Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mount Sinai researchers discover new target for vaccine development in abundant immune cells

25.07.2012
Certain white blood cells may be useful in vaccinating against blood-borne infections and HIV

White blood cells called neutrophils, which are the first line of defense against infection, play an unexpected role by boosting antibody production, according to research led by Mount Sinai School of Medicine.

The findings suggest neutrophils have multiple roles within the immune system and function at levels previously unknown to the scientific community. The research, published in Nature Immunology, provides groundbreaking insight into possible new approaches in vaccine development for blood-borne infections and HIV.

Neutrophils are part of the so-called innate immune system—the immune system encoded at birth that remains unchanged—and are at the front lines defending against infection and inflammation. The research was led by Andrea Cerutti, MD, Professor of Medicine at Mount Sinai School of Medicine, and included an international team of investigators that also involved Irene Puga, PhD, of IMIM-Hospital del Mar in Barcelona, Spain, and Montserrat Cols, PhD, of Mount Sinai.

Researchers evaluated healthy human tissues key to the immune system to assess the abundance of neutrophils in the lymph nodes, tonsils, lymphoid tissue in the intestine, and the spleen. They found very few neutrophils in all areas but one—the region of the spleen called the marginal zone. The spleen is an organ whose primary role is as a filtration system for agents that cause infection and inflammation in the body. Looking more closely at these cells, they found that their role spanned beyond the innate immune system.

According to the study, neutrophils in the marginal zone express two molecules called BAFF and APRIL, which then activate immune cells called B-cells in the adaptive immune system, which is more sophisticated and dynamic than the innate immune system. Neutrophils signal BAFF and APRIL to reprogram B-cells to create different classes of antibodies, allowing the immune system to mount a more potent antibody response.

"Our study is important because we discovered a completely new function in an immune cell that has been studied since immunology research began," said Dr. Cerutti. "The interactivity of the neutrophils in the innate immune system with the B-cells of the more sophisticated adaptive immune system shows that neutrophils operate at a much higher level than previously thought and play a very critical role in mounting a robust response to infection."

Dr. Cerutti's team also evaluated the spleens of people with a condition called neutropenia, which is characterized by a shortage in neutrophils and a compromised immune system, and found that the marginal zones in the spleens of these patients had fewer B-cells and antibodies. This demonstrates the necessity of having neutrophils interact with marginal zone B-cells to generate an innate layer of antibody defense. The fact that the research team found an abundance of neutrophils and marginal zone B-cells in the spleens from healthy individuals, but not neutropenic patients, indicates that these cells are primed and prepared to launch multi-level antibody production in healthy humans, even in the absence of a pathogen.

"Since neutrophils boost and reprogram B-cells to strengthen the immune system regardless of whether there is an infection, we may be able to harness them in vaccine development to enhance immune protection," said Dr. Cerutti. "This has significant promise in vaccinating against blood-borne infections, as B-cells are the first line of defense to antigens in the circulatory system. If we can improve vaccines with neutrophil-activating agents, we may have a chance to boost B-cell antibody production, and improve immune protection."

With this new knowledge, Dr. Cerutti and his collaborator Meimei Shan, PhD, from Mount Sinai, are evaluating neutrophil activation and B-cell antibody production in rhesus monkeys vaccinated against Simian Immunodeficiency Virus (SIV), or HIV as it occurs in monkeys, using a vaccine that includes a chemical that activates neutrophils.

"Now that we know that neutrophils are important in the release of powerful antibody-inducing molecules, such as BAFF and APRIL, neutrophils become a potential target for protective vaccines against HIV and other infectious agents," said Dr. Cerutti. "The initial results of this SIV study are encouraging and demonstrate the enormous untapped potential of neutrophils in vaccine development."

Ongoing experiments are testing the generation of antibodies to SIV and the activation of neutrophils and B-cells in the blood, spleen, and intestinal and urogenital tracts, which are major sites of SIV/HIV entry. These measurements are conducted in animals vaccinated in the presence or absence of an agent that stimulates neutrophils. Ultimately, the ability of this vaccine to generate protection against SIV will be tested after challenging the vaccinated animals with a live virus.

This study was funded by the National Institutes of Health in Bethesda, Md.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Of the top 20 hospitals in the United States, Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/.
Find Mount Sinai on:
Facebook: http://www.facebook.com/mountsinainyc
Twitter @mountsinainyc
YouTube: http://www.youtube.com/mountsinainy

Mount Sinai Press Office | EurekAlert!
Further information:
http://www.mssm.edu
http://www.mountsinai.org/

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>