Infectious diseases

Ebola

The New Yorker just released a really great, in depth article on Ebola describing how the outbreak began and what scientist are doing to monitor how Ebola is changing as it infects more and more people.  Spoiler alert….scientists do not think this virus will become airborne!  They also cite this recent Science article documenting these changes in Ebola.  Several of the authors have since died from the infection while caring for patients in Africa.

The scientists responsible for monitoring Ebola DNA

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Shoo Flu!

It’s October!  The start of my favorite season: trees turn to fire, crisp cool air makes hiking spectacular, and if you live in St. Louis the Cardinals are fighting to get to the World Series!

I mean that video is some infectious happiness  brought on by a game-winning home run!  But this is a very serious immunology blog so let’s get back to other infectious business. What else does October bring?  The start of flu season!  And therefore time to get the influenza vaccine!

The basis of the influenza vaccine is something called immunological memory…a fancy way of saying that cells of the immune system remember a virus they have seen before and are therefore able to get rid of it more effectively.  Cells of the adaptive immune system (B cells and T cells) are the cells responsible for this memory.  If you have an intruder one time (say into the White House), hopefully you take precautions to prevent it from happening again…like locking the door or keeping security guards nearby to tackle said intruder!  One way our immune system “locks the door” is by creating neutralizing antibodies.  Take a look at the picture of influenza below. The virus is coated in proteins.  Two are very important: hemmaglutinin (HA) and neuraminidase (NA).  HA allows the virus to attach to and gain entry into your cells.  Once inside the cell, influenza hijacks your cells and makes a whole bunch of new virus.  But all of these new viruses need to get out so that they can infect more cells. NA (in green) allow the virus to make its exit.

Influenza Virus–Note the Hemmaglutinin (HA in yellow) and Neuraminidase (NA in green). http://viralzone.expasy.org/all_by_species/6.html

“Not in my house!”

B cells make antibodies that bind to these proteins (especially HA) and therefore block their ability to get into your cells.  Certain types of B cells (memory B cells) are specialized to stick around for a long time after initial infection so that if you are reinfected with the same strain of influenza, lots of these antibodies can be made very quickly.  The influenza vaccines are designed to jump start these B cells.  If you’re infected at a later time during that season, the B cells will be ready to go.  Lots of antibodies will be made preventing the influenza virus from causing you too much sickness.

HA and NA are the basis for the naming system of different influenza strains.  The strains of virus that we are vaccinated with every fall are called H3N2 and H1N1.  These are the strains that cause seasonal influenza.  We’ve all been infected with these viruses, so why isn’t our “immunological memory” able to prevent reinfection? The answer is that influenza is very good at mutating (or changing) itself to avoid our immune response. Especially those HA and NA proteins that are on its surface, the ones we are able to make antibodies against.  In affect, influenza changes so that the antibodies that we make are no longer able to block infection or at least decrease their efficiency at doing so.  Every year, the World Health Organization, collects more than 500,000 samples from patients around the world who have influenza.  They then use these samples to make predictions about what next year’s strain of influenza will look like, particularly regarding HA.  Using this information, WHO is then able to guide production of the next year’s influenza vaccine.

Is it possible to create a vaccine that would be able to last for more than one season and against more strains of influenza?  Of course, scientists are attempting to do this.  If you look at the image above, you can see that HA kind of looks like a tree.  The big leafy parts of the “tree” are what mutates so easily in this virus.  The trunk of the virus stays pretty much the same regardless of strain, making it a good target for vaccines. Another target would be the M2 ion channel shown in the figure.  Like the trunks of HA, M2 doesn’t change too much from strain to strain.  Therefore, vaccines that generate antibodies to these different proteins would be effective against lots of different strains of virus from year to year.

We mostly think of influenza as a nuisance that makes us miss work occasionally.  But during the hysteria over the Ebola outbreak, we should also remember that influenza can be very deadly….50 million people died during the Spanish influenza epidemic in 1918.  More recently, the 2009 H1N1 pandemic caused 200,000 deaths within a year.

Go here for more information on the influenza vaccine.  This post was written with the help of this article.

And one more thing….poll time!  

The confused immune system, asthma, and EV-D68

School’s back in session and with it has come the unavoidable spread of infectious diseases.  Kids don’t always like to share their toys, but they can’t seem to help but bestowing upon their friends their nasty infections!  Gross!  It’s ok…I’m all about exposing kids to lots of germs….good practice for the immune system!  The infection to start out the 2014-2015 school year seems to be one called Enterovirus D68.  As of September 25, 2014, 220 people in 32 states have been confirmed to be infected with the virus.  That’s not such a huge number and it’s definitely not something that we should be flipping out about.

http://mashable.com/2013/06/18/panic-gifs/

Don’t panic!

Most people who are infected have symptoms of a common cold and recover after a few days of coughing, sneezing, and generally feeling blah. But it is causing hospitalizations especially among children who have a history of asthma.  Since there’s not a lot out there about the specific immune response to enterovirus, this week I thought I would discuss one of the reasons why those affected with asthma are oftentimes more prone to suffering complications due to viral infections.

There are a lot of reasons that people develop asthma, but about 50% of those afflicted are considered TH2 high.  Before we get into how this affects infections and asthma, we probably need to understand what TH2 means.  Helper T cells (one type of cell in the adaptive immune system) come in lots of flavors including TH1, TH2, TH17, TH22, TFH, TReg, yada yada yada.  It’s kind of ridiculous, and scientists are constantly adding to that list, probably just to make immunology as confusing as possible.  Or maybe the immune system is just that complicated! We’ll narrow down to TH1 and TH2 though.  TH1 cells “help” (thus the H) other cells to kill viruses and bacteria, usually the sort of nasty bugs that live inside of a cell. Think influenza, HIV, Tuberculosis, enterovirus D68.  TH2 cells on the other hand “help” other cells to kill parasites, worms, and some bacteria that live outside of cells.  (See picture below).  Getting rid of these two different types of pathogens (those that live inside the cell versus those that live outside of the cell) requires different weapons.  Kind of how a police force would use a different approach to a bad guy with hostages inside a house versus a bad guy running around on the streets.Slide1

A TH1 response is required to get rid of viruses, like the enterovirus that is causing so many hospitalizations.  In a lot of people with asthma, the immune system is a little confused and tends to respond to viruses (and other things like allergens) with the wrong “weapons”, using TH2 instead of TH1. One of the weapons that should be used during viral infection is the cytokine Interferon which tells cells go into antiviral mode.  Asthma patients seem to make less of this weapon and instead make use of other weapons that aren’t as useful for getting rid of a virus. (For more information about Interferon and Enterovirus D68 go to the nerd boost!)  Since the wrong (TH2) weapons are being used however, the virus is able to avoid the immune response and to survive much longer.

The use of TH2 also causes them to have asthma exacerbations.  One reason this might be the case is that the virus causes damage to the cells of the lung making it more permeable (or accessible) to allergens and other irritants.  In addition, lots of immune cells are brought to the lung, pummeling the tissue with all sorts of inflammatory stuff that cause the typical features of asthma to show up…wheezing, breathlessness, chest tightness, and coughing. Complications from these asthma flare ups leads to breathing difficulties and might make necessary a trip to the ER.

So to wrap up, Enterovirus D68 isn’t really a bug that the general population needs to be worried about.  But if you have asthma or know of someone who does, it would be wise to keep a close eye on symptoms if you’re feeling sick.  But otherwise, go out into the world, enjoy life, but wash your hands and cover your cough to protect your asthmatic friends!

 

Hijacked by Ebola

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.

If you’re interested in more information go to the Nerd Boost!

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:

I used the following papers to write this article: here, here, here, and here.