Nav: Home

Flu infection reveals many paths to immune response

September 28, 2015

A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological pathways. The researchers say their findings may offer key insights for designing more effective vaccines in general.

"During infection, viral proteins are present throughout the cell, not just in the limited compartments that have been the focus of attention in classical immunology," said study leader Laurence C. Eisenlohr, Ph.D., a viral immunologist in the Department of Pathology and Laboratory Medicine at The Children's Hospital of Philadelphia (CHOP). "By investigating how active infections interact with mechanisms deep inside immune cells, we can design vaccines with broader protection against invading pathogens."

The study appears online today in Nature Medicine. Before recently arriving at CHOP, Eisenlohr led this research at Thomas Jefferson University.

Conventional textbook approaches, said Eisenlohr, rely on laboratory studies of "nominal" antigens, usually in the form of purified proteins introduced into cell cultures. An antigen-presenting cell (APC) takes up the proteins and delivers them to a compartment inside itself called the endosome, where the proteins are digested ("processed") into peptides. Those peptides, displayed at the cell surface, stimulate CD4+ T cells, which are vitally important in the body's defense against most infectious agents.

Eisenlohr and colleagues showed in their current study that live influenza virus follows a more complicated path. "During active infection, viral proteins are delivered to regions in the antigen-presenting cell well beyond the endosome, and are consequently subjected to diverse types of processing machinery. As a result, peptides are produced in greater amounts and broader variety compared to the conventional model," he said.

The classical model is said to rely on an exogenous process--in which the antigens are introduced into the APC from outside the cell. The current study, Eisenlohr said, revealed the potency of the endogenous process--in which the virus infects the APC and the APC processes, through a variety of mechanisms, viral proteins that are being produced inside the cell. These processing pathways generate more diverse peptides, which in turn elicit a more robust antiviral response from CD4+ T cells.

Eisenlohr said the study results have implications for designing more effective vaccines, against both influenza and other viruses. "Live vaccines are generally more effective than inactivated vaccines," he said. "That supports the concept that natural infection elicits a larger, more comprehensive immune response than a killed virus. Therefore, if safety concerns preclude use of a live vaccine, we may need to modify inert vaccines to better mimic natural infection--accessing a broader variety of peptides and thus generating a more protective immune response."

He added that "more rational vaccine design will need to consider specific details of each pathogen, to better access those peptides, but the extra work will likely be worth it."
-end-
The National Institutes of Health (grants AI036331 and AI101134) supported this study. In addition to his CHOP position, Eisenlohr is on the faculty of the Perelman School of Medicine at the University of Pennsylvania. Eisenlohr's co-authors are from CHOP, Thomas Jefferson University and Janssen Pharmaceuticals.

"Endogenous antigen processing drives the primary CD4+ T cell response to influenza," Nature Medicine, published online Sept. 28, 2015. http://doi.org/10.1038/nm.3958

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program receives the highest amount of National Institutes of Health funding among all U.S. children's hospitals. In addition, its unique family-centered care and public service programs have brought the 535-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

Children's Hospital of Philadelphia

Related Influenza Articles:

Birds become immune to influenza
An influenza infection in birds gives a good protection against other subtypes of the virus, like a natural vaccination, according to a new study.
Researchers shed new light on influenza detection
Notre Dame Researchers have discovered a way to make influenza visible to the naked eye, by engineering dye molecules to target a specific enzyme of the virus.
Maternal vaccination again influenza associated with protection for infants
How long does the protection from a mother's immunization against influenza during pregnancy last for infants after they are born?
Influenza in the tropics shows variable seasonality
Whilst countries in the tropics and subtropics exhibit diverse patterns of seasonal flu activity, they can be grouped into eight geographical zones to optimise vaccine formulation and delivery timing, according to a study published April 27, 2016 in the open-access journal PLOS ONE.
Influenza viruses can hide from the immune system
Influenza is able to mask itself, so that the virus is not initially detected by our immune system.
Using 'big data' to combat influenza
Team of scientists from the Icahn School of Medicine at Mount Sinai and Sanford Burnham Prebys Medical Discovery Institute among those who combined large genomic and proteomic datasets to identify novel host targets to treat flu.
Rapidly assessing the next influenza pandemic
Influenza pandemics are potentially the most serious natural catastrophes that affect the human population.
Early detection of highly pathogenic influenza viruses
Lack of appropriate drugs and vaccines during the influenza A virus pandemic in 2009, the recent Ebola epidemic in West Africa, as well as the ongoing Middle Eastern Respiratory Syndrome-Coronavirus outbreak demonstrates that the world is only insufficiently prepared for global attacks of emerging infectious diseases and that the handling of such threats remains a great challenge.
Study maps travel of H7 influenza genes
In a new bioinformatics analysis of the H7N9 influenza virus that has recently infected humans in China, researchers trace the separate phylogenetic histories of the virus's genes, giving a frightening new picture of viruses where the genes are traveling independently in the environment, across large geographic distances and between species, to form 'a new constellation of genes -- a new disease, based not only on H7, but other strains of influenza.'
Influenza A potentiates pneumococcal co-infection: New details emerge
Influenza infection can enhance the ability of the bacterium Streptococcus pneumoniae to cause ear and throat infections, according to research published ahead of print in the journal Infection and Immunity.

Related Influenza Reading:

The Great Influenza: The Story of the Deadliest Pandemic in History
by John M. Barry (Author)

Influenza: The Hundred Year Hunt to Cure the Deadliest Disease in History
by Dr Jeremy Brown (Author)

Very, Very, Very Dreadful: The Influenza Pandemic of 1918
by Albert Marrin (Author)

Pale Rider: The Spanish Flu of 1918 and How It Changed the World
by Laura Spinney (Author)

Flu: The Story Of The Great Influenza Pandemic of 1918 and the Search for the Virus that Caused It
by Gina Kolata (Author)

Influenza: A Century of Science and Public Health Response
by George Dehner (Author)

The Influenza Pandemic of 1918-1919 (The Bedford Series in History and Culture)
by Susan K. Kent (Author)

America's Forgotten Pandemic: The Influenza of 1918
by Alfred W. Crosby (Author)

The Great Influenza: The Epic Story of the Deadliest Plague in History
by John M. Barry (Author)

The 1918 Flu Pandemic (Disasters in History)
by Katherine Krohn (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Hacking The Law
We have a vision of justice as blind, impartial, and fair — but in reality, the law often fails those who need it most. This hour, TED speakers explore radical ways to change the legal system. Guests include lawyer and social justice advocate Robin Steinberg, animal rights lawyer Steven Wise, political activist Brett Hennig, and lawyer and social entrepreneur Vivek Maru.
Now Playing: Science for the People

#495 Earth Science in Space
Some worlds are made of sand. Some are made of water. Some are even made of salt. In science fiction and fantasy, planet can be made of whatever you want. But what does that mean for how the planets themselves work? When in doubt, throw an asteroid at it. This is a live show recorded at the 2018 Dragon Con in Atlanta Georgia. Featuring Travor Valle, Mika McKinnon, David Moscato, Scott Harris, and moderated by our own Bethany Brookshire. Note: The sound isn't as good as we'd hoped but we love the guests and the conversation and we wanted to...