The specific bacterium responsible for the development of tuberculosis is Mycobacterium tuberculosis. What exactly does this name mean? The term Mycobacterium refers to the genera of this bacterium, a name based on a substance called mycolic acid present in the bacterium’s outer wall35. The species name – tuberculosis – refers to the clumps of white blood cells called tubercles that isolate the bacteria from rest of the body during infection35. The tubercles are visible in x-rays, appearing as dark spots inside the lungs36. Under the microscope, the M. tuberculosis bacteria appear as tiny rods, usually clumped inside the human cell they are invading. They usually test negative for the Gram test, largely because their cell walls are so thick – the strength of this barrier is but one astounding property of M. tuberculosis that we will touch on in this unit35.
Typically, M. tuberculosis is transmitted by aerosol, with an infected individual coughing or sneezing clumps of bacteria into the air35. Those nearby can easily inhale these clumps, introducing the bacteria into a new environment. Once they enter the body, the bacteria are targeted by a class of white blood cells known as macrophages. The job of these cells is to devour invaders like M. tuberculosis and digest them. In most parts of the body, the macrophages do their job, using harmful oxygen molecules to destroy the bacteria before it can cause TB. The lungs, however, can offer a safe harbor for the bacteria. As air enters the lungs through the trachea, it follows increasingly smaller ducts that spread out like the branches of a tree37. At the very end of these branches are tiny sacs called alveoli, which are surrounded by blood vessels where oxygen passes into the bloodstream and carbon dioxide is expelled37. Inside these alveoli are macrophages that have not yet developed the ability to destroy invading bacteria. They are thus called immature, because they have not matured enough to become “microbe-eating machines”. If the M. tuberculosis bacteria travel into the alveoli, these immature macrophages will engulf the invader, but will not be able to digest them.
To survive inside these immature cells, the bacterium has developed a protective cell wall that can only be described as truly extraordinary. Robert Koch noted the peculiar difficulty of staining M. tuberculosis back in 1882 and speculated that they were surrounded by a “special wall” with “unusual properties”30. However it is only with the tools of modern science that the exact nature of this barrier is finally being understood. The cell wall is organized into a four tiered sandwich, with a layer of peptidoglycan “chicken wire” overlaid by sugar and fat molecules30. The entire cell wall is then wrapped in a layer of wax that makes the bacterium nearly impenetrable30. This formidable wall prevents the bacterium from being digested by the immature macrophages, allowing the bacteria to begin multiplying within its host and steadily growing in number30,35.
Breaking Down the (Cell) Walls
As bacteria numbers exponentially increase in the immature macrophages, the macrophage eventually bursts, releasing a swarm of bacteria into the alveoli38. The sudden surge of free bacteria in the lungs sends out a warning signal to macrophages in nearby alveoli, attracting them to the lysis site38. Once there, the immature cells once again engulf the bacteria, which then replicate and destroy the immature cells as before, forming a vicious cycle38. The destruction of the immature macrophages cannot continue forever though, since, as they die, the cells send out a chemical distress signal to the other members of the body’s immune system, alerting them to the invaders38. Eventually, these additional blood cells of the body’s defense system arrive to attack the bacteria, and bring with them a return message: a chemical that causes the immature cells to finally become full-fledged macrophages35. These adult macrophages then form clumps surrounding the invader, attempting to imprison the bacteria in the alveoli and prevent them from spreading to the rest of the body38. Such collections of macrophages surrounding the bacteria are the tubercules from which the disease gets its name.
At this point, the macrophages surrounding the bacteria try to ingest the invaders, while the bacteria continue to divide and attempt to kill the macrophages35. If the scales in this contest tip towards the immune system’s favor, the bacteria will be devoured and destroyed by the macrophages surrounding them in the tubercule35. While the tubercles can wall off the bacteria from the rest of the lung, this defense is a two-edged sword. The macrophages walling off the bacteria secrete chemicals that also kill the lung cells in that area, turning that spot in the alveolus into a cheese-like pus35. As the macrophages continue to cause damage to the lungs, the tubercule grows larger35. The destruction of lung tissue makes it difficult for the infected individual to breath, leading to the characteristic coughing and bloody phlegm that is characteristic of the disease35. On the other hand, the bacterial population may eventually overwhelm the mature macrophages, at which point a patient is said to have the clinical, infectious version of tuberculosis35. It is at this stage – when other immune cells enter the lung and begin fighting the bacteria – that pneumonia occurs. However, it is important to keep in mind that pneumonia is a generalized term for any inflammatory reaction in the lungs, which can be caused by many kinds of bacteria, viruses, and even pieces of particulate matter like inhaled coal particles39.
Between the two extremes is a stage called latency, in which the macrophages and the bacteria are in stalemate40. This latency period accounts for the third of the world’s population being infected with the TB-causing mycobacteria yet not actually having the disease itself. This population of people serve as a large reservoir of mycobacteria in which the disease may develop in the future40.
HIV and TB
If AIDS and TB were not bad enough by themselves, the two diseases have been found to form a lethal combination. Because their immune systems are weakened by infection with HIV, AIDS patients are more likely to develop tuberculosis41. Further, TBhas been shown to make AIDS worse by further decreasing CD4 T cell counts in the blood42. Furthermore, drug-resistant tuberculosis is almost always fatal in AIDS patients, and has been called the “most malignant opportunistic infection yet associated with HIV infection”41,43.
Diagnosis:
The usual symptoms of tuberculosis include fever, sweating, weight loss, coughing, exhaustion and appetite loss – in other words, signs associated with many ailments including the common cold35. To specifically determine if a patient has TB, a physician usually administers a tuberculin skin test by injecting boiled bacteria under a patient’s arm and observing if a welt forms or not35. Swelling results when a group of T and B Cells specifically formed to defend against the mycobacterium migrate to the site of injection, releasing chemicals that cause a typical inflammatory reaction. The very existence of this anti-TB group of lymphocytes indicates that the individual is infected with the mycobacterium, which has previously stimulated development of this specialized immune arsenal35.
While this is a fairly quick test, further confirmation can be achieved by examining the patient’s lungs by X-rays. In contrast to healthy lungs, those with TB may have holes in them (from the destruction of the tubercles described above) or be filled with fluid (a common reaction to an infection)36. Looking at lung-rays can help corroborate evidence from a skin test, but it is important to remember that it does not prove that a patient has TB, since, as noted above, pneumonia can have many causes36. In addition to chest x-rays, it may be helpful for a physician to examine a patient’s sputum, allowing them to effectively peek inside the lung’s cellular environment by testing for the presence of the M. tuberculosis bacteria.
Comprehension Questions:
1. How does M. tuberculosis usually enter the human body?
2. How can some people test positive for the skin prick test but have no symptoms?
3. What are the major symptoms of tuberculosis?
