytes) -->chest pain. Granuloma forms solid caseous center where bac can survive for years, most don't exhibit disease progression (latent state)
4)caseous center liquifies and fills lungs with free-floating bac=pulmonary TB. Bac can go to organs via lymphatic system or bloodstream=extrapulmonary TB

start at lungs--> <10% systematic spread, takes long time.
chest pain, dry cough, structural abnormalities, productive cough, fever, weight loss, weakness, night sweats, poor appetite, cough with increasing mucus, coughing up blood-->extrapulmonary in meninges, lymph nodes, bone and joint sites, genitourinary tract

infection eliminated via innate(no T cell memory) or acquired response;
latent TB capable of active or eliminated infection;
Subclinical (asymptomatic) and active (symptomatic, higher bacterial load, infectious) TB capable of transmission

Resistance via mutations—> resistant bacteria grow within host which can spread resistant bac to others;
Didn't finish antibiotics=resistant bac are selected for and can spread in community

Drug resistant TB=resistant to 1/4 antibiotics ex)INH resistance;
MDR TB= resistant to 2/4 antibiotics;
XDR TB= also resistant to 1+/3 of 2nd line antibiotics, bad side effects, huge concern.

Slight increase in cases