all immunology stories

Initial human trial of Type 1 diabetes treatment begun

404132862 — Thu, 13 Mar 2008 15:11:30 -0400

Scientists at the Massachusetts General Hospital (MGH) have initiated a phase 1 clinical trial to reverse type 1 diabetes. The trial is exploring whether the promising results from the laboratory of Denise Faustman, Associate Professor of Medicine at Harvard Medical School, can be applied in human diabetes.

Blood stem cells fight invaders

404132862 — Thu, 29 Nov 2007 14:21:28 -0500

No other stem cell is more thoroughly understood than the blood, or hematopoietic, stem cell. These occasional and rare cells, scattered sparingly throughout the marrow and capable of replenishing an entire blood system, have been the driving force behind successful bone marrow transplants for decades. Scientists, for the most part, have seen this as the hematopoietic stem cell’s (HSC) singular role: to remain in the bone marrow indefinitely and to replenish blood and immune system cells only when called upon.

Pursuing a cholera vaccine

50443248 — Tue, 15 May 2007 09:47:03 -0400

The reports from Dhaka are hopeful. It is 2005, and Dr. Firdausi Qadri and colleagues at the International Center for Diarrheal Disease Research, Bangladesh, are testing a new cholera vaccine on children. In their study, a single dose of live, crippled bacteria goes down easily in a fizzy drink. Within days, most of the children are showing exactly the kind of robust immune response that should enable them to fend off an attack from the deadly pathogen, with no notable side effects.

The study follows a similar success immunizing adults in the same city. The stage is now set for a large-scale trial to test the vaccine, known as Peru-15, to prevent the seasonal flare-ups of life-threatening diarrhea that dog the poor in Bangladesh and other regions of the developing world.

Saving your self from yourself

Wed, 11 Jul 2007 12:09:08 -0400

"Your gut is a complicated place," notes Shannon Turley, an assistant professor of pathology at Harvard Medical School. In addition to processing food three or more times a day, an intestine needs to protect you from being damaged by yourself.

For the food-processing task, your gut carries a small army of bacteria that turn steak and potatoes into tiny molecules your blood and gut can handle. But it also is continually tested with course after course of potentially dangerous molecules that cause a variety of ailments like inflammatory bowel disease. Turley and her colleagues are trying to find out how the gut manages to destroy these toxic molecules without harming "self," normal tissues and organs, or the good bacteria that feed them.

Key antibody IgG links cells' capture and disposal of germs

Thu, 12 Jul 2007 09:35:21 -0400

Scientists have found a new task managed by the antibody that's the workhorse of the human immune system: Inside cells, immunoglobulin G (IgG) helps bring together the phagosomes that corral invading pathogens and the potent lysosomes that eventually kill off the germs.

The research, by Axel Nohturfft at Harvard University and colleagues at Harvard, Massachusetts General Hospital, and the Massachusetts Institute of Technology (MIT), appears this week in the Proceedings of the National Academy of Sciences (PNAS).

Cells that work themselves to death

Thu, 12 Jul 2007 09:57:33 -0400

When you're fighting flu or any other infection, your body mobilizes battalions of cells to defend against the invading viruses or bacteria. But once the invaders have been defeated and you've recovered from aches, fever, headaches, and a sore throat, your body has to get rid of the now-unneeded fighting cells. If left alone, they can attack healthy tissues.

One way to muster them out is signaling them to commit suicide. Sounds cruel, but it's a natural protective process called "apoptosis." It is the same strategy that the human immune system uses to get rid of tumor cells.

Vitamin D critical to human TB response

70652986 — Mon, 26 Mar 2007 06:25:09 -0400

Vitamin D plays a critical role in the human body's response to tuberculosis, according to new research that explains why people of African descent are more susceptible to TB.

The research also suggests a new way to fight one of the world's deadliest diseases: with a simple dietary supplement.

Tuberculosis, usually caused when a person inhales tuberculosis bacteria, killed an estimated 1.7 million people in 2003 and is the leading cause of death for people afflicted with AIDS, according to the World Health Organization (WHO).

People of African descent are more susceptible to tuberculosis than Caucasians, with higher rates of infection and more severe cases once infected, trends that had puzzled researchers until now. Sub-Saharan Africa, for example, has the world's highest per capita rates of both tuberculosis cases and deaths from the disease, roughly twice the next-highest region, according to WHO statistics.

The research, conducted by a team from the University of California, Los Angeles (UCLA), and the Harvard School of Public Health, shows that vitamin D plays a key role in the production of a molecule called cathelicidin, which kills the tuberculosis bacteria.

The body produces vitamin D when sunlight hits the skin. The skin pigment melanin - more abundant in darker skin - shields the body from the sun's rays, reducing damage from ultraviolet light, but also reducing vitamin D production.

How gold and other medicinal metals function against rheumatoid arthritis and other autoimmune diseases

70652986 — Mon, 26 Mar 2007 06:24:51 -0400

Gold compounds have been used for the treatment of rheumatoid arthritis and other autoimmune diseases for more than 75 years, but until now, how the metals work has been a mystery. Harvard Medical School researchers report in the Feb. 27, 2006 issue of Nature Chemical Biology that special forms of gold, platinum, and other classes of medicinal metals work by stripping bacteria and virus particles from the grasp of a key immune system protein. "We were searching for a new drug to treat autoimmune diseases," says Brian DeDecker, PhD, Harvard Medical School post-doctoral fellow in the Department of Cell Biology and a study co-author. At the time of this work, DeDecker was in the Harvard Medical School Institute of Chemistry and Cell Biology, which uses powerful chemical tools to illuminate complex biological processes and provide new leads for drug development. "But instead we discovered a biochemical mechanism that may help explain how an old drug works."

DeDecker and co-author Stephen De Wall, PhD, undertook a large-scale search for new drugs that would suppress the function of an important component of the immune system, MHC class II proteins, which are associated with autoimmune diseases. MHC class II proteins normally hold pieces of invading bacteria and virus on the surface of specialized antigen presentation cells. Presentation of these pieces alerts other specialized recognition cells of the immune system called lymphocytes, which starts the normal immune response. Usually this response is limited to harmful bacteria and viruses, but sometimes this process goes awry and the immune system turns towards the body itself causing autoimmune diseases such as juvenile diabetes, lupus, and rheumatoid arthritis.

During their search through thousands of compounds they found that the known cancer drug Cisplatin, a drug containing the metal platinum, directly stripped foreign molecules from the MHC class II protein. From there, they found that platinum was just one member of a class of metals, including a special form of gold, that all render MHC class II proteins inactive.

In subsequent experiments in cell culture, gold compounds were shown to render the immune system antigen presenting cells inactive, further strengthening this connection. These findings now give researches a mechanism of gold drug action that can be tested and explored directly in diseased tissues.

Bacterium proves essential to immune system development

70652986 — Mon, 26 Mar 2007 06:21:13 -0400

In the July 15, 2005 Cell, a team led by Dennis Kasper, the William Ellery Channing Professor of Medicine at Brigham and Women's Hospital and professor of microbiology and molecular genetics at Harvard Medical School (HMS), and Sarkis Mazmanian, HMS instructor in microbiology and molecular genetics, both at the Channing laboratory, reports that Bacteriodes fragilis aids immune system development.

Mammals contain approximately a thousand species, and one trillion cells, of bacteria to every gram of intestinal contents. The team studied germ-free mice and found that these mice have fewer CD4+ T cells in their immune system. When B. fragilis colonized the mice, their CD4+ T cell levels were restored.

Another team in Kasper's lab previously announced that T cells could recognize certain bacterial carbohydrates as antigens. Kasper and Mazmanian found that if the mice were colonized with a strain of B. fragilis that lacked the carbohydrate polysaccharide A (PSA), the bacteria could no longer restore T cell levels in the mice.

The team found that PSA induces the Th1 subset of T cells. The immune system relies on a balance between these cell-mediated responses and antibody-mediated, or Th2, responses. Kasper said that mice and humans raised in sterile environments have immune systems skewed toward Th2 responses. If bacterial factors like PSA are necessary for development of the Th1 arm of the immune system, it would reinforce that bacteria is essential for immune function.

Novel combination overcomes drug-resistant multiple myeloma cells

70652986 — Mon, 26 Mar 2007 06:20:05 -0400

The researchers hope to move rapidly to clinical trials of the therapy, a combination of the drug Velcade and an experimental compound that was designed by researchers at the Broad Institute of the Massachusetts Institute of Technology and Harvard University.

The report demonstrates that the combination was more than twice as effective as either drug alone in killing resistant cells from patients' bone marrow.

"This is not just another drug - this is a whole new approach to treating multiple myeloma," said Kenneth Anderson, M.D., senior author of the paper.

Velcade is the first in a class of so-called proteasome inhibitors, which destroy cancer cells by blocking the proteasome, a disposal mechanism that rids the cell of abnormal proteins. Cells in which the proteasome is jammed eventually commit suicide, triggered by the accumulation of proteins, explains Anderson.

However, many cancer cells are resistant to proteasome inhibitors like Velcade. Recent studies have revealed an alternative protein-disposal complex, the aggresome, that may take over enough of the job when the proteasome falters to allow the cells to survive.

Therefore, the Dana-Farber researchers suggested that blocking both protein disposals at once might get around this resistance mechanism. Scientists led by one of the study's authors at the Broad Institute designed a drug that blocks an enzyme critical to the aggresome's ability to function.

These highly promising results, wrote the researchers, "provide the framework for clinical trials designed to enhance sensitivity and overcome resistance to bortezomib [Velcade], thereby improving patient outcome in multiple myeloma."

TB gene identified

50443248 — Tue, 24 Jul 2007 15:35:01 -0400

As many as one out of three people in the world are infected with the bacteria that causes tuberculosis, public health experts estimate. That could lead to a global plague were it not for the fact that only one out of 10 infected people actually develops the disease.
Still, TB is a major global health problem, particularly in developing countries. It sickens 8 million additional people each year, of which 2 million will die. So if scientists could find out what is going on in the bodies of the other nine people, they might be able to save millions of lives and avoid a great deal of suffering.

Broken hearts may mend after all

70652986 — Mon, 26 Mar 2007 06:18:30 -0400

Although adult muscle cells become inflexible after differentiation, these cells temporarily loosen the structure to divide in fetal development. Mark T. Keating found that in some lower vertebrates, heart tissue regenerates without the scarring seen in mammals. This seems to occur by proliferation of existing cardiomyocytes, not stem cells.

Felix Engel, an HMS research fellow in Keating's lab, set out to accomplish this in mammals. Engel first identified a growth factor that could specifically stimulate cardiomyocytes.

T cell misfits may spell autoimmunity

70652986 — Mon, 26 Mar 2007 06:18:08 -0400

For a would-be T cell, the journey from cradle to grave is likely to be brief. After leaving the bone marrow, the immature immune cell travels directly to the thymus, where it undergoes a winnowing process. To become a mature T cell, it must learn to attack alien proteins and not those peptides produced by the body. Precursors that fail this task -- because they have a strong affinity for self-peptides -- are eliminated. But occasionally an autoreactive T cell will slip by and travel to the periphery, where it can cause disease. In multiple sclerosis, for example, T cells leave the thymus, travel to the brain, and attack a protein in the myelin sheath surrounding nerve fibers. Researchers have wondered how the rogue T cells are able to avoid elimination. It now appears that autoreactive T cells can disguise their presence by altering the way their receptors interact with their target. Kai Wucherpfennig, a Harvard Medical School associate professor of neurology at the Dana Farber Cancer Institute, and colleagues revealed the trick by capturing and crystallizing a T cell receptor. Taken from a patient with multiple sclerosis, the receptor was caught in the act of binding. This is the first time a human autoreactive T cell receptor has been crystallized and imaged. The findings appear in the April 10, 2005, Nature Immunology.

TB susceptibility gene identified

70652986 — Mon, 26 Mar 2007 06:17:55 -0400

As many as one out of three people in the world are infected with the bacteria that causes tuberculosis, public health experts estimate. That could lead to a global plague were it not for the fact that only one out of 10 infected people actually develops the disease. Still, TB is a major global health problem, particularly in developing countries. It sickens 8 million additional people each year, of which 2 million will die. So if scientists could find out what is gong on in the bodies of the other nine people, they might be able to save millions of lives and a great deal of suffering. Part of the problem involves environmental factors such as poverty, stress, malnutrition, and companion diseases like AIDS.

New findings about protection against pneumococcal disease

70652986 — Mon, 26 Mar 2007 06:20:00 -0400

Before the advent of the pneumococcal vaccine, known as Prevnar, S. pneumoniae caused millions of ear infections each year, half a million episodes of bacterial pneumonia, and life- threatening cases of meningitis and bacteremia. Prevnar triggers recipients' immune systems to produce "anticapsular antibodies." However, Prevnar doesn't work well in the developing world, and it is expensive and difficult to manufacture. Moreover, in several studies, use of pneumococcal conjugate vaccines caused non-vaccine strains to become more common, suggesting that Prevnar could eventually become ineffective even in the U.S.

Lipsitch and Malley first conducted epidemiologic studies in unvaccinated toddlers in the U.S., Israel, and Finland, and the incidence of invasive disease from most pneumococcal strains fell by nearly half between one and two years of age. Yet anti- capsular antibody concentrations increased only slightly.

Searching for what caused these results, Malley and Lipsitch were able to elicit long-lasting immunity to pneumococcus in mice independently of any antibodies. When the mice were exposed to live pneumococci, or to a whole-cell vaccine developed in Malley's lab, they were immune to pneumococcal colonization, regardless of their ability to make antibodies. Moreover, mice exposed to a single pneumococcal strain became immune not just to that strain and others. The immunity appeared to arise from an effect on the immune system's CD4+ T-cells.

Their findings suggest that while antibodies protect sufficiently against pneumococcal disease, they may not represent the natural mechanism of protection.

The whole-cell vaccine could protect against all pneumococcal strains, Malley says, and would be a boon for the developing world because it is inexpensive, covers all pneumococcal strains, and does not require refrigeration.