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Early Activation of Immune Response Could Lead to Better Vaccines

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a new “first response” mechanism that the immune system uses to respond to infection. The findings challenge the current understanding of immunity and could lead to new strategies for boosting effectiveness of all vaccines. The study, conducted in mice, published online today in the journal Immunity.

Grégoire Lauvau, Ph.D.One way the immune system protects the body against microbes like bacteria and viruses is with memory CD8+ T cells, so named because they can “remember” the invading organisms. If someone is later infected by that same microbe, memory CD8+ T cells recognize the invaders and multiply rapidly, forming an army of cytotoxic T cells to hunt down and destroy the microbes and the cells they’ve infected. This highly specific immune response forms the basis for most vaccines—but it can take several weeks for them to prime the immune system to respond to “real” infections.

This new study shows that the immune system has another, faster method for responding to infections that could be exploited to produce faster-acting vaccines.

“Our research has revealed that pathogen-specific memory CD8+ T cells are reactivated even before they recognize the antigen they previously encountered,” said study leader Grégoire Lauvau, Ph.D., associate professor of microbiology and immunology at Einstein. (Antigens are protein fragments of microbes that trigger an immune response.)

Dr. Lauvau and his colleagues found that this fast-acting immune response is orchestrated by a type of white cell called inflammatory monocytes. After the immune system detects an infection, it recruits monocytes to the affected tissues, where they release inflammatory signals called cytokines. Those inflammatory signals not only activate every memory CD8+ T cell that has previously encountered a pathogen but also stimulate the activation of natural killer cells, another type of white blood cell.

The result is a protective immunologic environment capable of defending against microbes of any kind—viruses, bacteria or parasites. Only later do memory CD8+ T cells specific for that microbe’s antigen begin to multiply, enabling the immune system to launch its focused attack on that particular microbe.

“We’re not saying that recognizing the antigen is unimportant in the immune response,” says Dr. Lauvau. “You do need the antigen later on, to cause memory CD8+ T cells to multiply and to get full pathogen-specific protection. But it doesn’t seem to be needed during the days immediately following re-infection, when this early form of immunity is operating.”

“It’s too early to apply these findings clinically,” said Dr. Lauvau. “For example, we still need to identify all of the cells and signaling molecules that are involved, and learn how and when the immune system switches from the first phase of protection to the second phase, where you have the antigen. But the important concept to take from this study is that it may be possible to improve vaccines by making this early, generalized immune response persist for a longer time until the later, targeted immune response kicks in.”

The lead author of the paper, titled “Inflammatory monocytes activate memory CD8+ T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion” is Saïdi M’Homa Soudja, Ph.D., a postdoc in Dr. Lauvau’s lab. Other contributors are Anne Ruiz, M.Sc., and Julien Marie, Ph.D., at INSERM and Université de Lyon, Lyon, France.

The study was largely supported by grants from the National Institute of Allergy and Infectious Diseases (AI095835), part of the National Institutes of Health, and Einstein funds.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2011-2012 academic year, Einstein is home to 724 M.D. students, 248 Ph.D. students, 117 students in the combined M.D./Ph.D. program, and 368 postdoctoral research fellows. The College of Medicine has 2,522 full time faculty members located on the main campus and at its clinical affiliates. In 2011, Einstein received nearly $170 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center –

Einstein’s founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 155 residency programs to more than 2,200 physicians in training. For more information, please visit and follow us on Twitter @EinsteinMed.

Kim Newman | Newswise Science News
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