Biology Behind: The most devious disease you'll find

Greetings everybody

Happy Friday to all of you lovely readers. This week we are focusing on Tuberculosis.

What is Tuberculosis? 

Quick dip into history! Tuberculosis has been following humans closely throughout their history, signs of infection have been found in mummies. 

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Tuberculosis is a communicable respiratory disease (infectious) caused by a bacteria known as Mycobacterium tuberculosis. Tuberculosis manifests itself in many different species, as such not all forms are caused by that one bacteria. M. tuberculosis is the strain commonly associated with disease in humans, however, it's part of a larger group known as the Mycobacterium. tuberculosis complex
This complex includes the following tuberculosis-causing species: 
  • Mycobacterium bovis - clue in the name. This strain mainly affects bovines but can be transmitted to mammalian hosts - like us. 
  • Mycobacterium africanum - main culprit for tuberculosis transmission in West Africa. 
  • Mycobacterium microti - Infects small rodents primarily
  • Mycobacterium pinnipedii - Infects seals
  • Mycobacterium caprae - this species is thought to be able to infect animals including humans. 

All species included in the Mycobacterium tuberculosis complex are classed as obligate pathogens. An obligate pathogen must become active inside the host for it to become infectious and ensure successful transmission from one host to the next. 
Why is tuberculosis such a worrying threat to global health? As we have seen, it is widespread amongst a variety of species. Some of the species involved in the M. tuberculosis complex are able to cross the species barrier separating animal health from human health. 


Size matters:
The individual bacterial agents (M. tuberculosisinvolved in the transmission of this disease are very small in size. An infected individual will sneeze or cough releasing these infectious agents, their size allows for them to remain in the air for a length of time spanning from minutes to hours. Inhalation of just one M. tuberculosis will lead to the host (human or animal) becoming infected with Tuberculosis. Once again the size of this bacteria allows it to migrate from our airways to the terminal structure of our respiratory system - the alveoli. 

Perfect storm for tuberculosis transmission: 
M. tuberculosis has many mechanisms that aid its virulence found inside the bacterial genes. The bacteria that cause tuberculosis are becoming resistant to many of the drugs on the market to treat it. For more on drug resistance and why it matters click here 
Once activated M. tuberculosis triggers many symptoms that can remain mild for many months such as a cough, fever, and weight loss. This allows for the infected individual to infect others, and average 10-15 people can get infected in this way. Tuberculosis has made use of our globalized world to aid its success in transmission. Population expansion, overcrowding and the unregulated movement of people has allowed Tuberculosis to affect all four corners of the world.

Tracking the stages of this disease: 

  1. M. tuberculosis bacteria is engulfed by alveolar macrophages (an immune cell) when the bacteria arrives in the lungs. Once engulfed macrophages produce chemical distress signals (chemokines and cytokines) to recruit other immune cells to the site of infection. 
  2. Inside the macrophage, the bacteria begin replicating exponentially. They block the cell activating bactericidal mechanisms (processes that would lead to the extermination of the bacteria). Eventually, the bacteria cause the premature unprogrammed death of the macrophage known as necrosis
  3. Released bacteria are then taken in by other macrophages responding to the distress signals. The process continues causing growth in necrosis tissue. 
  4. It is 2-4 weeks after the initial infection when T cells (the bodies biggest and badest immune cells) are primed, prepped and ready to target the Mycobacterium 
  5. These cells stop disease progression by halting bacterial replication. A combination of T lymphocytes, macrophages, and other immune cells form a wall around the site of infection (necrosis tissue and infected macrophages) 
  6. The formation of this granuloma leads to the containment of the disease in 90% of infected individuals and halts the progression. 

The threat of Latent TB: 

We know the outcome for 90% of individuals affected by Tuberculosis, what about the remaining 10%? 
M. tuberculosis has one last trick up its sleeve. The bacteria retains the ability to resuscitate itself and become active all over again. 
Whilst most of the bacteria are killed in the granulomas, some manage to block the mechanisms that will lead to their destruction such as: 
  • Preventing the fusion of phagosomes (these are air bubbles like vesicles filled with bacteria inside macrophages) with lysosomes (vesicles containing digestive enzymes that break down bacteria). 
  • Preventing antigen presentation by MHC class 1, Class 2, and CD1 molecules. By preventing this it makes it impossible for our immune system to launch an attack because it doesn't know the target! 
  • Prevents immune cells creating an inhospitable environment. 
Blocking these mechanisms allow the bacteria to enter a dormant/latent state and remain in our alveoli without detection. 
Latent Tuberculosis shows its true insidious nature during this phase.  Bacteria will continue to remain dormant waiting until our bodies immune system becomes weakened by another type of infection (e.g. HIV). Stimulated by the weakened immune system Tuberculosis is activated, allowing for the continued replication as well as disseminating throughout the body.  

Deadly dynamic duo a phrase not saved for superheroes: 
HIV and Tuberculosis are perfect bed buddies. HIV decimates the immune systems of those infected. In its absence,   M. tuberculosis ceases the opportunity and starts its path of destruction all over again
Check out the map below showing the prevalence of individuals infected with both TB and HIV!

Tuberculosis is a threat as a cause of multiple factors; its size, ability to disseminate around the body, route of transmission, growing antibiotic resistance, the threat of latent infections. WHO estimates that a third of the world's population may suffer from latent TB- a ticking time bomb. In the year of 2014 Tuberculosis killed 1.5 million people and was responsible for 1/3 HIV deaths. We have no idea if or when latent Tuberculosis will be activated, there was a case where a man had fallen ill to Tuberculosis that had remained dormant for 30 years (it was gained by his father). 

That was your biology fix for this weekend guys, as always I want to know what you guys thought. Did you find this interesting and if you guys want any diseases looked into any greater detail leave a comment down below!

Over and out! 

NOTIFICATION: I will be changing the name of the blog in the month of December! Please keep up to date with the change in name as I value every one of you as readers. 

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