So you may have heard that there’s an Ebola outbreak in the western part of Africa. Sadly it’s one of the more deadly strains, with more than 3,500 infected and more than 1,800 suspected deaths. Four missionaries from the United States have returned with the infection for treatment. Two have fully recovered and two have only recently been admitted. While so far it seems to be contained to Africa, fear of its spread to other corners of the world is high. As an immunologist, I often wonder what the immune system is doing during such a rampant infection. Read on to gain an understanding of the immune system’s attempt to control the infection and why it oftentimes is unable to do so.
Ebola virus starts out by infecting the very cells that are supposed to destroy viruses and bacteria. These are immune cells that respond quickly to invasions by foreigners, the first line of defense. When all goes well, these cells kill viruses or bacteria before they become a problem and also help to recruit other immune cells that are highly specialized in preventing infections from becoming unchecked.
The body is full of complex systems including the circulatory, nervous, and reproductive systems. Each of these systems depends on lots of different cell types that need to communicate with each other, i.e. the nerve cells that tell the heart cells to beat. Like these other systems, cells in the immune system rely heavily on communication. And like any good relationship this requires both speaking and listening. One of the ways that immune cells talk to each other is through making molecules called cytokines. These cytokines are the words that are spoken, giving information to the cell that is listening which is done when the cytokine binds to a receptor (the ears).
When viruses infect those initial immune cells, one cytokine is made that acts as a warning to neighboring cells. It communicates two important messages to cells in the area. 1. Don’t let this virus hijack you to make more virus. Prepare all of your defenses to combat the virus if you encounter it. 2. If you have already been infected notify us so we can kill you. It seems a little harsh, but better to get rid of a few infected cells than to let the virus kill the person. Ebola prevents these defense mechanisms from happening by making proteins, VP35 and VP24, which block the cytokine or message from being made and prevents other cells in the area from hearing it even if it is made. Ebola in effect makes the cells in our body hostages and helpless in defending against it.
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By foiling the early method of controlling Ebola infection, the virus is able to accumulate to a level that is beyond the control of our defense mechanisms. And unfortunately, while critical virus-fighting cytokines are impaired after infection, other inflammatory cytokines are made in excessive amounts. This starts a vicious cycle where viral load increases leading to more production of inflammatory cytokines. Inflammation has its uses and is critical in keeping us healthy. But left unchecked it can cause serious harm. The inflammatory cytokines made in an attempt to control Ebola fall on deaf ears as the immune cells that would normally respond to them increasingly die off. What they do target however are blood vessels, causing them to dilate and become “leaky” resulting in the hemorrhage associated with Ebola infection and eventual organ failure.
There is hope however. As you may have heard, the two patients who were flown to Emory in Atlanta have recovered from infection possibly due to treatment with a drug called ZMapp, a cocktail of antibodies directed against the virus. This drug likely neutralizes the virus, preventing it from gaining access to cells. ZMapp hasn’t been successful in every patient receiving it, but at this point it is the best option for a cure from this deadly virus. Here’s hoping, the company that makes it (Mapp Biopharmaceutical) will be able to ramp up production, as the supply is currently depleted.
To make a donation to the brave doctors, nurses, and missionaries trying to combat this epidemic, go to the following organizations:
- Doctors Without Borders
- Samaritan’s Purse–Dr. Brantly who recovered at Emory worked with this missionary group
- SIM USA–Missionaries Dr. Rick Sacra and Nancy Writebol worked with this organization