Smallpox_vaccine

If you’ve been paying attention to the news of late, you’re probably aware of the recent measles outbreak spreading across the country.  Everyone’s talking about it—even the president.  Most children have been vaccinated against measles and other deadly diseases, but those who haven’t are at risk of contracting the disease.  It has been well established that vaccination is the best way to prevent illnesses, and even to eradicate diseases (think polio in the US and smallpox world-wide.)  In fact, President Obama said in a recent speech that the science behind vaccination is “pretty indisputable.”  But what is the science behind vaccines, and why do they work?

In order to understand how vaccines protect us, we have to know some basic information about the immune system, our body’s defense against infection. It’s a complicated system with a wide variety of cell types and functions, and it has some elegant ways of dealing with infection.  When a pathogen, like a bacteria or virus, enters your body, certain cells within your immune system recognize it as foreign.   This is because those cells, called innate immune cells, have receptors embedded within their cell membranes that recognize patterns associated with pathogens.  This means that they aren’t recognizing anything specific—they just know that something foreign has entered your body.

When an innate immune cell senses a pathogen, it engulfs it and chews it up into little pieces known as antigens.  It then displays those antigens on its surface, to signal to other cells that a foreign substance has entered the body.  Some of these innate immune cells send signals to recruit other immune cells to the site of the infection. However, a certain type of innate immune cell, known as the dendritic cell, is able to travel from the site of infection to the lymph nodes.  There, it can interact with another subset of cells in our immune system, the adaptive immune cells.

Even though the innate immune cells can only recognize that something is foreign, the adaptive immune cells can go further—they can recognize specific pathogens and mount a targeted response.  The two types of adaptive immune cells, T cells and B cells, have very specific receptors on their surfaces.  These receptors recognize specific antigens (those pieces of pathogen chewed up and displayed by innate immune cells). Each adaptive immune cell can recognize a specific piece of a specific pathogen—but the design of those receptors is random.

We have thousands of B cells and T cells circulating in our blood, each with a receptor that recognizes a different antigen.  As they move around, they stop by the lymph nodes, where the T cells check to see whether a dendritic cell is displaying an antigen they recognize.  Usually, T cells don’t find anything they recognize and move on.  When we have an infection, however, a few T cells recognize the antigen being presented by a dendritic cell.  Those cells then become activated—their specific receptor is suddenly important!  They then activate B cells which recognize the same antigen.

Because the activated cells are crucial to fight the current infection, they make many, many identical copies of themselves (this is why your lymph nodes swell when you have an infection).  During this process, they modify their receptors to be even better at recognizing their specific antigen.  Before the immune system came into contact with a specific pathogen, there were a few cells in the body that could recognize its antigen; however, during an infection, the immune system makes thousands of cells designed to specifically recognize and deal with that pathogen.  Activated T cells destroy virally infected cells and help other cells of the immune system to perform their function, while B cells make an important substance known as antibody.  Antibodies can recognize antigen without being attached to a cell, which allows them to move through the bloodstream to help defeat the infection.

An important aspect of this protection is a process called immunological memory.  During an infection, many T cells and B cells are produced to fight the pathogen.  After the infection has been cleared, most of those activated cells are no longer needed and undergo cell death.  However, a few of those cells become memory cells.  These cells have a very specific receptor for a pathogen, and can become activated very quickly if they encounter that pathogen again.  This means your immune response will be much quicker the second time you encounter a pathogen.

For example, think of the chicken pox—an infection many of us had when we were younger, before there was a vaccine.  As the virus infected our bodies, the T cells and B cells that were able to recognize it were activated.  They multiplied and modified their receptors to be more specific, but that process took several days. That’s why we got sick—our bodies were fighting the virus, but they needed time to mount their defenses.  After we got over the chicken pox, a few memory T and B cells remained in our system.  Now, if we’re exposed to the chicken pox, those memory cells recognize it right away and multiply, getting rid of the virus before it can make us sick.

What does this have to do with vaccines? When scientists design a vaccine, they are essentially hijacking the power of the immune system in order to protect us. Edward Jenner was the first person to discover that we can use our own immune systems to protect us against specific infections. In 1798, he injected a small boy with cowpox—a virus similar to the much more deadly smallpox. The boy’s adaptive immune system made antibodies and memory cells against the cowpox virus. In a controversial move, Jenner then exposed the boy to smallpox—and he didn’t get sick! Because cowpox and smallpox are very similar in structure, the antibodies made against cowpox were able to bind to the smallpox virus, protecting the boy from getting sick.

Vaccination;_-Dr_Jenner_performing_his_first_vaccination,_17_Wellcome_V0018142

Edward Jenner performs the first vaccination.

Nowadays, most vaccines are made of an inactivated form of a pathogen. By injecting that into our tissues, we elicit an immune response, without the added side effect of actually getting sick. Vaccines also sometimes contain an adjuvant, a substance designed to make our immune reaction more robust. The design of vaccines is carefully tested, and ensures that our body makes plenty of antibodies and memory cells specific for what we’re being vaccinated against. Then, if we do come into contact with the pathogen, the memory cells are quickly activated and clear the virus or bacteria before it can cause an infection. So, getting vaccinated protects us from a specific pathogen, like the measles, without being exposed to anything dangerous.  (Vaccines do have some side effects—but they are rare and mostly mild, and autism is not one of them.)
So what happens to those who are too young or too immuno-compromised to be vaccinated? Consider a scenario where a boy who has received the measles vaccine comes into contact with the virus. His memory cells will be activated and quickly clear the virus, before it is able to establish an infection. Without being able to establish an infection, the virus can’t spread. The measles is airborne—when an infected person coughs or sneezes, the virus is present in the small droplets that are released.  It can stay in the air for several hours, making it incredibly contagious.  But, if the person exposed has been vaccinated, the potential for spread of the virus stops when their immune system kills it off.  So if the exposed boy, who has been vaccinated, then plays with his younger sister, who is too young to be vaccinated, there is no chance he will pass the measles on to her.

In this case, the younger sister is benefiting from her older brother’s immunity.  In the same way, the young and immuno-compromised people in our communities rely upon those of us that are vaccinated to protect them. This is what is known as herd immunity—the vast majority of people, or the “herd,” have received the vaccine and are immune, thereby preventing the spread of pathogens to those who are not.  When most people are vaccinated, the chance of a pathogen jumping from one susceptible person to another is very low. Because diseases like the measles are so contagious, the vast majority of people must be vaccinated in order for herd immunity to function properly.  This is why we’re seeing an outbreak of the measles—even a small increase in the number of unvaccinated people in a community can dramatically affect how well a pathogen can spread.

How do we know that vaccination works?  Take a look at this document from the Centers for Disease Control that breaks down the numbers of US infections of certain diseases before and after we had vaccines for them.  Some of these diseases haven’t even been seen here since the introduction of their vaccine.

The science is clear: vaccines take advantage of our immune system to protect us from infections.  And they work—they prevent a wide array of serious illnesses, and have even eliminated some deadly diseases from our country and our planet altogether. An important thing to remember is that herd immunity is an absolutely essential piece of the vaccination puzzle.  It protects the most medically vulnerable people in our community: newborns and infants, people with faulty immune systems, and transplant and cancer patients on immuno-suppressing drugs.  Because the measles is incredibly contagious, herd immunity is particularly important to prevent its spread—and, as we’re seeing right now, it takes a lot of vaccinated people to protect those who aren’t.

By Jaimee Hoefert

The Centers for Disease Control website houses a huge amount of material on vaccines and vaccine-preventable diseases. You can find both a breakdown of the basics and some more in-depth discussions of vaccines here: http://www.cdc.gov/vaccines/

Want a visual look at how vaccines work? Check out this animation:http://www.historyofvaccines.org/content/how-vaccines-work

If you want to learn more about how vaccine studies are designed, the polio vaccine study is an amazing example.  Find more information about its design here, or read about the history of the vaccine and trials here.

Posted by Science Buffs

A CU Boulder STEM Blog

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