tuberculosis is…
an airborne infection disease caused by Mycobacterium tuberculosis
transmission occurs when an infectious person (with pulmonary TB) - coughs, sneezes, laughs, or sings
prolonged contact is needed for transmission
latent TB or extrapulmonary TB cannot…
transmit the infection
Mycobacterium tuberculosis
aerobic bacillus with a lipid capsule
not visible on gram stain (resists decolourization by acid in one of the steps; hence called ‘acid-fast’ bacilli)
how to detect Mycobacterium tuberculosis
visualised by specific Ziehl-Neelsen stain - they stain pink
better detected by PCR
in a previously unexposed host….
inhaled M. tuberculosis bacteria travel deep into the lungs where they are phagocytosed by alveolar macrophages
once within the macrophages…
the bacteria inhibit formation of phagolysosome (and their microbicidal activity) and proliferate unchecked inside the macrophages
bacterial proliferation within the….
pulmonary alveolar macrophage and air spaces can result in bacterium and can lead to seeding of multiple organs during primary infection
most people are asymptomatic at this stage
what happens after initial/primary infection (3 wks after infection)
the T-cell-mediated response starts
mycobacterial antigens enter draining (hilar) lymph nodes, and are presented by APC to teh T-cells which differentiate into Th1 cells.
Th1 cells produce IFN-g which activates the macrophages and enhances their bactericidal power.
activated macrophages secrete TNF which leads to further monocyte & macrophage recruitment
activated macrophage (now epithelioid cells) and recruiteed monocytes, along with lymphocytes aggregate to form the TB granulomas
Granulomas develop…
central caseous necrosis - a collateral tissue damage as a result of the immune response and cytokine release (inflammation is a double edged sword)
granulomatous inflammation
is caused by an immune reaction to Mycobacterium Tuberculosis
is a specific type of chronic inflammation present in several disease and can even by formed as a reaction to a foreign body
result from persistent activation of a T cell-mediated repsonse by an organism that is difficult to eradicate (mycobacterium tuberculosis)
TB? —> granulomas present too
what forms most of the granulomas
activated macrophages
has indistinct cell boundaries and look like epithelial cells; hence = epithelioid cells
what surrounds epithelioid macrophages in TB granuloma
a “collar’ of activated T lymphocytes
granuloma is surrounded by____ due to chronic inflammation
fribosis -> from attempted healing
cells in granuloma derived by fusion of multiple macrophages
langhans giant cells
what necrosis occurs in the centre of granuloma
caseous necrosis
Ghon focus
are of primary infection in the lung that develops granulomas and caseating necrosis as a result of the Th1 response
located deep in the midzone of the lung
lower part of upper lobe or upper part of lower lobe (right under the pleura)
the hilar lymph nodes involved in the initial infection…
also develop granulomas and caseation
ghon focus + invovled hilar LNs =
ghon complex
possible outcome after primary infection 1. (most people)
most people
- Th1 response halts the infection and leads to killing of the organism and the Ghon conplex heals by fibrosis; often followed by calcification detected on X-ray. in this case, the patient will have acquired immunity against TB
possible outcome after primary infection 2. (sometimes)
the organisms will remain dormant within the initial focus of infection in the lung or extrapulmonary sites; waiting to be reactivated should the host’s immunity drop - this is latent disease or latent TB infection
possible outcome after primary infection 3. (immunocompromised)
the infection progresses and the ongoing immune response results in extensive caseation necrosis and lung tissue damage
- progressive primary TB (active disease)
sometimes hematogenous (blood) spread of the organism (during progressive primary TB) leads to ‘millet seed’ TB granulomas in multiple organs including the lung - miliary TB
healed primary TB on xray
calcified ghon complex
miliary tuberculosis
scaattered granulomas all over lung
bilateral diffuse micronodular radiopaque shadows on chest xray
reactivation or re-exposure (secondary TB)
- vigorous immune reaction
leads to formation of multiple large granulomas with extensive tissue damage. this takes the form of massive areas of central caseous necrosis surrounded by fibrosis (attempted healing from chronic inflammation/infection)
