The Boss lab’s paper focuses on patterns of methylation, modifications of DNA that usually help turn genes off. In comparison with resting B cells, plasma cells need to turn on lots of genes, so their DNA methylation level goes down when differentiation occurs (see graph). PC = plasma cells, PB = plasmablasts. DNAme indicates the extent of DNA methylation. Read more
Are you experienced? Your immune system undoubtedly is. Because of vaccinations and infections, we accumulate memory T cells, which embody the ability of the immune system to respond quickly and effectively to bacteria or viruses it has seen before.
Mandy Ford has teamed up with Craig Coopersmith to investigate sepsis, a relatively new field for her, and the collaboration has blossomed in several directions
“This is an issue we’ve been aware of in transplant immunology for a long time,” says Mandy Ford, scientific director of Emory Transplant Center. “Real life humans have more memory T cells than the mice that we usually study.”
In late-stage sepsis patients, dormant viruses that the immune system usually keeps under control, such as Epstein-Barr virus and cytomegalovirus, emerge from hiding. The situation looks a lot like that in kidney transplant patients, who are taking drugs to prevent immune rejection of their new organ, Ford says.
HIV researchers are becoming increasingly bold about using the “cure” word in reference to HIV/AIDS, even though nobody has been cured besides the “Berlin patient,” Timothy Brown, who had a fortuitous combination of hematopoetic stem cell transplant from a genetically HIV-resistant donor. Sometimes researchers use the term “functional cure,” meaning under control without drugs, to be distinct from “sterilizing cure” or “eradication,” meaning the virus is gone from the body. A substantial obstacle is that HIV integrates into the DNA of some white blood cells.
HIV cure research is part of the $35.6 million, five-year grant recently awarded by the National Institutes of Health to Yerkes/Emory Vaccine Center/Emory Center for AIDS Research. Using the “shock and kill” approach during antiviral drug therapy, researchers will force HIV (or its stand-in in non-human primate research, SIV) to come out of hiding from its reservoirs in the body. The team plans to test novel “latency reversing agents” and then combine the best one with immunotherapeutic drugs, such as PD-1 blockers, and therapeutic vaccines.
The NIH also recently announced a cluster of six HIV cure-oriented grants, named for activist Martin Delaney, to teams led from George Washington University, University of California, San Francisco, Fred Hutchinson Cancer Research Center, Wistar Institute, Philadelphia, Beth Israel Deaconess Medical Center and University of North Carolina. Skimming through the other teams’ research plans, it’s interesting to see the varying degrees of emphasis on “shock and kill”/HIV latency, enhancing the immune response, hematopoetic stem cell transplant/adoptive transfer and gene editing weaponry vs HIV itself.
Zika virus can infect and replicate in immune cells from the placenta, without killing them, scientists have discovered. The finding may explain how the virus can pass through the placenta of a pregnant woman, on its way to infect developing brain cells in her fetus.
Infected placental macrophages. Zika antigens visible in red. From Quicke et al (2016).
“Our results substantiate the limited evidence from pathology case reports,” says senior author Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine. “It was known that the virus was getting into the placenta. But little was known about where the virus was replicating and in what cell type.”
Scientists led by Suthar and Emory pediatric infectious disease specialist Rana Chakraborty, MD, found that Zika virus could infect placental macrophages, called Hofbauer cells, in cell culture. The virus could also infect another type of placental cell, called cytotrophoblasts, but only after a couple days delay and not as readily. Other researchers recently reported that syncytiotrophoblasts, a more differentiated type of placental cell than cytotrophoblasts, are resistant to Zika infection.
The cells for the experiments were derived from full-term placentae, obtained from healthy volunteers who delivered by Cesarean section. The level of viral replication varied markedly from donor to donor, which hints that some women’s placentae may be more susceptible to viral infection than others. Read more
Third in a series on malaria immunology from graduate student Taryn McLaughlin. Sorry for the delay last week, caused by technical blog glitches.
It’s easy for me to find reasons to brag when it comes to research here at Emory. However, even an unbiased person should be excited about the malaria vaccine platform being developed by Alberto Moreno at the Emory Vaccine Center.
His vaccine is based on a chimeric protein (a protein that is a combination of bits and pieces of multiple proteins, a la the creature from Greek mythology) that should get your immune system to target multiple stages of the Plasmodium vivax life cycle. Part of it targets the infectious sporozoite, part of it targets the blood stage merozoite, and part of it will even target the transmitted gamete in future versions. This seems like a no brainer. Of course we should be targeting multiple stages! Read more
Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.
Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.
One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.
As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making itâ€™s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle.Read more
Those of us in the US are fortunate to not have to consider malaria in our day-to-day lives. Globally though, malaria is a serious public health threat with nearly 3.2 billion people at risk and close to half a million deaths every year. The scientific community has been developing malaria vaccines for decades. Yet a robust vaccine still remains elusive. Why?
IMP graduate student Taryn McLaughlin
One set of barriers comes from economics:Â malariaâ€™s strongest impact is in developing countries. But there is just as strong a case to be made for scientific obstacles. Frankly, the parasite (technically a bunch of species of microbes that I’ll just lump together under the umbrella term Plasmodium) that causes malaria is just smarter than we are.
I’m only kidding, but it is a fascinating organism. Its complexity makes it difficult to pin down and also interesting to write about. But before we talk about why Plasmodium is such a pain, let’s first discuss what exactly makes an effective vaccine.Read more
To prevent auto-immune attack, our bodies avoid making antibodies against molecules found on our own cells. That leaves gaps in our immune defenses bacteria could exploit. Some of those gaps are filled by galectins, a family of proteins whose anti-bacterial properties were identified by Emory scientists.
In the accompanying video, Sean Stowell, MD, PhD and colleagues explain how galectins can be compared to sheep dogs, which are vigilant in protecting our cells (sheep) against bacteria that may try to disguise themselves (wolves).
The video was produced to showcase the breadth of research being conducted within Emoryâ€™s Antibiotic Resistance Center. Because of their ability to selectively target some kinds of bacteria, galectins could potentially be used as antibiotics to treat infections without wiping out all the bacteria in the body. Read more
Emory rheumatologist Arezou Khosroshahi was the lead author on a differential diagnosisÂ case report in New England Journal of MedicineÂ published in October, which describesÂ an example of IgG4-related disease. This autoimmune conditionâ€™s name was agreed upon only recently, at an international conference she co-directed in 2011.
This review calls IgG4-related disease an â€œorphan disease with many faces.â€Â It sounds like each case has the potential to be an episode of House. As Khosroshahi explains:
â€œMost patients undergo invasive procedures for resection or biopsy of the affected organ to exclude other conditions. Unfortunately, most of those patients get dismissed by the clinicians, given the good news that their disease was not malignancy. Many of them have recurrence of the condition in other organs after a few months or years.â€
Rheumatologist Arezou Khosroshahi, MD
In the case report, a woman was admitted to Massachusetts General Hospital, because of shoulder and abdominal pain and an accumulation of fluid around her lungs. Surgeons removed a softball-sized mass from her right lung. The mass did not appear to be cancerous, but instead seemed to be the result of some kind of fibrous inflammation, and the patientÂ was treated with antibiotics. Read more
LabTV features hundreds of young researchers from universities and institutes around the United States, who tell the public about themselves and their research. The videos include childhood photos and explanations from the scientists about what they do and what motivates them.Â
The two Emory labs are: Malu Tansey’s lab in the Department of Physiology, which studies the intersection of neuroscience and immunology, focusing on neurodegenerative disease, and Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, which is developing regenerative approaches and technologies for heartÂ disease in adults and children. Read more