New research at the Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies could result in a treatment against type 1 diabetes that has long-term efficacy and removes the need for insulin injection.
The authors plan to carry out a clinical trial with human patients at Seattle Children’s to test the treatment’s merits.
No more friendly fire
“What started as a dream is now within reach,” said Dr. David Rawlings, director of the center and corresponding author of the paper.
“My hope is that our research will lead to a new treatment that turns off the destructive immune response leading to the development of type 1 diabetes in children.”
Insulin production is handled by islet cells in the pancreas. Malfunctions in our bodies’ regulatory T cells (Treg) can cause the immune system to see them as threats, and attack. Treg cells work to organize and control effector T cells, which are the ones who actually carry out the attacks.
If enough of these cells are damaged, the pancreas becomes unable to regulate glucose levels in the blood, causing the early symptoms of type 1 diabetes such as frequent urination, unquenched thirst, insatiable hunger, and extreme fatigue. Current treatments require daily insulin injections, without which the disease can become fatal.
In a bid to find a treatment that doesn’t require the logistics of insulin production and supply, the team details how Treg cells of patients can be genetically engineered to function like their normal counterparts. Their approach targets the FOXP3 gene, which governs the process by which T cells can mutate into Treg cells.
In theory, once injected back into a patient, these cells (‘edited regulatory-like T cells’, or ‘edTreg’) should enter the pancreas and help keep the immune system in check.
The team notes that these edTreg cells look very similar to natural Treg ones, and that they behaved like them during tests in tissue samples and on animal models. They are currently working to start a phase 1 clinical trial of their therapy.
“This data offers the first proof that engineering by way of turning on FOXP3 is sufficient to make a functional Treg-like cell product,” said Dr Rawlings. “Not only is it a landmark research finding, but it’s directly translatable to clinical use.”
While all of this is going on, the authors are further refining the efficiency of their treatment and to devise a way to make edTreg cells target the pancreas directly.
The paper “Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function” has been published in the journal Science Translational Medicine.
On Tuesday, Australian researchers reported that they have successfully mapped the human body’s immune response to the coronavirus.
This is the first time anyone has mapped the general immune response of our bodies against the new virus, with potentially huge implications for the discovery of a cure. The findings were made from blood samples taken from a COVID-19 patient that was hospitalized with moderate symptoms.
How to heal
“We saw a really robust immune response that preceded clinical recovery,” Katherine Kedzierska, from the University of Melbourne’s Peter Doherty Institute for Infection and Immunity, told AFP.
“We noted an immune response but she was visually still unwell, and three days later the patient recovered.”
By establishing a baseline condition for patients with moderate cases of the disease, the team explains, we can start piecing together what’s different or missing in patients who become fatally ill.
The team says that their findings have two important applications. First, it will allow virologists to develop a vaccine, as vaccines aim to replicate the body’s natural immune response to viruses. They identified four distinct groups of immune cells in the blood of the COVID-19 patient during recovery, which is “very similar to what we see in patients with influenza,” according to Kedzierska. This is particularly exciting as we do have a broadly-effective influenza vaccine.
Until then, the findings could also help authorities better screen for infected individuals, and make more reliable predictions about at-risk groups in future outbreaks. The immune system markers identified in this study could, at least in theory, also be used to predict which patients will develop a mild case of the disease, and which are at risk of developing a more severe case.
Most COVID-19 deaths were recorded in elderly patients or those who had preexisting medical conditions, most notably heart disease and diabetes. Kedzierska said that more research is needed to understand why but, so far, children seem to avoid infection and show few or no symptoms after contracting the virus.
Hopefully, the findings of this study will be translated into an efficient cure or vaccine as soon as possible.
The paper “Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19” has been published in the journal Nature Medicine.
As news of the novel coronavirus — dubbed “COVID-19” by the World Health Organization — makes headlines as it spreads through China and the rest of the world, most attention has been directed towards prevention and quarantine. While properly washing your hands and avoiding crowds is a good idea if you live near an area that has reported cases, it’s important to also take steps to boost your immune system in case you actually come in contact with the virus so the body can effectively fight back.
The immune system is designed to fight off infection and disease. It has a number of ways to detect and destroy anything it recognizes as foreign to your body, including bacteria, viruses, fungi, parasites or unhealthy cells such as cancer cells.
Viruses need the cell machinery in order to produce their own proteins. They are intracellular parasites that can only replicate inside cells, which is one of the reasons they’re not considered to be alive. The most effective mechanisms of the innate response against viral infections are mediated by interferon and by the activation of natural killer (NK) cells.
The strength of the immune system varies from person to person and, what’s more, from day to day because its ability to fight off infection fluctuates depending on many factors. Here are a couple of things you can do to keep your immune system in check during the COVID-19 outbreak.
With all the daily headlines sowing doom and gloom about the novel coronavirus, it’s easy to stress over it. Some are so panicked that they’ve begun stockpiling basic goods and food. It’s a good idea to be prepared for any major emergency — and this includes a viral outbreak — however bear in mind that stress hormones tax the immune system, making its response to viral infections less effective.
In short supply, the stress hormone cortisol can boost immunity by limiting inflammation. But, once it crosses a certain threshold, too much cortisol in the blood opens the door for more inflammation. Stress also negatively impacts the production of lymphocytes — the white blood cells that are the body’s first line of defense against infection — putting you at risk of viral disease.
During this particularly stressful period, try not to panic because you’ll only make matters worse. Remember, the effects of stress are cumulative, meaning even ordinary, day-to-day activities can eventually lead to more serious health issues.
“We already know that, for the vast majority of people that are already healthy, this is really more of an inconvenience to a lot of them than something that can be fatal or life-threatening,” said Dr. Caroline Sokol, an immunology researcher at Massachusetts General Hospital.
To relieve stress, take breaks when you feel burned out and try to practice some relaxation techniques such as mindfulness, meditation, or positive thinking.
Exercise but don’t go overboard
Regular exercise promotes cardiovascular health, lowers blood pressure, helps control body weight, and offers protection against diseases. Exercise also improves blood circulation, allowing immune system cells to move through the body more freely and do their job more effectively.
Although scientists have yet to establish a direct link between exercise and immune system health, it’s reasonable to presume that moderate regular exercise can help prevent disease by promoting overall health.
However, intense exercise can cause inflammation in the body that may send the immune system into overdrive. So, try not to take things overboard especially during times of seasonal viral outbreaks.
Eat a balanced diet with fruits and vegetables
The immune system is the body’s natural defense system, and like any army, its warriors need sustenance. It’s rather well established that people who live in poverty and are malnourished are more vulnerable to infectious diseases.
Although there are have been few studies that tie the effects of nutrition directly to the development of infectious diseases, there is evidence pointing to the fact that various micronutrient deficiencies — such as those of zinc, selenium, iron, copper, folic acid, and vitamins A, B6, C, and E — can alter the immune response in animals.
Make sure you eat a balanced diet with fruits and vegetables in order to receive the right proportion of micronutrients.
greater susceptibility to infections such as pneumonia and influenza;
more severe and longer-lasting illnesses;
lower levels of protective antioxidants (such as vitamin C), in the blood.
Get enough sleep
Studies show that people who don’t get quality sleep or enough sleep are more likely to get sick after being exposed to a virus.
When we sleep, the body releases proteins called cytokines while sleep deprivation decreases their production. Cytokines are paramount during times of infection or inflammation. What’s more, the production of antibodies and immune cells is reduced when you don’t get enough sleep.
The optimal amount of sleep for most adults is between 7 and 8 hours. However, school-aged children and teenagers might need up to 10 hours of sleep.
A note on supplements. Although you’ll find bottles of pills and herbal supplements claiming to promote immunity or otherwise boost the immune system, there is no evidence that they actually bolster immunity.
Measles is a highly contagious virus that initially causes a runny nose, sneezing and fever and later leads to a blotchy rash starting on the face and spreading to the rest of the body. The majority of the people infected will recover, but measles can cause diarrhea and vomiting, which can lead to dehydration, middle ear infection (otitis media), which can lead to hearing loss, or pneumonia or potentially fatal encephalitis (swelling in the brain).
When people get an infection, their immune system produces antibodies to fight the infection. After the body gets rid of the infection, special immune cells remember that specific pathogen and help the body mount a faster defense if that same pathogen invades the body again. But not with measles. The virus reboots children’s immune system and the “amnesia” makes them vulnerable to other pathogens that they might have been protected from a previous infection.
In one study [M.J. Mina et al., Science, 366:599–606, 2019], measles infection in unvaccinated children in a community in the Netherlands was associated with up to a 70% decline in antibodies to other pathogens following infection. After cases of severe measles, unvaccinated children lost a median of 40% (range 11-62%) of their already existing pathogen-specific antibodies and after a case of mild measles, children lost a median of 33% (range 12-73%) of these pre-existing antibodies.
On the other hand, kids vaccinated retained over 90% of their antibody repertoires over the same period. The researchers examined blood from 77 unvaccinated children infected with measles in the Netherlands during a 2013 outbreak and compared these samples with the blood of 115 uninfected children and adults using the VirScan system, a tool that detects antiviral and antibacterial antibodies in the blood. Samples were taken prior to and after measles infection.
The team found that rather than a simple loss of total IgG, the most common type of antibody found in blood circulation, there is a restructuring of the antibody repertoire after measles. This is the first study to measure the immune damage caused by the virus and is further evidence for the “immune amnesia” hypothesis (that by depleting antibody repertoires, measles partially obliterates immune memory to previously encountered pathogens).
The same investigators also infected macaques with measles and monitored their antibodies against other pathogens for five months. The measles-infected monkeys lost 40–60% of their antibodies against pathogens they have previously encountered suggesting that measles infection wipes out long-lived plasma cells in the bone marrow that can create pathogen-specific antibodies.
A separate, independent team published a related study [V. N. Petrova et al., Sci Immunol, 4:2019] showing that measles infection causes incomplete reconstitution of the naïve B cell (not exposed to an antigen) leading to immunological immaturity and compromised immune memory to previously encountered pathogens due to depletion of memory B lymphocytes that persist after measles infection. The study provides a clear biological explanation for the observed increase in childhood deaths and secondary infections several years after an episode of measles.
These two new studies emphasize the importance of measles vaccination and suggest that given these findings, booster shots against other illnesses, such as hepatitis or polio, may be necessary for children infected with measles.
In 2017, the World Health Organization (WHO) reported 110 000 measles deaths globally, mostly among children under the age of five. The actual number of people infected with measles is most probably higher given that the WHO only collects data on cases confirmed through lab testing or clinical visits excluding thousands who do not seek medical attention.
With the global trend of vaccine hesitancy, skeptical parents are refusing to get their children vaccinated due to false concerns about their safety. These 2 new studies add strong evidence and undoubtedly confirm what scientists and public health experts have known all along: measles bad, vaccines good. This time let’s remember… let’s not have amnesia that measles can cause immune amnesia.
Exposure to wildfire smoke may alter the immune system for years, new research found, as the tiny particulate matter in the smoke that penetrates into the lungs and into the bloodstream could linger for a long time.
When exposed to wildfires, people are also inhaling noxious fine particles measuring less than 2.5 microns, or a fifth the size of a particle of dust or pollen. Researchers have had a hard time quantifying exposure to those tiny particles.
A new study, published in the journal Allergy, found exposure to high levels of that tiny particulate matter, abbreviated as PM2.5, impairs the immune system of children. The researchers tested the blood of 36 children exposed to wildfire smoke blown into Fresno in 2015.
In their results, they found changes in a gene involved in the development and function of T cells, an important component of the immune system. The alteration made the gene less capable of producing T regulatory cells, potentially putting the children at greater risk of developing allergies or infection.
“T regulatory cells act as peacekeepers in your immune system and keep everything on an even keel,”Mary Prunicki, an allergy researcher and lead author, told WIRED. “You have fewer of these good, healthy immune cells around when you’re exposed to a lot of air pollution.”
As with wildfires, controlled fires to clear out underbrush, known as prescribed burns, also can cause health effects. Thirty-two children exposed to smoke from prescribed burns had immune changes, too, but the effect wasn’t as strong as it was for children exposed to wildfire smoke, the study showed.
The research did not follow those children to see if their altered immune systems led to worse health outcomes, but an ongoing study at the University of California, Davis, raises some similar concerns. This one focused on rhesus macaques that live in an outdoor enclosure at the California National Primate Research Center and were exposed to 10 days of PM2.5
At three years of age, researchers examined 50 monkeys that had been exposed to wildfire smoke. They produced less of an immune-related protein as compared to monkeys not exposed to smoke as babies. That protein triggers inflammation to fight pathogens. A closer examination o revealed immune-related genetic changes as well.
“Clearly, the toxicants in air pollution are having a permanent effect on the DNA of immune cells,” Lisa A. Miller, principal investigator, told WIRED. “It’s a change that stays with that cell for its entire life.”
The National Interagency Fire Center predicts an “above normal” potential for wildfires this summer for Northern California. People can take precautions to limit their exposure when wildfire smoke blankets their area. Some cities provide “clear air centers” like a wildfire version of the evacuation shelters used during hurricanes.
Remember what your mom used to say about not getting dirty when you play outside? Turns out she might be wrong. A new study out of Ohio State University (OSU), published in in the journal Frontiers in Immunology has found that getting up close — and a little dirty — with farm animals just might help us fend off illness.
The OSU researchers found that bacteria and other microbes found in the stomachs and intestines from rural Amish babies were far more varied than those from urban areas. The experiment, which is a first of its kind, discovered evidence of how a healthier gut microbiome could lead to a more robust evolution of the respiratory immune system.
“Good hygiene is important, but from the perspective of our immune systems, a sanitized environment robs our immune systems of the opportunity to be educated by microbes. Too clean is not necessarily a good thing,” said the study’s co-lead author Zhongtang Yu, a professor of microbiology in OSU’s Department of Animal Sciences and a member of the university’s Food Innovation Center.
In the study, Yu and his team collected fecal samples from 10 babies in Ohio, all approximately six months to a year old. Five of the babies came from rural homes which raised farm animals. The five urban babies were from the mid-sized city of Wooster. None of those had any known contact with livestock.
Based on the infants’ exposure to animals, and the fact that Amish tend to live a less decontaminated life than urban dwellers, the researchers expected a difference in gut microbes. However, what they had really wanted to know was how the differences might affect the development of the child’s immune system, which would prepare the babies to ward off diseases as well as allergy resistance and other immune-system complications.
Previous comparative studies of the Amish to urban populations have lead to a theory called the “hygiene hypothesis,” an idea that ultra-clean modern life — think antibacterial soap and hand sanitizer — has led to an increase in autoimmune and allergic diseases.
To study the babies gut microbes, the researchers used fecal transplants to colonize the guts of newborn pigs.
“The priming of the early immune system is much different in Amish babies, compared to city dwellers,” said Renukaradhya Gourapura, a co-lead author of the study.
“We wanted to see what happens in early immune system development when newborn pigs with ‘germ-free’ guts are given the gut microbes from human babies raised in different environments,” Gourapura said.
“From the day of their birth, these Amish babies were exposed to various microbial species inside and outside of their homes.”
What they found was a positive relationship between the diversified Amish microbes and a more-robust evolution of immune cells, particularly lymphoid and myeloid cells in the intestines.
A recent study published in Nature by scientists at the Weizmann Institute of Science has even shown that intestinal microbes, collectively termed the gut microbiome, may affect the course of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease.
Scientists announced that an experimental gene therapy may have cured babies of a rare genetic disorder, commonly known as “bubble boy disease,” which causes male babies to be born with little or no immune system.
A two-year-old patient who was treated with the new gene therapy and his mother. Credit: St. Jude.
The genetic disorder called X-linked severe combined immunodeficiency (XSCID) and colloquially referred to as “bubble boy” disease, is caused by mutations in a gene on the X chromosome called IL2RG. The mutation causes male babies to be born without the capability of producing immune cells, making those affected highly susceptible to life-threatening infections by viruses, bacteria, and fungi. Even catching a common cold can be fatal. Unless properly diagnosed and placed in a sterile environment, most individuals born with XSCID die within 2 years.
The rare condition that affects only 40 to 100 babies each year in the United States became widely known to the public from news and a 1980s movie about David, nicknamed the Boy in the Bubble. After David’s brother died of the same disease, doctors placed him in a plastic isolation unit that sheltered him from the outside world. He basically lived in a plastic bubble for nearly 13 years until he died in 1984 following an unsuccessful bone marrow transplant — at the time, his only chance at restarting his immune system.
Bone marrow transplant is still the most effective therapy for XSCID, however, the procedure is risky and requires a match from a sibling. In 1990, a form of SCID became the first human disease treated by gene therapy when scientists transferred a normal gene into the defective white blood cells of two young girls. These patients are still alive today and continue to participate in on-going studies. However, XSCID, the version that only affects males, has proved a lot more difficult to treat — until now.
Researchers at St. Jude Children’s Research Hospital and the National Institute of Health (NIH) performed an experimental therapy on 8 children, aged 2 months to 14 months, who could not find a donor match for their bone marrow transplant. The research team engineered a lentivirus vector from a de-activated HIV virus, which also included insulators that blocked the activation of certain genes in order to prevent leukaemia — a side effect of a previous gene therapy experiment. Bone marrow was collected from the infants, which then received 2 days of low-dose busulfan chemotherapy in order to make space for new cells to grow. The bone marrow with the engineered virus was then reinfused into the baby boys.
Within 3 months, immune cells were present in the blood of all but one patient, which had to undergo a second dose of therapy. All three main types of immune cells (T-Cells, B-cells, and natural killer cells) were produced. What’s more, most patients responded to vaccination and now seem to be living a normal life.
“A diagnosis of X-linked severe combined immunodeficiency can be traumatic for families,” said Anthony S. Fauci, director of National Institute of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID). “These exciting new results suggest that gene therapy may be an effective treatment option for infants with this extremely serious condition, particularly those who lack an optimal donor for stem cell transplant. This advance offers them the hope of developing a wholly functional immune system and the chance to live a full, healthy life.”
Although it may be still early to claim that this procedure is a cure, the fact that all three types of immune cells were restored suggests that this may be the case. It has now been more than two and a half years since the treatment began and there is no indication of leukaemia in the patients. The researchers are now still closely monitoring the children to see how durable the treatment is and to catch any signs of long-term side effects.
“The broad scope of immune function that our gene therapy approach has restored to infants with X-SCID — as well as to older children and young adults in our study at NIH — is unprecedented,” said Harry Malech, chief of the Genetic Immunotherapy Section in NIAID’s Laboratory of Clinical Immunology and Microbiology. “These encouraging results would not have been possible without the efforts of my good friend and collaborator, the late Brian Sorrentino, who was instrumental in developing this treatment and bringing it into clinical trials.”
The researchers at St. Jude say they might use the same strategy for other genetic disorders, such as sickle cell disease.
Using cutting-edge microscopy imaging, researchers discovered — and filmed — the ‘sensors’ macrophage cells use to detect pathogens. The research might also yield one of the most powerful tools to date in the fight against cancer.
Image credits University of Queensland / Youtube.
Macrophages form the first line of defense in our immune systems, patroling tissues throughout our bodies and guarding the bits susceptible to infection. Once a macrophage encounters something that doesn’t wear the protein tags of healthy human cells — such as cellular debris, pathogens, cancer cells, or foreign substances — the cell wraps around it and proceeds to digest it.
Still, despite decades of research, we still barely understand how macrophages — and their other white cell relatives — work. In an effort to patch our grasp of these mechanisms, a team from the University of Queensland (UQ) used cutting-edge microscopy techniques to film macrophage cells.
Their research led to the discovery of structures known as “tent-pole ruffles”, which underpin the cells’ functions. The same structures, the team writes, may help us find a new and very powerful tool against cancer.
If you can’t beat them, eat them
“It’s really exciting to be able to see cell behaviour at unprecedented levels of resolution,” says co-author Adam Wall, a researcher in molecular bioscience at UQ.
“This is discovery science at the cutting edge of microscopy and reveals how much we still have to learn about how cells function”.
The ruffles are located on the surface of macrophages, a specific type of white blood cell that directly engages pathogens and other undesirables in our bodies. Tent-pole ruffles underpin their function, the team writes, by allowing the cells to sample their surrounding fluids for potential threats.
How tent-pole ruffles work — video below. Image credits Nicholas D. Condon et al., 2018, JCB.
They take the name from their shape and work similarly to our sense of taste or smell: the ruffles extend from the cell’s body and — using a special membrane strung between the poles — gather relatively large volumes of fluid that are then sampled for chemical markers. This process is known as ‘macropinocytosis’. If any molecules from a foreign entity are detected, the cells move towards the source and prepare to engage.
Tent-pole ruffles are exceedingly small. Their discovery was only made possible by a new imaging technology known as ‘lattice light sheet microscopy’. The technique can capture tiny structures in a matter of seconds, generating stunning 3D renditions with very high precision.
“This imaging will give us phenomenal power to reveal how cell behaviour is affected in disease, to test the effects of drugs on cells, and to give us insights that will be important for devising new treatments,” says study supervisor Jenny Stow, a deputy director of research in molecular bioscience at UQ.
It’s a very fortunate development. The research helps us better understand how our immune systems scrub the body clean of pathogens, but it also points to a way to cripple cancer cells. These latter cells use the process of macropinocytosis to capture nutrients, not to probe their environment like the macrophages. Apart from that, the process works largely the same — tent-pole ruffles extend, the membranes capture field, and nutrients are absorbed.
In theory, then, if researchers can figure out how to destroy or inactivate the tent-pole ruffles of cancer cells, we could simply starve them out.
The team plans to continue using lattice light sheet microscopy to probe the natures of other human immune system cells.
The paper “Macropinosome formation by tent pole ruffling in macrophages” has been published in the Journal of Cell Biology.
Many so-called health gurus or experts have perpetuated the notion that strenuous exercise weakens the immune system. A new study has debunked this myth, showing that endurance sports can actually boost the immune system.
The widespread belief that endurance sports increase the risk of infection can be traced back to a small study carried out in the 1980s at the Los Angeles Marathon. Researchers had asked athletes competing in the marathon whether they had any symptoms of infection in the days and weeks after the race and because many did, the notion that this happens across the board simply stuck.
In a new study, researchers at the University of Bath have reinterpreted the findings of the 1980s study based on the fundamental principles of immunology and exercise physiology. The authors explain that challenging exercise such as running a marathon changes the behavior of immune cells in two distinct ways. Initially, during the physically intensive act, the number of immune cells in the bloodstream can skyrocket up to 10 times their normal amount — this is especially the case for ‘natural killer cells’, which directly tackle infections. After the exercise, however, some immune cells decrease substantially in the bloodstream, sometimes falling below the pre-exercise baseline. This effect can last for several hours.
This fall in immune cells was previously interpreted as the body’s immune-suppression response to strenuous exercise. The British researchers, however, stress that this does not mean that the cells have been ‘lost’ or ‘destroyed’, but rather that they’ve moved to other more vulnerable sites of the body where infections are most common, such as the lungs.
According to Dr. John Campbell from the University of Bath’s Department for Health, there are three pieces of evidence to indicate that the immune cells are not actually destroyed. The first and most obvious reason is that the cells return to normal levels within several hours, which far too quickly for them to be replaced by new cells. Secondly, previous studies showed that it is not only possible but also natural for cells to leave the bloodstream and travel to other sites in the body. Lastly, studies on mice where immune cells were tagged and labeled showed that, following exercise, these tagged cells accumulated in the lungs, as well as other places that are susceptible to infections.
“It is increasingly clear that changes happening to your immune system after a strenuous bout of exercise do not leave your body immune-suppressed. In fact, evidence now suggests that your immune system is boosted after exercise – for example, we know that exercise can improve your immune response to a flu jab,” Campbell said.
Co-author, Dr James Turner added, “Given the important role exercise has for reducing the risk of cardiovascular disease, cancer and type II diabetes, the findings from our analysis emphasise that people should not be put off exercise for fear that it will dampen their immune system. Clearly, the benefits of exercise, including endurance sports, outweigh any negative effects which people may perceive.”
The authors stress that while a heavy duty workout itself will not increase the likelihood of catching an infection, it’s possible that other factors involved in the act of exercising might. For instance, attending a sports event where large crowds of people gather can expose people to airborne infections. Other factors, like eating an inadequate diet, getting cold and wet, and psychological stress, have all been linked to a greater chance of developing infections.
A class of antibodies known to attack the body itself could prove to be the last line of defense against threats that the immune system can’t engage.
Rat hippocampus stained with NeuN antibodies (unrelated to this study, green), myelin basic protein (red), and DNA (blue). Image credits EnCor Biotechnology Inc. via GerryShaw / Wikimedia.
In a world first, researchers from Sydney’s Garvan Institute of Medical Research report that a population of ‘bad’ antibodies — which are usually inactivated, because they tend to attack the body’s tissues and cells — form a vital last line of defense against invading microbes.
The group of antibodies is usually seen in an inactive form in the body — which prompted most researchers to consider them a relic of our immune systems, discarded and permanently decommissioned by our bodies when they outlived their usefulness. And, at least on first glance, there seems to be a very valid reason for this: the antibodies, when active, attack the body’s own tissues and can lead to autoimmune diseases.
New research shows that the antibodies’ unbridled aggression may actually be by design. The study shows that they become active when a disease overcomes the immune system’s other defenses, or when pathogens try to imitate the body’s cells to stay safe. The antibodies also go through a rapid genetic modification process upon activation, following which they no longer threaten the body. However, they do remain very good at killing pathogens that disguise themselves to look like normal body tissue.
“We once thought that harmful antibodies were discarded by the body — like a few bad apples in the barrel — and no one had any idea that you could start with a ‘bad’ antibody and make it good,” says Professor Chris Goodnow, who lead researcher.
“From these new findings, we now know that every antibody is precious when it comes to fighting invading microbes — and this new understanding means that ‘bad’ antibodies are a valuable resource for the development of vaccines for HIV, and for other diseases that go undercover in the body.”
Certain pathogens, such as Campylobacter or HIV, have evolved to appear almost identical to the body’s cell and can thus fly under the immune system’s radar. Even if detected, these adaptations ensure the viruses are protected, because our bodies systematically avoid using antibodies that are capable of binding (i.e. attacking) its own structures.
Goodnow’s previous research aimed at understanding how our immune systems recognize these threats — some 30 years ago, his search led to a group of mysterious antibodies hidden inside silenced ‘B cells’. These are the immune cells that don’t engage pathogens directly; rather, they’re more like advanced weapon factories, producing biochemical defenses and releasing them into the bloodstream. Unlike your more run of the mill B cells, however, the group his team identified produces antibodies that can pose a danger to the body — so they’re kept on standby, in a silenced state known as ‘anergy’.
“The big question about these cells has been why they are there at all, and in such large numbers,” Prof Goodnow says. “Why does the body keep these cells, whose antibodies pose a genuine risk to health, instead of destroying them completely, as we once thought?”
Goodnow’s new paper reports that these cells can, in fact, be re-activated to fight off threats other B cells can’t — but only after they’ve been genetically ‘re-tooled’ for the task.
Working with a preclinical mouse model, the team showed that this group of cells starts producing antibodies when they run into pathogens that appear highly similar to the body’s own cells. Before they engage, however, they go through tiny alterations in their DNA sequence — which, in turn, alter the antibodies’ behavior. This step is crucial: the new model of antibodies no longer attacks the body, but become up to 5000 times more effective in murdering the invaders, the team reports.
In the model they tested, this antibody retooling only involved three DNA changes in the genomes of the B cells. The first change prevented the compounds from binding to the body’s own cells, while the other two were solely aimed at increasing their ability to bind to the invader.
Schematic of an antibody’s structure. Image credits Mamahdi14 / Wikimedia.
In experiments carried out at the Australian Synchrotron, the team showed how these three DNA changes rearrange the structure of the antibodies (which use tip-like structures to bind to other cells or pathogens) to make them better stick to invaders. One change of note they report on is that the altered antibodies’ tips fit neatly on a nanoscale ‘dimple’ that’s present on the pathogens but not the body’s cells. Another important find is that these antibodies are actually super effective: the results, Goodnow noted, show that they “can be even better than those developed through established pathways”.
It’s important to note that, being drawn from observations on mouse models, the results may not be directly translateable to human biochemistry — although it likely is, further research will be needed before we can say for sure. Regardless, the team hopes their work will pave the way to new and improved vaccines based on these B cells — particularly against pathogens such as HIV, which the rest of the immune system can’t engage.
The paper “Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination” has been published in the journal Science.
People of African descent are thought to be partially protected against malaria thanks to a genetic variant. There now seems to be another far bigger advantage to the genetic variation, that is the development of immune cells better armed to fight infections.
A T helper cell – a type of T cell that play an important role in the immune system. Image via Pixabay.
After having a routine blood test, Mr. B found out that he had an unusually low count of immune cells called neutrophils. Neutrophils are white blood cells, which are particularly good at rapidly eliminating microbial pathogens. Yet, Mr. B is perfectly healthy and a new report published in Nature Immunology now indicates that his neutrophils may be even better armed for fighting specific infections. Mr. B was born in Ghana and like virtually all individuals of African ancestry, carries a specific genetic variation, a polymorphism, of a molecule called the Duffy antigen. This polymorphism has been linked with having innocuous low neutrophil counts.
The drastic effects of the Duffy antigen on neutrophils had long been puzzling scientists jointly working at the Ludwig Maximilian University Munich and the University of York.
“Individuals of African ancestry, who carry the polymorphism, lack Duffy antigen on their red blood cells, they are Duffy-negative” explains Rot, Chair of Biomedical Sciences at the University of York, and lead scientist of the study.
This protects them against a malaria parasite, which otherwise highjacks the Duffy antigen in order to invade red blood cells. The group of scientists now reveals that there is much more to the Duffy polymorphism than malaria protection. They studied bone marrow cells of mice, which were deficient in Duffy antigen.
“We found that the lack of this molecule had a profound influence on the stem cells and the very early development of immune cells, particularly the progenitor cells of neutrophils,” says Duchêne, group leader at the Ludwig Maximilian Univeristy Munich and first author of the study. “As a result of their changed development, mature neutrophils of Duffy-negative individuals carry more molecular “weapons” against infectious pathogens” says Duchêne.
The scientists also show that these distinctive neutrophils readily leave the blood stream, which explains the apparent lower numbers of neutrophils in the blood of Mr. B.
“Although an alternative “super-armed” immune system may be an advantage to fight infections, a stronger immune response may be detrimental in the context of chronic inflammation and autoimmune diseases” argues Rot.
Indeed, individuals of African ancestry are more susceptible to heart disease, stroke and several autoimmune and inflammatory diseases. This study comes as a serious warning to today’s genomic medicine, which aims to map disease traits with genetic variants based on 96% of participants from European descent. “Black lives Matter,” Rot likes to say. He hopes the findings will lead to “therapies specifically tailored to tackle diseases in individuals of African ancestry”. Mr. B too.
This is a guest post by Anne Rigby (photo below). Anne is a former Biologist, particularly fascinated by Immunology. She gets excited by new scientific ideas and hypotheses which challenge our current thinking.
Journal Reference: Duchene J et al. Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis. 2017. Nat. Immunol. doi:10.1038/ni.3763
Two new papers published in the journal Cell offer the first high-detail maps of the immune system cells which surround tumors.
Breast cancer cell seen under a scanning electron microscope. Image credits National Cancer Institute.
The data could help guide research into new targets for cancer therapies and pinpoint biological markers which can be used to determine the likelihood of patients to respond to particular therapies or when best to start administering them.
What type of cells surround a tumor and the way they respond to it (especially immune system cells which bunch up at its border and fight towards the core) usually makes or breaks immunotherapy aimed at fighting the disease. Recent advances in the ability to characterize those individual cells are now driving a push to catalog and learn more about how the cells impact the progression of tumors.
Act faster, use more data
The first of the papers was published by a team led by Bernd Bodenmiller, a systems biologist at the University of Zurich, Switzerland. The team mapped the body’s immune response for clear cell renal cell carcinoma, a form of kidney cancer. The researchers focused on two types of immune cells — T cells and macrophages. Both of them are involved in either increasing or suppressing the body’s immune response to a tumor by altering the proteins they express.
Bodenmiller’s team worked with samples from 73 patients with kidney cancer and 5 samples from healthy individuals as a control group. They analyzed 3.5 million cells looking at the expression of 29 proteins used to characterize macrophages, and 23 to characterize T cells.
They found that the T cell populations and those of the macrophages were more varied than previously believed. They also note that patients with a particular combination of T cells and macrophages tended to have fast-progressive cancers. All in all, their results shows that the current practice of looking only at one or two major proteins to determine the state of a T cell or macrophage falls very short of giving oncologists the full picture.
The second study was led by oncologist Miriam Merad of the Icahn School of Medicine at Mount Sinai, New York City. His team compiled an atlas of immune cells associated with early-stage lung cancer. By comparing healthy lung tissue and blood with tumor tissue, they found that immune cells in the vicinity of tumors start to alter themselves since the early stages of the disease. This suggests that cancer treatments which target the immune system can be employed from the start, without having to wait for more advanced stages of the disease.
Understanding how our immune systems change in response to cancer would let doctors tailor our interventions against the disease to work in tandem with our bodies — so work like that performed by these two teams is hugely important for patients. The studies themselves are too small to change how we go about treating cancer right now — but they offer a wealth of possibilities. As more researchers double-check the findings and add new data on the foundation these two papers set in the coming years, we’re likely to see cancer treatments becoming more and more personalized.
The first paper “An Immune Atlas of Clear Cell Renal Cell Carcinoma” has been published in the journal Cell. The second paper “Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses” has been published in the journal Cell as well.
Researchers have discovered why cancer cells are able to cloak themselves from the body’s immune system, allowing them to metastasize and spread throughout the body.
Cancer cells. Image credits National Cancer Institute.
Cancer is a terrible disease. Contrary to common-held beliefs, however, it’s not a modern disease, nor is it a human-only one. It arises from genetic defects in cells’ DNA. As the tumors develop, more and more mutations are added to the cells’ genetic code.
University of British Columbia scientists have discovered that through this process, cancerous cells lose the proteic pathway used to synthesize interleukein-33. IL-33 is an intermediary in a “warning flag” complex of proteins known as the major histocompatibility complex (MHC.)
MHC proteins coat diseased or malfunctioning cells so that white blood cells know to swoop in and recycle them — so, when the IL-33 protein disappears, malignant cells look like their ordinary, healthy counterparts to our immune system. Unattacked, they grow and spread out through the body — a step known as metastasis.
“The immune system is efficient at identifying and halting the emergence and spread of primary tumours but when metastatic tumours appear, the immune system is no longer able to recognize the cancer cells and stop them,” said Wilfred Jefferies, senior author of the study working in the Michael Smith Laboratories and a professor of Medical Genetics and Microbiology and Immunology at UBC.
The team found that IL-33 loss occurs in epithelial carcinomas — cancers of organ-lining tissues. This includes prostate, kidney, breast, lung, uterine, cervical, pancreatic, and skin — among many other — types of cancer. With help from the Vancouver Prostate Centre, they studied several hundred patients and found that people suffering from prostate or kidney cancers whose tumours didn’t produce any IL-33 had more rapid recurrence of the condition over a five-year period.
When treating metastatic cancers with the protein, the patients’ immune systems jump-started and began attacking the malignant cells. The group hopes that reversing the genetic processes which rids cancers of marker proteins such as IL-33 will make them visible as targets to white blood cells again.
“IL-33 could be among the first immune biomarkers for prostate cancer and, in the near future, we are planning to examine this in a larger sample size of patients,” said Iryna Saranchova, a PhD student in the department of microbiology and immunology and first author on the study.
Researchers have been desperately searching for an effective cure for cancer, with some success (see here and here). But finding a way to make our own immune system attack tumours would definitely revolutionize how we think about this disease in the future.
The full paper “Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33” has been published in the journalScientific Reports.
The CRISPR gene-editing technique has opened up a lot of doors in the scientific world – it has been used to cut out HIV genes from live animals and genetically modify human embryos. Although its benefits are indisputable, experiments such as the latter have caused controversy, as some believe that they bring us closer to changing what it means to be human.
Now, Chinese researchers from the Sichuan University’s West China Hospital have announced their plans to run a clinical trial where CRISPR will be used to modify human beings for the first time ever. In particular, the team plans to work on patients with lung cancer and turn off genes that encode a specific protein linked to a lower immune response.
Although China has come under scrutiny for their promotion of using gene-editing techniques on human beings, the new effort isn’t as controversial as the aforementioned study on human embryos. In fact, a federal panel gave the green light for a similar U.S. study back in June.
“Our goal is to develop a new type of immunotherapy using gene-editing technology that will enable the engineered immune cells to be more potent, survive longer, and thereby kill cancer cells more effectively,” the U.S. team said of their research.
The Chinese clinical trial is set to start next month and will gather T cells, which play a central role in human immunity, from patients with incurable lung cancer and conduct genetic modifications in these cells. These modifications will disable a gene that encodes the PD-1 protein, which has been shown to inhibit the immune response that protects healthy cells from attack.
After the T cells have been successfully modified and examined for editing errors, they will be allowed to multiply and then injected back into the patient’s bloodstream. Ideally, the edited cells will bolster the immune response of the lung cancer patient and aid it in attacking and killing tumor cells.
Thirty candidates are set to participate in the trial, although just one will be injected with a three dose regimen of edited cells, after which the team will monitor the patient for any positive and negative responses to the treatment before proceeding with further trials.
If you’ve always wanted a tattoo but never quite got around to it, now you have the perfect excuse: a study conducted by researchers from the University of Alabama, getting multiple tattoos can actually strengthen your immune system.
The first tattoo makes your immune system weaker, but the next ones help you get stronger.
Getting a simple tattoo lowers your immune system, at least temporarily. You’re injecting a foreign substance inside your body, and your organism gets a big confused and tries to fight it. But if you get more tattoos, it’s a bit like going to the gym. The first time is awful, and you’ll feel like crap. It’s not uncommon to feel quite drained after getting a tattoo. Dr. Christopher Lynn, UA associate professor of anthropology said:
“They don’t just hurt while you get the tattoo, but they can exhaust you,” Lynn said. “It’s easier to get sick. You can catch a cold because your defenses are lowered from the stress of getting a tattoo.”
“After the stress response, your body returns to an equilibrium,” Lynn said. “However, if you continue to stress your body over and over again, instead of returning to the same set point, it adjusts its internal set points and moves higher.” In other words, you’re getting stronger.
This was the theory, and Lynn rallied former UA graduate student Johnna Dominguez, and Dr. Jason DeCaro, UA associate professor of anthropology to test it.
Approaching volunteers at tattoo businesses in Tuscaloosa and Leeds, Dominguez surveyed them, gathering information on how many tattoos they got and the timeframe in which they got them. Then, they gathered saliva samples before and after. The researchers analyzed the samples, measuring levels of immunoglobulin A, an antibody that plays a critical role in the immune function of mucous membranes. Immunoglobulin A also regulates portions of our gastrointestinal and respiratory systems, and cortisol, a stress hormone known to suppress immune response.
“Immunoglobulin A is a front line of defense against some of the common infections we encounter, like colds,” Lynn said.
They found that levels of immunoglobulin A dropped significantly for people getting their first tattoo. But the immunoglobulin A decrease was less so among those receiving tattoos more frequently, Lynn said.
“People with more tattoo experience have a statistically smaller decrease in immunoglobulin A from before to after,” said Lynn. In a way, getting a tattoo is like taking your immune system to the gym.
The thymus is one of those under appreciated organs you just don’t hear much about. Sitting in your chest, just in front of your heart, the thymus is at its largest and most active during infancy and childhood. By adulthood, the thymus has shrunk to practically nothing, being mostly replaced by fat. It plays an important role in the health of your immune system, and is the location where certain immune cells, called T-cells, go to mature and develop properly.
The thymus is like a schoolhouse for T-cells where they learn important lessons, like “recognize these sets of proteins as part of our own body and don’t attack them, but attack anything you don’t recognize because it must be a foreign intruder”. It allows the immune system to develop what is known as Central Tolerance. Without central tolerance, we develop auto-immune disease, which is essentially your immune system fighting a civil war against other parts of your own body. Diseases like Lupus, Type 1 diabetes, Myasthenia gravis, and many others are autoimmune diseases with the immune system actively damaging some parts of the body. In Type 1 diabetes, for instance, the immune system targets your pancreatic islet cells for destruction, resulting in loss of your bodies ability to make insulin.
The thymus is an organ where T-cells mature, and may be a source of regulatory T-cells that have the potential to treat autoimmune disease.
It is also known that there are many varieties of T-cells, each with unique and important roles to play in immune function. One type of T-cell is known as the Regulatory T-cell or Treg. Tregs are special because they help to keep the other cells of the immune system from getting too wild and out of control (a recipe for autoimmune disease). They can go into an inflammatory situation where lots of immune cells are activated and ready to rumble, and tell those cells, “alright, everyone just calm down”, thereby suppressing the immune response. Some studies have show that Tregs can be infused into patients with autoimmune disease to help control their symptoms. They might even be a valuable way to suppress the immune system in people with an organ transplant, like a kidney or heart. Tregs are a way to use one part of the immune system to control other parts of the immune system – like fighting fire with fire – in the case of autoimmune disease.
These treatments, while promising, are still not fully evaluated and are not standard of care as of yet. One reason that not much research has been done using Tregs as a therapy is that they are hard to come by. They can be collected from the blood of donors, then grown in the lab to try to get enough cells for treatment, but the process is inefficient and doesn’t result in a large number of Treg cells.
This month in the American Journal of Transplantation, a team of Canadian researcher showed that discarded human thymuses are an excellent source of Tregs that can be harvested and used to treat a variety of immune mediated disease. So why would there ever be a discarded thymus? It turns out that when an infant is undergoing heart surgery, as might be done to correct a cardiac birth defect, the thymus is huge and in the surgeons’ way, and must be removed to gain access to the heart. This is true in infants where the thymus is very large compared to the heart, but not a problem in adults where the thymus has already atrophied to a tiny insignificant size.
Tregs can be identified and isolated based on unique protein markers on their cell surfaces such as CD25+,CD4+, and FOXP3. Other immune cells show different sets of markers making it possible to identify the different cell types, and select only the ones needed. The researchers found that they could identify and isolate many more Tregs from one discarded infant thymus, than could be generated from the blood of an adult donor. In fact, they could show that there are more Tregs in an infant thymus than are present in the entire circulation of an adult. They also found that the Tregs from discarded infant thymus function better compared to those recovered from the process of blood donation. It is thought that this might be due to the immaturity of Tregs coming from thymus versus blood, since those in the blood have been around longer and show other markers of cellular aging, such as shorter telomere length.
Perhaps if more Tregs become available from thymus harvesting, more clinical studies studies will be conducted that may hopefully find effective ways to treat autoimmune diseases that today are very difficult to control and create much suffering in the lives of so many people.
1. Am J Transplant. 2016 Jan;16(1):58-71. doi: 10.1111/ajt.13456. Epub 2015 Sep 28. Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells.
Dijke IE1,2, Hoeppli RE3, Ellis T1,2, Pearcey J1,2, Huang Q3, McMurchy AN3, Boer K4, Peeters AM4, Aubert G5, Larsen I1,2, Ross DB2,6, Rebeyka I2,6, Campbell A3, Baan CC4, Levings MK3, West LJ1,2,6.
A breakthrough research found that male and female mice use different cells to signal pain. This could explain why both more women suffer from chronic pain than men, and pain relief medication seems to respond differently in women.
Men and women respond to pain differently.
The international team of researchers set out to test a long-standing hypothesis: that the pain signal is transmitted to the brain from the site of injury or inflammation microglia – immune cells found in the brain and spinal chord. But when drugs were administered that inhibited the microglia cells, only the male mice showed reduce pain response. The female mice were completely unaffected, suggesting pain is transmitted via a different mechanism. The researchers hypothesis that T cell, fundamentally different immune cells, relay pain the female mice. This needs to be confirmed.
“Understanding the pathways of pain and sex differences is absolutely essential as we design the next generation of more sophisticated, targeted pain medications,” says co-senior author Michael Salter, a professor at the University of Toronto.
“We believe that mice have very similar nervous systems to humans, especially for a basic evolutionary function like pain, so these findings tell us there are important questions raised for human pain drug development.”
In 2009, single-sex studies of male animals outnumbering those of females 5.5 to 1. Prompted by a growing body of evidence that suggests males and females respond differently, the US National Institutes of Health issued a new policy which mandates preclinical research to study tissue from both sexes.
“For the past 15 years scientists have thought that microglia controlled the volume knob on pain, but this conclusion was based on research using almost exclusively male mice,” Mogil says. “This finding is a perfect example of why this policy, and very carefully designed research, is essential if the benefits of basic science are to serve everyone.”
Alec Falkenham, a 27-year-old PhD student at Dalhousie University in Halifax, has invented a special cream that will wipe out tattoos for good, without the pain and scaring expected today following laser surgery. Time to erase your ex-lover’s name off that shoulder… or keep it! Good or bad memories are what make you the person you are today, you shouldn’t be ashamed of that. Either way, soon enough you might have the means to make your own choice – one that doesn’t involve burning you skin.
A Norwegian teen named Stian Ytterdah got a McDonald’s receipt tattooed on his arm and became Internet famous for his bad decision. Credit: VG TV
Tattoos are permanent not because they’re inked too deep in the skin. The ink stays there because your immune system and the molecules that make the tattoo ink are constantly locked in a tug. As such, tattoos are actually permanent inflammations!
When a tattoo needle punctures the skin, it rips through the epidermis, the outer layer of skin, and spills ink in the dermis, the inner layer of skin which is flooded with blood vessels and nerves. With each penetration, the immune system is alerted there’s a wound going on and immune system cells are sent to the site. Some of these are macrophages which gobble up the ink in an attempt to clean the area. What’s left of the ink becomes absorbed by skin cells called fibroblasts. Most of the fibroblasts and macrophages alike become suspended in the dermis where they’re locked permanently. The dye in both cells show through the body which is why you can see your tattoo in the first place.
Falkenham’s works its magic by targeting those macrophages that stayed put and are embedded in the skin. New macrophages move in to consume the previously pigment-filled macrophages and then migrate to the lymph nodes, eventually taking all the dye with them. Eventually, these make it to the liver where they’re readied for excretion.
The student is not yet certain how many applications of the cream are necessary for a complete fade away. In fact, we’ve yet to see any pictures or demonstrations for that matter, but allegedly the cream has been tested on tattooed pig’s ears with success. It might sound too good to be true, but it might just work.
Currently, the best way to get rid of a tattoo is through laser surgery. Basically, lasers producing short pulses of intense light every 0.000000000001 seconds pass harmlessly through the top layers of the skin to be selectively absorbed by the tattoo pigment. This laser energy causes the tattoo pigment to fragment into smaller particles that are then removed by the body’s immune system. It is very painful, however. Those who have gone through it described the experience akin to hot specks of bacon grease on your skin or being snapped by a thin rubber band – constantly! Of course, not all pigments will be removed, far from it. What you get instead is a “nice” scar.
“When comparing it to laser-based tattoo removal, in which you see the burns, the scarring, the blisters, in this case, we’ve designed a drug that doesn’t really have much off-target effect,” Falknham said.
“We’re not targeting any of the normal skin cells, so you won’t see a lot of inflammation. In fact, based on the process that we’re actually using, we don’t think there will be any inflammation at all and it would actually be anti-inflammatory.”
Falknham is currently working with his University’s Industry Liaison and Innovation office to patent his technology and ready it for market production.
“Alec is a trail blazer in tattoo removal. He came to ILI with an idea, tangentially related to his graduate research, that had real-life applicability,” said Andrea McCormick, manager, health and life sciences at ILI in a news release.
“His initial research has shown great results and his next stage of research will build on those results, developing his technology into a product that can eventually be brought to market.”
Falkenham estimates a tattoo removal treatment will cost four cents per square centimetre, so a typical a 10-by-10-centimetre area would cost approximately $4.50 per treatment.
Australian scientists have cured nut allergy in 80% of the children taking part in a probiotic clinical trial. These children’s lives how now been transformed forever, with many more – child or adult – to follow soon. Nut allergy is lifelong and the most common cause of death from food anaphylaxis.
Peanuts – back on the menu
Image: Allergy Reliever
Peanuts are among the most common allergy-causing foods, and chances have it if you’re not allergic to peanuts, you know someone who is. Because their so dangerous for those allergic to them, many food manufacturers are mandated by law to visibly label peanut content even in those foods which you’d think don’t have any business with peanuts. The thing is, peanuts often find their way into things you wouldn’t imagine. Take chili, for instance: lots of producers thicken these with ground peanuts.
Here’s some useful trivia: peanuts aren’t actually a true nut, but a legume in the same family as peas and lentils. However, the proteins found in peanuts are similar in structure to those in tree nuts, so people with allergic to peanuts can also be allergic to tree nuts, such as almonds, Brazil nuts, walnuts, hazelnuts, macadamia nuts, pistachios, pecans, and cashews.
Our immune system is great at warding off infections, but when a person is allergic to nuts, the immune system overreacts to the proteins in these foods and treats them as “invaders”. This causes a severe allergic reaction called anaphylaxis in which chemicals called histamine are released in the body. Anaphylaxis may begin with some of the same symptoms as a less severe reaction, but then quickly worsen, leading someone to have trouble breathing, feel lightheaded, or to pass out. If it is not treated quickly, anaphylaxis can be life threatening. It’s also an allergy that haunts those afflicted all their lives, but a new groundbreaking research might prove to be a life raft.
Researchers gave about 30 allergic children a daily dose of peanut protein together with a probiotic (Lactobacillus rhamnosus) in an increasing amount over an 18-month period. At the end of the trial, 80% of the Aussie kids could eat peanuts without any reaction.
“Many of the children and families believe it has changed their lives, they’re very happy, they feel relieved,” said the lead researcher, Mimi Tang. “These findings provide the first vital step towards developing a cure for peanut allergy and possibly other food allergies.”
Of course, this doesn’t mean that their allergies were cured for life. It’s possible of course, but many follow-up studies are mandated to assess whether patients can still tolerate peanuts in the years to come.
“We will be conducting a follow-up study where we ask children to take peanut back out of their diet for eight weeks and test them if they’re tolerant after that,” according to Tang.
If you’re thinking about doing this treatment on your own at home – don’t.
“Some families might be thinking about trialling this at home and we would strongly advise against this. In our trial some children did experience allergic reactions, sometimes serious reactions.
“For the moment this treatment can only be taken under the supervision of doctors as part of a clinical trial.”
Researchers at the Max Planck Institute of Immunobiology and Epigenetics (MPI-IE) re-activated the expression of an ancient gene in mice. To their surprise, the gene in question which is dormant in all mammalian species caused the mice to develop fish-like thymus. The thymus is an organ of paramount importance to the adaptive immune system, but in this particular instance, the thymus produced not only T cells, but also served as a maturation site for B cells – a property normally seen only in the thymus of fish. So, what we’re seeing is a resetting of the immune system to a state similar to what it was like 500 million years ago, when the very first vertebrates began to emerge. By closely following how these gene works, the scientists hope to build a model that will explain how the thymus evolved during the past hundreds of millions of years.
An ancient immune system, today
T-cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections, and are essential to human immunity. These are matured by the epithelial cells in the thymus, but genetically-wise it’s the FOX1 gene that triggers their development. FOX1’s evolutionary ancestor is FOX4, an ancient gene that lies dormant in most vertebrates except jawed fish, such as cat sharks and zebra fish.
The team led by Thomas Boehm, director at the MPI-IE and head of the department for developmental immunology, activated FOX4 in mice. When both FOX1 and FOX4 are simultaneously activated, the researchers found the mouse thymus exhibited properties similar to those found in a fish. Coupled with previous findings, the results suggest that that thymus as we know it today in most vertebrates evolved from and was prompted by the FOX4 gene. Through an evolutionary gene duplication FOX1 was born. Initially both genes must have been active, until finally only FOXN1 was active in the thymus.
The normal mouse thymus (left) contains only a small fraction of B-cells (red). If the gene FOXN4 is activated, a fish-like thymus with many B-cells develops. Image: Max Planck
A surprising find was that not only T-cells developed in the thymus of the mice, but also B-cells. Mature B-cells are responsible for antibody production. In mammals, they normally do not mature in the thymus, but in other organs, such as the bone marrow.
Boehm says that it’s not yet clear whether the B-cell development is based on the migration of dedicated B-cell precursors to the thymus, or to maturation from a shared T/B progenitor in the thymus itself. Nevertheless, it’s remarkable how the researchers have uncovered a particular evolutionary innovation that occurred in an extinct species. Retracting evolutionary steps in our collective ancestral background might provide insights we dare not dream of.