tuberculosis Flashcards
What is tuberculosis?
A chronic communicable disease which have lungs as the main target- although other organs can be infected
This condition is caused by mycobacterium tuberculosis which does not produce toxins, rather the tissue damage is typically due to the immune response to the infection where the inflammatory process results in the formation of a granuloma
What are the features of mycobacterium tuberculosis?
It is an aerobic bacteria which undergoes intracellular replication in macrophages and grows very slowly largely due to the time and energy required to synthesize its complex cell wall
What are the features of the cell wall of mycobacterium tuberculosis?
its complex cell wall is made up of mycolic acids (long carbon wax chain) these function to prevent dessication of the cell and protects the cells from lysis after phagocytosis
The cell wall also contains cord factor (trehalose dimycolate) which is a cell wall component that allows strands or cords of daughter cells to remain attached to each other in parallel arrangements this inhibits the migration of neutrophils and is toxic to mammalian cells
How does tuberculosis infection occur?
M. TB can infect any organ but typically infection is through the respiratory tract via inhalation of respiratory droplets where the minimum infectious dose is 10 cells
Adhesive pili of the mycobacteria than attach it to the extracellular laminin protein on the pneumocyte cell surface in the alveoli where they will either invade the pneumocyte replicate themselves and kill the cell or be phagocytosed by an alveolar macrophage which it will survive and replicate
How do mycobacteria survive phagocytosis by alveolar macrophages?
The mycolic acid wall of Tb blocks fusion of the phagosome with the lysosome
What occurs to macrophages that have ingested mycobacteria?
Some macrophages will present mycobacteria antigens to T cells causing them to proliferate and release IFN-gamma which activates macrophages to increase their ability to kill mycobacteria and recruit further macrophages however the lytic enzymes released by the macrophages can cause significant tissue necrosis
Some of the macrophages will transform into epitheloid cells or giant (langerhans) cells
This phase of the disease process can be asymptomatic or induce mild fever
What occurs when macrophages transform into epitheloid cells?
These cells have long stringy nuclei and are ineffective at phagocytosis, they also have a secretory function which allows them to be a mediator of chronic inflammation
There is increased expression of 1alpha-hydroxylase which cinverts 25-OH-cholecalciferol to 1,24-OH cholecalciferol which is a compound which further activates macrophages and leads to a Th2 response and drives fibrosis
What are giant cells?
These occur when come macrophages fuse to from multinucleated giant cells at may be a result of the cells trying to phagocytose the same bacterium
The nuclei in these cells are peripheral and the cells transform into a secretory role which is archetypal for TB granulomas
What are the features of a TB granuloma?
These are an accumulation of infected macrophages including transformed macrophages along with a collar of lymphocytes and fibroblasts
Necrosis will begin to occur in the centre after about 10 days
What type of necrosis occurs in TB granulomas?
Caseous necrosis and coagualtive necrosis which causes a build up of firm and waxy material (from the mycolic cell walls of the bacteria) in the centre of the granuloma
There is also an obliteration of all cellular features seen by the homogenous pink stain when H and E is used
What may occur in an individuals first exposure or infection of mycobacteria?
Some of the infected macrophages will enter the lymphatic system and infect the draining lymph nodes including the hilar and mediatinal nodes
What is a ghon focus?
When there is a small primary granuloma in the lung plus infection of the hilar lymph nodes
What are the outcomes of primary infections with mycobacterium?
Most primary infections will heal (90%) with complete replacement of the caseation necrosis with fibrosis and calcification or there may be a local walling of the necrotic area by collagen with deposition of Ca in the necrotic region with infectious organisms remaining dormant in this loci where they may potentially be reactivated
What factors can influence the outcome of a primary mycobacteria infection?
This is dependent on differences in the dose of infectious agent, genetic variation in immune status and acquired changes in immune status (such as the immature immune system in children, the declining immune system in old age, malnutrition)
What are the possible outcomes of granuloma?
Some lesions will remain small and heal readily allowing total eradication of the infection
Some will cause extensive local damage but contain the infection
Some will release M tb to disseminate throughout the body leading to active infection
