Fever; good for more than just a day home from school


“Mom, I think I have a fever,” was the sure fire way to stay home from school as a young child.  One such instance, my mom put her hand to my forehead and told me to go get ready for school. I walked away wondering how she could possibly know I didn’t have a fever without using a thermometer. I decided it could only be one thing: special mom powers.

Parents and doctors have used fevers to monitor infection for decades; no special mom powers after all. Before the discovery of antibiotics, doctors used high fevers to treat various diseases and medical conditions. Even today, increasing body temperature is a used to treat cancer, in combination with other treatment options. Despite fevers being used to treat infection and cancer for decades, it was only recently that doctors and scientists begun to understand how fever treatment works. A recent study by Lin and colleagues suggests fever may help immune cells, called T cells, find their way to the infected part of the body.

T cells help fight off many different types of infections caused by bacteria, viruses, and fungi, collectively referred to as microbes. T cells are part of the adaptive immune system, meaning each T cell is trained to fight one specific invader. Therefore, during infection, the correct T cell (i.e. the one trained to fight that particular infection) needs to receive the message that there is an invader and then travel to the location of invader in the body.

Adhesin molecules on blood vessels act as a Velcro hook, while integrins on T cells act as the Velcro loop.

Adapted from a photo by Hadley Paul Garland

When you get an infection, your body quickly recognizes there is a foreign invader; a microbe that has lost its way and entered enemy territory (your body). Once an invader is identified, your cells begin making molecules to activate the body’s innate immune system to help fight the foreign invader. Some of these molecules can act like messages that travel all over the body to alert other cells of danger or travel to the brain to cause fever. Another subset of these molecules act as bread crumbs to lead immune cells to the infection battlefield or place where the invader was identified. The first to arrive on the battlefield are innate immune cells. Innate immune cells, in combination with other parts of the innate immune response such as fever, and mucus, use their broad arsenal to try to quickly disarm the foreign invader. However, the meanest of microbes can endure the hottest of fevers, escape the stickiest of mucus, and hinder the most brutal attacks by innate immune cells. In the event the innate immune system cannot fight off the invader, messengers are sent to find the right T cell for the fight. Once the T cell trained to fight the infection is called upon, the T cell travels through the bloodstream, the highway for immune cells during infection, following chemokine breadcrumbs to the infection battlefield.

While traveling on the bloodstream highway, T cells put proteins called integrins on their surface – think of them as the loop part of Velcro (Image 2). Cells that make up the wall of the blood vessel near the battlefield put proteins called adhesion molecules on their surface – these act as the hook part of Velcro. When the T cell is traveling past the battlefield, adhesion molecules on the blood vessel wall will bind the integrins and catch the T cells, like a Velcro tether. This ensures the T cells do not miss the battlefield location (Image 3).

T cells traveling through the bloodstream are caught near the site of the infection by binding of T cell integrins to blood vessel adhesin molecules. Clustering of integrins strengthens the bond between the T cell and the blood vessel to ensure the T cell does not pass the infection location on its journey.

Interestingly, fevers can help with this tethering process to get T cells to the right place at the right time. Fevers increase the number of adhesion molecules lining the blood vessel wall at the location of the infection. This increases the chance T cells will be “caught” as they travel through the bloodstream. The study by Lin and colleagues shows fevers increase the activity of integrins, making them extra sticky. T cells sense the increased body temperature during fever and begin making more heat shock proteins, which are proteins that help protect cells from fevers. It turns out heat shock proteins also bring integrins together as clusters and clusters of integrins are stickier than a single integrin. Going back to our Velcro analogy, imagine the hook side of the Velcro trying to grab onto one small piece of the loop. This bond is not going to be very strong. However, if the Velcro hooks attach to multiple small loop pieces, this bond will be much stronger. Further, clustering of integrins on the cell surface acts as an blinking exit sign on the bloodstream highway, signaling to the T cell to leave the bloodstream, by going through the blood vessel wall, to get to the infection battlefield. Once on the other side of the blood vessel, the T cell can begin to fight the microbial intruder.

Fevers are often thought of as a simple consequence of illness without much thought to their actual purpose. However, the studies of Lin and others show inducing fever is an important and intentional process carried out by the body to improve the immune system’s ability to fight infection. We will never know what a human immune system without fever looks like, but one thing is for certain, without warm foreheads there would be a lot more children at home watching cartoons.

Peer edited by Laetitia Meyrueix and Samantha Stadmiller.

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Will dogs save us from allergies?


Picture from: Rennett Stowe

Dog is man’s best friend. Man is dog’s…predictor for allergies?

A recent study showed dogs with owners that suffer from allergies are more likely to suffer from allergies themselves. Researchers also found that dogs that live in urban environments are more likely to have allergies than dogs in rural environments. The same correlation between urban environments and allergies is found in humans. Humans in rural environments come in contact with more species of microbes than their urban counterparts. It is thought that contact with many microbes early in life may protect humans from developing allergies. The same phenomenon is thought to occur in dogs. It appears man and man’s best friend have more in common than originally thought.

Allergies in humans and dogs have been on the rise in the western world. There have been many studies to look at the causes of these allergies in humans, but few have looked into the causes in dogs. Researchers at the University of Helsinki in Finland wanted to change this. We already know that humans who live in urban environments are more likely to have allergies than human who live in rural environments. Hakanen and colleagues wanted to know if the same is true in dogs.

Researchers sent surveys to almost 6000 dog-owners in Finland. The survey asked questions about the dog’s breed, the dog’s current environment (urban v. rural), the dog’s environment at birth, the dog’s allergies, and the owner’s allergies. When analyzing the data, they removed dog breeds known to be genetically prone to allergies, so they could focus on environmental factors. After compiling the data, Hakanen et. al. concluded that dogs who live in urban environments are more likely to have allergies than their rural counterparts. It is important to note, the data are influenced by how much time the dog spends outside and how much contact the dog has with farm animals. Strangely, living in larger human families can also protect dogs from developing allergies. This suggests that we might protect our dogs from allergies; similar to the way they protect us from developing allergies.


Allergy symptoms in dogs can include itchiness, sneezing, hives, constant licking, itchy ears, and itchy, runny eyes. Picture from: Dani

Researchers cannot be certain the cause for differences in allergies between urban dogs and rural dogs and dogs in smaller vs. larger families, but they do have some theories. In humans, the microbiota, or the microbes that live in our bodies and do not cause illness, are an important factor in allergy development. It is thought that humans who grow up in rural areas come in contact with and are colonized with environmental microbes that protect people from allergies. The microbiota is also thought to be important for development of allergies in dogs. Dogs living in rural environments may come into contact with more environmental microbes that protect them from allergies. Furthermore, dogs in larger families likely come into contact with more species of microbes because each family member harbors a unique microbiota.

Though many of the study’s findings are similar between dogs and humans, one difference between human and dog allergies seems to be the impact of birthplace. A dog’s birthplace is not a predictor for allergies in dogs like it is in humans. Researchers think a dog’s birthplace may be less important because dogs are usually removed from their birth environment fairly early (7-8 weeks), when compared to humans (18yrs).

Hakanen and colleagues were able to identify multiple environmental factors important for predicting if a dog will develop allergies. However, the most striking finding of the study was actually in the dog owners. Dogs with owners that have allergies are more likely to have allergies. Though this is not a new finding, it suggests that the factors important to developing allergies in humans and dogs may be the same. The idea that the same factors could influence allergy development in both dogs and humans is particularly intriguing considering dogs suffer mostly skin and food allergies and few respiratory symptoms. Respiratory symptoms from pollen allergies are among the most common in humans. Furthermore, the immune responses that cause allergic symptoms in dogs and humans are different. This suggests the factors influencing allergy development may be important for all mammals despite differences in their immune systems.

There is still more research to be done to determine the factors that lead to allergies in dogs and humans. However, the studies of Hakanen et. al. and others suggest that if we can determine the factors important for developing allergies in dogs, for which it is easier to gather environmental and health information, we may be able to apply these findings to humans. So in addition to being the best listeners, best cuddlers, and our best friends, dogs may just be our best chance to cure our allergies.

Peer edited by Christina Parker

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Why is the Flu such a Big Deal?

With each flu season comes a bombardment of new advertisements reminding people to get a flu vaccine. The vaccine is free to most and widely available, yet almost half of the United States chooses to forgo the vaccine.

When Ebola emerged, there was 24 hour news coverage and widespread panic, but the influenza virus (the flu) feels more familiar and much less fear inducing. This familiarity with the flu makes its threat easy to brush aside. Yet, every flu season is met with stern resolve from the medical community. What’s the big deal with the flu?

What makes the flu such a threat?

Influenza is a globetrotting virus: flu season in the northern hemisphere occurs from October to March and April to September in the southern hemisphere. This seasonality makes the flu a year round battle. The virus also evolves at a blistering pace, making it difficult to handle.

To understand why the flu is able to evolve so rapidly, its structure must be understood.The graphic to the right shows an illustration of the ball-shaped flu virus.


Illustration of flu structure

On the outside of the ball are molecules that let the virus slip into a person’s cells. These molecules are called hemagglutinin and neuraminidase, simply referred to as HA and NA. HA and NA are also used by our body’s immune system to identify and attack the virus, similar to how a license plate identifies a car.

These HA and NA molecules on the surface can chanAntigenic shift in the fluge through two processes. One such process is like changing one license plate number; this is known as antigenic drift. When the flu makes more of itself inside a person’s cells, the instructions for making the HA and NA molecules slightly change over time due to random mutations. When the instructions change, the way the molecules are constructed also changes. This allows the flu to sneak past our immune systems more easily by mixing up its license plate over time.

Another way the virus can evolve is known as antigenic shift. This type of evolution would be more like the virus license plate changing the state it’s from in addition to a majority of its numbers and letters, making the virus completely unidentifiable to our immune systems. Unlike antigenic drift, antigenic shift requires a few improbable factors to coalesce.  

Antigenic shift happens more regularly in the flu when compared to other viruses.For instance, one type of flu virus is able to jump from birds, to pigs, and then to people without the need for substantial change. This ability to jump between different animals enables antigenic shift to occur.


How antigenic shift occur in the flu

This cross species jumping raises the odds of two types of the virus to infect the same animal and then infect the same cell. When both types of the flu virus are in that cell, they mix-and-match parts, as can be seen in the picture to the right. When the new mixed-up flu virus bursts out of the cell, it has completely scrambled it’s HA and NA molecules,generating a new strain of flu.

Antigenic shift is rare, but in the case of the swine flu outbreak in 2009, this mixing-and-matching occured within a pig and gave rise to a new flu virus strain.

This rapid evolution enables many different types of the flu to be circulating at the same time and that they are all constantly changing. This persistent evolution results in the previous year’s flu vaccine losing efficacy against the current viruses in circulation. This is why new flu vaccines are needed yearly. Sometimes the flu changes and becomes particularly tough to prevent as was the case with swine flu. At its peak, the swine flu was classified by the World Health Organization (WHO) as a class 6 pandemic, which refers  to how far it had spread rather than its severity. Swine flu was able to easily infect people, fortunately it was not deadly. The constant concern of what the next flu mutation may hold keeps public health officials vigilant.

Why is there a flu season?

A paper by Eric Lofgren and colleagues from Tufts University grapples with the question “Why does a flu season happen?”. The authors highlight several prevailing theories that are believed to contribute to the ebb and flow of the flu.

One contributing factor to the existence of flu seasons is our reliance on air travel. When flu season in the Australia is coming to an end in September, an infected person can fly to Canada and infect several people there, kickstarting the flu season in Canada. This raises the question: why is flu season tied with winter?

The authors touch on this question. During the winter months, people tend to gather in close proximity allowing the flu access to many potential targets and limiting the distance the virus need to cover before infect another person. This gathering in confined areas likely contributes to the spread of flu during the winter, but another theory proposed in this paper is less obvious and centers around the impact of indoor heating.

Heating and recirculating dry air in homes and workplaces creates an ideal environment for viruses. The air is circulated throughout  a building without removing the virus particles from the air, improving the chances of the virus infecting someone. The flu virus is so miniscule that air filters are unable to effectively remove it from the air. The authors come to the conclusion that the seasonality of the flu is dependent on many factors and no single cause explains the complete picture.

What are people doing to fight the flu?

The flu is a global fight, fortunately the WHO tracks the active versions of the flu across the world. This monitoring system relies on coordination from physicians worldwide. When a patient with the flu visits a health clinic, a medical provider, performs a panel of tests to detect the type and subtype of flu present. This data is then submitted to the WHO flu database, which is publicly accessible.

This worldwide collaboration and data is invaluable to the WHO; it allows for flu tracking and informed decision making when formulating a vaccine. Factor in the rapidly evolving nature of the flu and making an effective vaccine seems like a monumental task. Yet, because of this worldwide collaboration twice a year, the WHO is able to issue changes to the formulation of the vaccine as an effort to best defend people from the flu that year.

Peer edited by Rachel Cherney and Blaide Woodburn.

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H What N What? A Designer Protein Hits the Science Runway

Image ID: 10073 https://phil.cdc.gov/phil/details.asp

TEM Image of Influenza Virion. Content Providers: CDC/ Erskine. L. Palmer, Ph.D.; M. L. Martin, 1981.  Photo Credit: Frederick Murphy

Influenza is a virus that straddles two worlds: that of the past and that of the future. Responsible for more deaths than HIV/AIDS in the past century, the flu is one of the world’s’ most dangerous infectious diseases though it may not seem so, especially in the United States. However, the flu is responsible for millions of cases of severe illness and approximately 250,000 to 500,000 deaths worldwide each year.

Influenza Pandemics
Influenza A and B circulate each flu season, but it is the emergence of new influenza A strains that have been responsible for worldwide epidemics, or pandemics, in the past such as the 1918 ‘Spanish Flu’ pandemic and the 2009 H1N1 pandemic. There are 2 ways a new influenza virus can emerge. Every time the virus replicates, small genetic changes occur that result in non-identical but similar flu viruses: this is called “antigenic drift”. If you get infected with a certain flu virus, or get a vaccine targeting a certain flu virus, your body develops antibodies to that virus. With accumulating changes, these antibodies won’t work against the new changed virus, and the person can be infected again. The other source of change is “antigenic shift”, which results in a virus with a different type of hemagglutinin and/or neuraminidase, such as H3N2 to H1N1. The 2009 H1N1 virus is cited by some as a result of antigenic shift, because the virus was so different than previous H1N1 subtypes; however, as there was no change in the actual hemagglutinin or neuraminidase proteins, it was technically a case of antigenic drift.

Image ID: 13469 https://phil.cdc.gov/Phil/details.asp

This diagram depicts how the human cases of swine-origin H3N2 Influenza virus resulted from the reassortment of two different Influenza viruses. The diagram shows three Influenza viruses placed side by side, with eight color-coded RNA segments inside of each virus. The virus from the 2009 pandemic (right) has HA/NA proteins and RNA from Eurasian and North American swine instead of from humans like in previous years (left two viruses).
Content Provider: CDC/Douglas Jordan, M.A. 2011.


Challenges in Studying the Flu
Scientists and policymakers face many challenges when studying the influenza virus. For instance, the virus can be transmitted among people not showing symptoms and cough, sneeze, or handshake can spread infectious droplets from someone who doesn’t know they’re sick. Scientific study is further complicated by the virus itself: there are 3 antigenic types of influenza virus that infect humans, (A, B, C), with various subtypes and strains. Each year, government agencies work with scientists to decide which strains to target in that year’s vaccine manufacturing. The lag time between production in the spring and the flu season in the winter provides time for unexpected types to emerge.

Image ID: 17345 https://phil.cdc.gov/Phil/details.asp

This is a 3D illustration of a generic Influenza virion’s fine structure. The panel on the right identifies the virion’s surface protein constituents. Content Provider: CDC/ Douglas Jordan, Dr. Ruben Donis, Dr. James Stevens, Dr. Jerry Tokars, Influenza Division. 2014. Illustrator: Dan Higgins.

The H#N# nomenclature for influenza A subtypes refers to the hemagglutinin (H) and neuraminidase (N) proteins that sit on the surface of the virus. There are 18 types of hemagglutinin and 11 types of neuraminidase. Hemagglutinin aids the virus in fusing with host cells and emptying the virus’ contents inside. Neuraminidase is an enzyme embedded in the virus membrane that facilitates newly synthesized viruses to be released from the host cells to spread the infection from one cell to another.

Targeted Therapy
In studying ways to prevent and battle influenza, research scientists have focused their efforts on blocking the actions of neuraminidase and hemagglutinin. Antiviral drugs, such as oseltamivir (Tamiflu®) and zanamivir (Relenza®), bind neuraminidase, both interact with neuraminidase at sites crucial for its activity. The drugs act to render the virus incapable of self-propagating. A computational biologist at the University of Washington in Seattle, David Baker and his team know the hemagglutinin protein well. In 2011, they utilized nature’s design by studying antibodies that bind hemagglutinin in order to design a protein that targets the glycoprotein’s stem in H1 subtype flu viruses and prevent the virion from infecting the host cell. However, antiviral resistance contributed to by antigenic drift, is a serious issue. Researchers much constantly develop new drugs to keep up with changes in the virus.

David Baker and his team now focus their research on the hemagglutinin protein. Utilizing a computational biology approach, they designed a protein that fits snugly into hemagglutinin’s binding sites. They tested their designer protein on 10 mice and found that in mice exposed to the H3N2 influenza virus, their protein worked both as a preventative measure and as a treatment.  Though there is a long road to human testing, this binding protein shows promise for bedside influenza diagnosis as well as a model for possible treatments.

Want to know more? 

Image ID: 8675 https://phil.cdc.gov/phil/details.asp

This photograph depicts a microbiologist in what had been the Influenza Branch at the Centers for Disease Control and Prevention (CDC) while she was conducting an experiment.  Content Provider: CDC/Taronna Maines. 2006. Photo Credit: Greg Knobloch.

Learn how scientists monitor circulating influenza types and create new vaccines each year.

See flu activity and surveillance efforts with the CDC’s FluView and vaccination trends for the United States using the FluVaxView.


Peer edited by Richard Hodge and Tyler Farnsworth.

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Beating Cancer by Releasing the Brakes

Former President Jimmy Carter was diagnosed with stage IV malignant melanoma in 2015, an aggressive form of cancer that spread to his liver and his brain.  Until recently, this would have been a death sentence.  However, after surgery, radiation therapy, and a new type of drug treatment, Jimmy Carter is now cancer-free.

These new treatments do not directly target the cancer cells, but are remarkably saving the lives of stage IV cancer patients. Continue reading

Tom Brady has been Unjustly Denied Tomatoes

Follow Kathryn @kpietro

brady tomoatoAs an avid New York sports fan, I love a good Tom Brady controversy. Many of these controversies are ridiculous and take up too much time during actual news broadcasts (read: deflategate), but other Brady controversies should be taken seriously, including each and every ridiculous haircut he sports. (Remember the Hugh Grant phase?) The latest controversy surrounding Tom Brady combines 2 of my favorite things: ridiculous Tom Brady stories and science.

Let’s talk about the Tom Brady diet. On January 4th the Boston Globe ran a piece on the chef who decides what Tom Brady eats. Chef Allen Campbell chooses a plant-based, organic, GMO-free, sugar-free, caffeine-free, flour-free, pepper-free, mushroom-free, tomato-free, and dairy-free diet for the Brady family. In this article, Campbell makes so many scientifically unsound statements to defend this diet, but one of his statements stood out to me:

“I’m very cautious about tomatoes. They cause inflammation”.

As an immunologist, I feel the overwhelming need to address the frivolous use of the word inflammation. Inflammation is a biological process, which occurs when immune cells migrate to a specific tissue in response to a harmful stimulus, such as an infection or physical injury. This inflammatory response can kill invading pathogens and repair tissue injuries. The inflammatory response elicited by a bacterial infection is the same inflammatory response elicited during a physical injury, like when you are sacked by Justin Tuck in your own end zone on the first play of the Super Bowl.

During an inflammatory response, immune cells are directed to the site of infection or injury by proteins called pro-inflammatory cytokines. Sometimes pro-inflammatory cytokines signal in the absence of a harmful stimulus, which can cause chronic inflammation and autoimmune disease. However, and I cannot stress this enough, tomatoes do not cause chronic inflammation. In fact, the consumption of tomato products has actually been linked to a decrease in chronic inflammation.

Extracts from tomatoes, and even tomato ketchup, decrease pro-inflammatory cytokine production and immune cell migration, which decreases inflammation. Many researchers link the anti-inflammatory effects of tomatoes to a compound called lycopene. In a rodent model, lycopene extracts reduced oxidative compounds that contribute to chronic inflammation associated with gastric ulcers. Furthermore, studies in humans show the addition of tomato juice to people’s diets actually reduces markers of systemic inflammation associated with obesity. The observation that this tomato-based compound decreases inflammation has lead researchers to use derivatives of these compounds to control inflammation through the modification of a key pro-inflammatory pathway, known as the NF-kB pathway. Lycopene derivatives modify essential molecules in this pathway and block the ability of the NF-kB pathway to produce pro-inflammatory cytokines. All of this data supports the exact opposite of what Campbell claims.

While researching for this post I could not find any peer-reviewed, scientific study to back-up the claim that tomatoes cause inflammation. Now, I am by no means suggesting tomatoes will cure all chronic inflammatory diseases, but there is certainly no reason to forego tomato consumption for fear of inflammation. Unfortunately, Brady’s health guru fails to consult scientific facts, and has unnecessarily denied this man/god tomatoes. Dieting can be difficult, and I give Brady credit for sticking to such a stringent diet. I think we can all agree that he deserves a cheat day; I just hope it’s not during the playoffs again.

Peer edited by Deirdre Sackett

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Five foods to get you through cold and flu season

During the winter season, our bodies endure a substantial amount of stress. As temperatures drop, our immune systems can suffer. But staying happy and healthy throughout the cold and flu season is easier than you think. Here are 5 food groups that will help you boost your immune system and fight disease all winter long.

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The 2015 Ig Nobel Prize in Medicine: Kiss me for science!

This year’s Nobel Prizes in Medicine were awarded to William C. Campbell, Satoshi Ōmura, and Youyou Tu whose work to develop novel therapies for the treatment of globally devastating parasitic diseases such as River Blindness, Lymphatic Filariasis (Elephantiasis), and malaria. While this work was certainly important, the greatness of the awardees is already prominently displayed on the front page of the Cell website.

“I also hope that kissing will bring not only love, but also attenuation of allergic reaction.” ~Dr. Hajime Kimata

Less well known are this year’s Ig Nobel prize winners, which were awarded at the 25th First Annual Ig Nobel Prize Ceremony on September 17th, 2015. This year’s Ig Nobel Prize in Medicine was awarded to Hajime Kimata, as well as Jaroslava Durdiaková and colleagues Peter Celec, Natália Kamodyová, Tatiana Sedláčková, Gabriela Repiská, Barbara Sviežená, and Gabriel Minárik. The topic of their research? The health benefits of intense kissing (and other interpersonal activities). Continue reading