New Delhi: Bird flu, also called avian influenza, has come as a double whammy for countries that are already fighting their biggest battle against Covid-19. Again, the sign and symptoms are related to the respiratory system only along with fever. Since there is not much clarity about its complications and other issues which patients can face, there is no one way to deal with this situation.
As per the available data and as a general rule of Ayurveda strength of diseases can be reduced by only good immunity. So, the best way to protect yourself from any kind of disease is to boost your immunity and follow a healthy lifestyle which can go beyond opting good eating habits. Daily routine, waking up early morning and sleeping on time are also part of a healthy lifestyle.
With work-from-home in place, people now-a-days tend to work over night resulting in a disturbed sleep cycle. Such lifestyles affect our immunity and various ‘doshas’ of the body, says Dr. Pooja Kohli.
“So, first of all we all need to follow a healthy lifestyle which includes a healthy meal on time, sound sleep, daily exercise & meditation, offering food for our mind as well as soul,” says Kohli who is the Vice President of Ayurveda Growth at NirogStreet.
To keep your immune system in shape and strengthen body’s fighting mechanism she suggests these simple yet impactful tips to follow.
Give that extra herbs touch: You can add a few herbs like Ginger, garlic, turmeric in your daily diet to avoid bird flu kind of infections. These herbs give strength to the body for fighting back and also protect our body from getting infected.
A study by Ludwig-Maximilians-Universitaet (LMU) in Munich researchers shows that putatively immature dendritic cells found in young children are able to induce robust immune responses. The results could lead to improved vaccination protocols.
Dendritic cells are a vital component of the innate immune system, which constitutes the body’s first line of defense against infectious agents and tumor cells. Their job is to activate the T-cell arm of the adaptive immune system, which confers specific and long-lasting protection against bacterial and viral infections.
Dendritic cells engulf and degrade proteins that signal the presence of invasive pathogens. The resulting fragments (antigens) are displayed on their surfaces. T cells bearing the appropriate receptors are then activated to seek out and eliminate the pathogen.
Newborns and young children have fewer dendritic cells than adults, and these juvenile cells also carry fewer antigen-presenting complexes on their surfaces. Based on these observations, immunologists have generally assumed that these cells are functionally immature.
However, new work published by a research team led by Professor Barbara Schraml at LMU’s Biomedical Center has shown – using the mouse as a model system – that this assumption is in fact erroneous.
Although early dendritic cells differ in their characteristics from those of mature mice, they are nevertheless quite capable of triggering effective immune reactions. The new findings suggest ways of boosting the efficacy of vaccines for young children.
With the help of fluorescent tags attached to specific proteins of interest, Schraml and her colleagues traced the origins and biological properties of dendritic cells in newborn and juvenile mice and compared them with those of mature animals.
These studies revealed that dendritic cells are derived from different source populations, depending on the age of the animal considered. Those found in neonatal animals develop from precursor cells produced in the fetal liver.
As the mice get older, these cells are progressively replaced by cells arising from myeloid precursors, a class of white blood cells that originates from the bone marrow.
However, our experiments demonstrate that – in contrast to the conventional view – a particular subtype of dendritic cells named cDC2 cells is able to activate T-cells and express pro-inflammatory cytokines in young animals. In other words, very young mice can indeed trigger immune reactions.”
Barbara Schraml, Professor, Biomedical Center, Ludwig-Maximilians-Universitaet Muenchen (LMU)
Nevertheless, early cDC2 cells differ in some respects from those found in adult mice. For example, they show age-dependent differences in the sets of genes they express. It turns out that these differences reflect the fact that the signaling molecules (‘cytokines’) to which dendritic cells respond to change as the mice get older.
“Among other things, the array of receptors that recognize substances which are specific to pathogens changes with age,” says Schraml. “Another surprise for us was that early dendritic cells activate one specific subtype of T-cells more effectively than others. Interestingly, this subtype has been implicated in the development of inflammatory reactions.”
The results of the study represent a substantial contribution to our understanding of the functions of dendritic cells, and they could have implications for medical immunology. The immune system of newborns differs from that of more mature individuals insofar as immune responses in early life tend to be weaker than those invoked later in life.
“Our data suggest that it might be possible to enhance the efficacy of vaccinations in childhood by, for example, adapting the properties of the immunizing antigen to the specific capabilities of the juvenile dendritic cells,” says Schraml.
Papaioannou, N. E., et al. (2021) Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice. Nature Communications. doi.org/10.1038/s41467-020-20659-2.
Those of us who avoided COVID-19 over the past year may be somewhat surprised to learn there’s a good chance we’ve already been infected by at least one coronavirus.
They’re thought to be behind up to a third of all common colds. And intriguingly, evidence emerged last year that suggested people who were previously exposed to a common cold coronavirus might have some protection against COVID-19.
So could this cross-protection go the other way? Might the COVID-19 vaccines being rolled out now also cause a dip in seasonal coronaviruses?
While it’s too early to tell, it’s possible. But perhaps not in the way you’d think.
How colds may boost COVID-19 immunity
First, it’s worth looking at how vaccines generate an immune response, and how they compare to real infections.
Vaccines use parts of viruses or bacteria to train what’s called our adaptive immune system.
This part of our immune system protects us against specific microbes. It primarily involves molecules, called antibodies, that neutralise an invading pathogen.
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In the case of COVID-19 vaccines, antibodies are made against the virus’s spike protein, which the virus uses to worm its way into our cells.
Your body needs quite a lot of energy to manufacture antibodies, so — ideally — vaccines also establish a few pathogen-specific immune cells called memory T cells and B cells that hang around long after the initial burst of antibodies has waned.
If a pathogen shows up again, T and B cells spring into action, once again churning out antibodies and eliminating infected cells.
When it comes to contracting an actual coronavirus infection, your body produces an immune response to many parts of the virus — not just its spike proteins.
For instance, they might also produce antibodies against other proteins embedded in the coronavirus’s fatty protective layer.
This means that if another coronavirus — perhaps SARS-CoV-2 — shares these proteins, you might have some level of immunity against it as well.
Might COVID vaccines protect against other coronaviruses?
If they do, it’s unlikely that antibodies generated by jabs will play a role, says Kirsty Short, a virologist at the University of Queensland.
A non-COVID coronavirus would need spike proteins to be incredibly similar to those on SARS-CoV-2 for antibodies to recognise and destroy them.
Antibodies latch onto viruses like a lock and key. If the virus protein key is the wrong size or shape for the antibody lock, nothing happens.
But there is a chance that T cell immunity might step up against other coronaviruses. That’s because for them, the shape of a viral protein isn’t quite as important. They recognise smaller bits of viral proteins in the form of short chains of amino acids, or linear peptides.
“Some of those peptides are shared between seasonal coronaviruses and SARS-CoV-2,” Dr Short says.
And while measuring antibody levels from a blood test is relatively straightforward, it’s not as easy to find out what T cells get up to after a COVID-19 jab.
“In terms of T cell responses, they become a little bit more complex,” Dr Short says.
“The type of peptides that my T cells present to the immune system are going to be different to the type of peptides that your T cells will present.
“That just relates to individual genetic differences.”
Shoring up our first line of defence
There is another way vaccines can boost our immune response against other diseases.
The adaptive immune system is just one part of our immune system. We also have our innate immune system.
It’s our first line of immune defence and responds faster than the adaptive immune system, but it doesn’t target specific pathogens. It goes for all of them.
So if you scrape your knee, your innate immune system quickly produces molecules and recruits and activates immune cells to the area to destroy any bacteria or viruses in the wound.
And for a long time, researchers thought immune system memory, involving B and T cells, was solely part of the adaptive immune system.
But in recent years, scientists have found our innate immune system also has an element of memory.
This is called “trained immunity“, and some vaccines trigger this memory response, Dr Short says.
“Mostly, it’s live vaccines that seem to do it, like the MMR vaccine and live polio vaccine.”
It’s a concept being explored by Nigel Curtis, paediatric infectious diseases physician and scientist at the Murdoch Children’s Research Institute.
He and his team are running an international clinical trial to determine if the tuberculosis vaccine — called Bacillus Calmette-Guérin or BCG — can help protect against severe COVID-19 in healthcare workers.
The BCG vaccine contains live but weakened bacteria that stimulate the immune system, but without causing disease.
And it’s only in the past decade that immunologists have unpicked some of the mechanisms behind it.
Very simply, the BCG vaccine induces metabolic changes in some of the cells involved in the innate immune system, and this affects how they express certain genes.
Overall, it means your innate immune response better deals with any subsequent infections, Professor Curtis says.
“The idea is that you have BCG, and you induce these changes, then when you get infected with SARS-CoV-2, your response to that virus or any virus — because it’s completely agnostic to pathogen — is stronger than it would be in someone who hadn’t previously had BCG.”
Because it’s a general enhancement, it’s not technically cross-protection, and the BCG vaccine should not considered a replacement for COVID-19 vaccines, he adds.
Instead, it’s something that may stop you from becoming severely ill, should you be infected.
The goal of the work is to pinpoint the specific compounds that induce trained immunity.
“What we want to do is find out exactly what those key components are and, once we do that, we can make something that’s perhaps better than BCG — something you’d give to everybody to induce a better immune response early or even later on in life,” Professor Curtis says.
Cross-protection and HPV
One vaccine that granted some cross-protection was the human papillomavirus or HPV jab.
Of the more-than-200 HPV strains, around 40 are sexually transmitted. Two of those strains, 16 and 18, cause more than 70 per cent of cervical cancers worldwide.
Australia kicked off its HPV vaccination program in 2007 with the Gardasil vaccine, which vaccinated against types 16 and 18, as well as 6 and 11 — strains that don’t cause cancer, but are responsible for around 90 per cent of genital warts.
Suzanne Garland, a clinical microbiologist, sexual health physician and director of the Women’s Centre for Infectious Diseases in Melbourne, led a team that assessed HPV prevalence in Australian women eight years after the rollout started.
As well as finding Gardasil prevented HPV 16 and 18 infection, they also found vaccinated women were far less likely to be infected by a further three cancer-causing HPV strains when compared to unvaccinated counterparts.
Those additional strains were genetically similar to those targeted by the vaccine. Types 31 and 33 were much like 16, while 45 was close to 18.
Professor Garland calls this cross-protection a “bonus”, but why it happened in some women and not others isn’t clear.
The latest generation HPV vaccine, Gardasil 9, covers nine high-risk strains — including 16, 18, 31, 33 and 45 — which are responsible for 93 per cent of cervical cancers.
It was only introduced to the National Immunisation Program in 2018, “so it’s important that women who were vaccinated as schoolgirls have regular cervical screenings, because … you’re still at risk of infection and disease for the types not covered by the vaccine”, Professor Garland says.
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Since the virus first emerged in late-2019, over 95.55 million cases and more than 2 million deaths have been reported.
Many countries have commenced targeted vaccination efforts to control the spread of the virus and immunize vulnerable groups. However, vaccine rollout may still lag behind ongoing infections, as fast-spreading new variants threaten many countries. Finding an effective therapy to help patients fight the infection remains crucial.
Passive immunotherapy treatment, wherein SARS-CoV-2-neutralizing antibodies (nAbs) from the plasma of recovered patients are administered to acutely sick patients, is a promising method for COVID-19 treatment in severe cases.
A team of researchers at the University of Washington, Fred Hutchinson Cancer Research Center, and the National Institute of Health, USA, recently studied the neutralizing antibodies from patients recovering from COVID-19 to investigate which clinical factors predict good passive immunotherapy donors.
In the study, published in the Journal of Clinical Investigation, the research team measured SARS-CoV-2-nAb titers in the plasma of 250 people with SARS-CoV-2 infection.
In the USA, convalescent plasma therapy for COVID-19 patients was approved under emergency use authorization by the Food and Drug Administration (FDA) on August 23, 2020. This mode of therapy uses antibody-containing blood from recovered individuals to help promote passive immunity in severely ill patients still battling the infection.
Blood donated by people who have recovered from COVID-19 is processed to remove blood cells, leaving behind the plasma and neutralizing antibodies against SARS-CoV-2.
The plasma given to severely ill patients will help boost the body’s immune system. In a recent phase II clinical trial in Argentina, scientists found that convalescent plasma with high levels of neutralizing antibodies, particularly when given early in the infection, had a marked beneficial health impact.
Yet, not all SARS-CoV-2-infected people produce a strong neutralizing antibody response. Hence, convalescent plasma from donors should be screened for SARS-CoV-2-neutralizing antibody activity to make sure the recovered patients are suitable donors.
In the current study, the researchers tested the serum of 250 potential convalescent plasma donors with confirmed SARS-CoV-2 infection for the presence of SARS-CoV-2 spike protein S1 domain, nucleoprotein (NP), and for neutralizing antibodies.
The team found that among the participants, 97 percent were seropositive on one or more assays. About 60 percent of the donors had nAb titers. The correlates of higher nAb titer included old age, male, and severity of the illness. Also, patients with more severe COVID-19 symptoms, like the difficulty of breathing and fever, had higher levels of neutralizing antibodies against SARS-CoV-2.
Moreover, a longer period between the infection and antibody screening had decreased nAb titers. The study results showed that severe COVID-19 illness produces higher levels of antibodies than less severe illness. This also means that the neutralizing antibodies in the blood of recovered patients wane over time.
COVID-19 seems to be one of a group of infections where the sicker one is, and presumably the more virus and therefore the more antigen that is around, the higher the levels of antibody,” Dr. David Koelle of the Koelle Laboratory, University of Washington, said in a statement.
He explained that the potential cause of this discrepancy is that the immune system in people who had a severe illness, was not effective in stopping it. There is a probable temporal race between the proliferation of the virus and host adaptive immunity.
The researchers concluded that nAb titers correlated with disease severity, sex, and age. Also, they suggested that commercially available SARS-CoV-2 immunoglobulin G (IgG) results can become an alternative for nAb testing.
Functional nAb levels were found to decline and a small proportion of persons recovered from COVID-19 lack adaptive immune responses,” they added.
While the Centers for Disease Control and Prevention say that the number of cases for the 2020-21 flu season is way down this year, it’s still important to keep your immune system strong.
“Now is the time to become a health advocate and shore up your immune system, the body’s natural defense system to ward off illness and reduce your risk of disease,” Dr. Ellen Kamhi, Ph.D., author of “The Natural Medicine Chest,” tells Newsmax. “The efficient functioning of the immune system is of paramount importance to everyone, adults and children alike, since it controls our ability to fend off illness, whether it be a serious threat or even common sniffles.”
“The pigments that give fruits and vegetables their bright colors represent a variety of protective compounds. Eating plant-based foods plays an important role in reducing the risk of breast, prostate and other forms of cancer,” she says.
Here are 10 top immune boosting foods:
Blueberries. The anthocyanins in blueberries destroy free radicals, reduce inflammation, and boost brain health, says Levin. One cup of blueberries provides 15% of the daily recommended amount of vitamin C. Not only is vitamin C a key nutrient that helps the immune system work properly, it is also an antioxidant that helps protect cells from damage.
Sweet potatoes. The beta-carotene in sweet potatoes fights cancer and supports the immune system. They also contain more than three times the recommended amount of vitamin A and are a good source of B6.
Garlic and onions. The allyl sulfides in these vegetables help destroy cancer cells and reduce cell division, notes Levin. Garlic contains the enzyme alliinase, which converts to alliin to allicin that boost immune function. You can also reap the benefits by using aged garlic extract if you do not like the strong taste of the raw or cooked product.
Broccoli. This super healthy veggie and its cousin, Brussel sprouts, contain indoles and lutein which support eye health. They also eliminate excess estrogen and carcinogens from the body.
Tomatoes. Tomatoes are an immune boosting powerhouse. They contain lycopene which helps prevent breast and prostate cancer, says Levin. According to research, lycopene may also reduce your risk of heart disease. Tomatoes also contain potassium which helps control blood pressure and vitamin K which is important for blood coagulation and bone health.
Oil fish. Fish like salmon, trout, anchovies, and sardines are rich in essential omega-3 fatty acids which are a precursor to many compounds that play a defensive role in immune response, says Michelle Dudash, RDN, author of Clean Eating for Busy Families.
Red bell peppers. Keri Glassman, MS., RD., and founder of Nutritious Life, says she hasn’t had a cold in over a decade thanks to the power of peppers. “Red peppers are one of my favorite foods to incorporate into my diet for immune-boosting benefits,” she says. They are particularly rich in vitamin C which is important for immunity, reducing the length and severity of colds, and collagen which keeps your skin healthy.
Black Elderberries. Kamhi, aka The Natural Nurse, says that this delicious fruit, which is readily available in health food stores as a syrup, is a superhero of immune boosters. “It offers gentle yet powerful support for the immune system,” she says. As a plus, the syrup is tasty and has a flavor even kids will love.
Yogurt. Yogurt supports a health digestive system which in turn bolsters the immune system. “The immune system is the main link between our gut bacteria and how it influences our health,” says Gabrielle Geerts, RD, from Boulder, Colorado.
Oil of oregano. Kamhi says the oil is rich in vitamins and minerals that offer beneficial support to the immune system. Oregano is also a natural antioxidant, anti-fungal and antibacterial—which is exactly what your body needs to stay healthy. By consuming oregano in concentrated oil form, you reap the most benefits. If you don’t like the taste of the drops, you can purchase supplements in capsule form.
Dr. Jacob Teitelbaum, M.D., and author of FromFatigued to Fantastic!emphasizes what an important role food plays in our immune health. “Diet is critical to optimal immunity,” he says. “Especially increasing foods that contain zinc, vitamin C, and vitamin D can be beneficial to the immune system.”
When you choose foods that are higher in vitamins and minerals, you’re getting more antioxidants and healthy compounds into your body, and that helps you fight off potential illness, or at least lessen the severity. Take zinc, for instance; one of the best-known immunity boosters that can be found in OTC medicines like Zicam (for alleviating cold symptoms). “Without adequate levels of zinc, the key hormone regulating immunity, called thymulin, simply does not work,” says Teitelbaum. Zinc is usually found in high-protein foods like oysters, chicken and beef.
“By eating a diet higher in fruits and vegetables, increasing exercise, and maintaining a healthy weight, you can improve the overall function of your body, including your immune system,” says Sandy Younan Brikho, MDA, RDN, a registered dietitian nutritionist and weight loss expert. “Research shows that consuming foods that are anti-inflammatory, containing antioxidants, and protein-rich could aid in improving immune function over time.”
Here, we’ve included a list of 15 foods that boost the immune system so you can incorporate them into your diet on your quest for better health.
Almonds are rich in vitamin E, another powerful immune booster. And it doesn’t take more than a small handful of almonds to get your recommended daily amount.
The rich orange color of sweet potatoes indicates that sweet potatoes are high in beta carotene, which can increase your body’s production of white blood cells, says Olivia Audrey, ND, board-certified doctor of natural medicine.
For a healthy and protective dose of zinc on the go, grab a handful of pumpkin seeds and enjoy a simple—and immune boosting—snack.
Used for centuries as a natural remedy for diseases of all types, garlic is a must-add to your diet during cold and flu season. One study found that use of a garlic supplement dramatically reduced the prevalence of colds among participants.
This versatile fruit is packed with antioxidants. You can use the seeds in a salad, or simply drink the juice for a similar effect.
Elderberries are a favorite immune-boosting food, since they contain antioxidants that may help reduce inflammation, says Brikho.
Similar to elderberries and cranberries, acai berries are high in antioxidants and will keep your immune system in top condition.
Protein-rich foods like beef, poultry, and eggs can help with T-cell function that kills infected host cells, says Brikho.
Made by simmering the bones and connective tissues of animals, bone broth is basically the gold standard of health-inducing foods. Among a host of other benefits, it’s said to increase immunity as well.
Every winter, people look for ways to protect themselves against colds, the flu, and other infections — and with a pandemic happening, having a strong immune system is even more important. This is especially true if you’re living with diabetes. Diabetes can affect your immune response, making you more susceptible to infections. There are several lifestyle habits that can help — things like consistent exercise, getting enough sleep, and minimizing stress. Controlling your blood sugar is also paramount in maintaining a strong immune response.
Looking for ways to boost your immune system? Consider adding in one of these eight immune-boosting foods to your daily meals.
Many people turn to vitamin C when they feel a cold coming on because it is known for promoting the production of white blood cells, which are necessary in fighting off infections. Fruits like grapefruit, oranges, tangerines, lemons, and limes are wonderful sources of this powerhouse nutrient. Avoid citrus juices, which can raise your blood sugar. Opt for whole pieces of fruit instead to get the added benefits of fiber that aids in blood sugar regulation.
Many fermented foods, like yogurt, kimchi, miso, tempeh, kombucha, and sauerkraut, contain high levels of live, active cultures, which are the “good” bacteria that help protect the body from infection. In fact, these microorganisms are responsible for more than 75% of the immune system! Aim to eat a variety of probiotic-rich foods every day to enhance microbial diversity in your gut. Having an array of healthy gut microbes promotes optimal digestion and can boost immune response.
Nuts and Seeds
Vitamin E is another critical nutrient that helps to maintain immune system function. Nuts and seeds, such as almonds, hazelnuts, Brazil nuts, and sunflower seeds, are excellent sources of the vitamin. Nuts and seeds also contain healthy fats, protein, and fiber, which help regulate blood sugar.
Grandma’s favorite cold remedy may have some healing powers after all! Chicken is high in vitamin B6, which is essential in making antibodies and other chemical reactions in the body that improve immune response. Homemade stock or broth made by boiling chicken bones also contains nutrients that promote gut health and a healthy immune system.
Hot tea is known for soothing a sore throat when you are sick, but it can also contain a ton of immune-boosting nutrients. Green, black, and white tea varieties all contain flavonoids that are powerful antioxidants that fight off free radicals in the body. Fresh ginger tea is another great option, as ginger is known to decrease inflammation and reduce blood sugars.
Onions and Garlic
Onions and garlic are not only good for making meals more flavorful, they are also loaded with antioxidants that fight viruses and bacteria. Garlic also contains unique sulfuric compounds that support the body’s natural detoxification systems.
Beans and other legumes, like peas and lentils, have many nutritional benefits for those living with diabetes. They contain high amounts of fiber, which provide a sustained source of energy without a spike in blood sugar.
Beans are also a great source of zinc, which is an essential mineral that needs to be eaten regularly since the human body does not store it. Zinc affects many aspects of the immune system and has also been shown to improve glycemic control in those living with diabetes.
Bell peppers are another excellent source of vitamin C and help eliminate free radicals from the body. Just 1 cup of sliced red bell pepper contains 130% of the recommended daily value of vitamin C. And because bell peppers are a non-starchy vegetable, they have minimal impact on blood glucose levels, making them an excellent snack choice or addition to daily meals like scrambled eggs or a green salad.
An unfortunate truth about the use of mechanical ventilation to save the lives of patients in respiratory distress is that the pressure used to inflate the lungs is likely to cause further lung damage.
In a new study, scientists identified a molecule that is produced by immune cells during mechanical ventilation to try to decrease inflammation, but isn’t able to completely prevent ventilator-induced injury to the lungs.
The team is working on exploiting that natural process in pursuit of a therapy that could lower the chances for lung damage in patients on ventilators. Delivering high levels of the helpful molecule with a nanoparticle was effective at fending off ventilator-related lung damage in mice on mechanical ventilation.
Our data suggest that the lungs know they’re not supposed to be overinflated in this way, and the immune system does its best to try to fix it, but unfortunately it’s not enough. How can we exploit this response and take what nature has done and augment that? That led to the therapeutic aims in this study.”
Dr. Joshua A. Englert, Study Co-lead Author, Assistant Professor, Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Wexner Medical Center
The work builds upon findings from the lab of co-lead author Samir Ghadiali, professor and chair of biomedical engineering at Ohio State, who for years has studied how the physical force generated during mechanical ventilation activates inflammatory signaling and causes lung injury.
Efforts in other labs to engineer ventilation systems that could reduce harm to the lungs haven’t panned out, Ghadiali said.
“We haven’t found ways to ventilate patients in a clinical setting that completely eliminates the injurious mechanical forces,” he said. “The alternative is to use a drug that reduces the injury and inflammation caused by mechanical stresses.”
The research is published today (Jan. 12, 2021) in Nature Communications.
Though a therapy for humans is years away, the progress comes at a time when more patients than ever before are requiring mechanical ventilation: Cases of acute respiratory distress syndrome (ARDS) have skyrocketed because of the ongoing COVID-19 pandemic. ARDS is one of the most frequent causes of respiratory failure that leads to putting patients on a ventilator.
“Before COVID, there were several hundred thousand cases of ARDS in the United States each year, most of which required mechanical ventilation. But in the past year there have been 21 million COVID-19 patients at risk,” said Englert, a physician who treats ICU patients.
The immune response to ventilation and the inflammation that comes with it can add to fluid build-up and low oxygen levels in the lungs of patients already so sick that they require life support.
The molecule that lessens inflammation in response to mechanical ventilation is called microRNA-146a (miR-146a). MicroRNAs are small segments of RNA that inhibit genes’ protein-building functions – in this case, turning off the production of proteins that promote inflammation.
The researchers found that immune cells in the lungs called alveolar macrophages – whose job is to protect the lungs from infection – activate miR-146a when they’re exposed to pressure that mimics mechanical ventilation. This action makes miR-146a part of the innate, or immediate, immune response launched by the body to begin its fight against what it is perceiving as an infection – the mechanical ventilation.
“This means an innate regulator of the immune system is activated by mechanical stress. That makes me think it’s there for a reason,” Ghadiali said. That reason, he said, is to help calm the inflammatory nature of the very immune response that is producing the microRNA.
The research team confirmed the moderate increase of miR-146a levels in alveolar macrophages in a series of tests on cells from donor lungs that were exposed to mechanical pressure and in mice on miniature ventilators. The lungs of genetically modified mice that lacked the microRNA were more heavily damaged by ventilation than lungs in normal mice – pointing to miR-146a’s protective role in lungs during mechanical breathing assistance. Finally, the researchers examined cells from lung fluid of ICU patients on ventilators and found miR-146a levels in their immune cells were increased as well.
The problem: The expression of miR-146a under normal circumstances isn’t high enough to stop lung damage from prolonged ventilation.
The intended therapy would be introducing much higher levels of miR-146a directly to the lungs to ward off inflammation that can lead to injury. When overexpression of miR-146a was prompted in cells that were then exposed to mechanical stress, inflammation was reduced.
To test the treatment in mice on ventilators, the team delivered nanoparticles containing miR-146a directly to mouse lungs – which resulted in a 10,000-fold increase in the molecule that reduced inflammation and kept oxygen levels normal. In the lungs of ventilated mice that received “placebo” nanoparticles, the increase in miR-146a was modest and offered little protection.
From here, the team is testing the effects of manipulating miR-146a levels in other cell types – these functions can differ dramatically, depending on each cell type’s job.
“In my mind, the next step is demonstrating how to use this technology as a precision tool to target the cells that need it the most,” Ghadiali said.
Bobba, C.M., et al. (2021) Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates injury during mechanical ventilation. Nature Communications. doi.org/10.1038/s41467-020-20449-w.
With the Proof of Concept funding line, the ERC grants recipients of ERC frontier research funds (Starting, Consolidator, Advanced or Synergy grants) with 150.000 Euro to develop promising ideas with commercial or societal potential to the proof of concept stage. With this funding, Olaf Groß and his team in the Metabolism and Inflammation Group at the Institute of Neuropathology of the Medical Center – University of Freiburg will test whether a new class of immune activating drugs they discovered can boost the effectiveness of cancer immunotherapies or vaccines against infectious diseases.
Groß studies a protein complex called the inflammasome within macrophages, specialized cells of the body’s defense system that patrol tissues for signs of danger. When their inflammasome is activated, macrophages sound the alarm by releasing of potent factors called cytokines. These cytokines alert other cells in the body, initiating an inflammatory response that helps other immune cells attack cancer cells or infections, explains Groß. Within the context of his ERC Starting Grant, he and his team discovered a new class of small molecules that potently and specifically activate the inflammasome, acting like turbo boosters for the immune system.
“There has been great excitement surrounding the development of inflammasome inhibitors for the treatment of inflammatory diseases”, Groß explains. “But we think that in the right clinical setting inflammasome activators might be just as valuable”, he adds. During the proof of concept phase, Groß and his team will test whether his IMMUNOSTIM compounds improve the efficacy of cancer treatment and vaccines.
We will also be looking for commercial partners for further development of this promising new class of immunotherapeutics.”
Olaf Groß, University of Freiburg
Groß received his doctorate at Technical University of Munich in 2008. Following postdoctoral research at the University of Lausanne in Switzerland he established an independent research group focused on the inflammasome at Klinikum rechts der Isar in Munich. Since 2017, Groß is Professor at the University of Freiburg in the Institute of Neuropathology of the University Medical Center. He is a Speaker of the University of Freiburg’s Emerging Field in Metabolism Research and member of the Cluster of Excellence CIBSS – the Centre for Integrative Biological Signalling Studies. Within CIBSS he studies the signaling mechanisms responsible for inflammasome activation by the IMMUNOSTIM compounds and screens for new molecules that modulate metabolic and immune signaling processes.
UC San Francisco scientists have discovered a new way to control the immune system’s “natural killer” (NK) cells, a finding with implications for novel cell therapies and tissue implants that can evade immune rejection. The findings could also be used to enhance the ability of cancer immunotherapies to detect and destroy lurking tumors.
The study, published January 8, 2021 in the Journal of Experimental Medicine, addresses a major challenge for the field of regenerative medicine, said lead author Tobias Deuse, MD, the Julien I.E. Hoffman, MD, Endowed Chair in Cardiac Surgery in the UCSF Department of Surgery.
“As a cardiac surgeon, I would love to put myself out of business by being able to implant healthy cardiac cells to repair heart disease,” said Deuse, who is interim chair and director of minimally invasive cardiac surgery in the Division of Adult Cardiothoracic Surgery. “And there are tremendous hopes to one day have the ability to implant insulin-producing cells in patients with diabetes or to inject cancer patients with immune cells engineered to seek and destroy tumors. The major obstacle is how to do this in a way that avoids immediate rejection by the immune system.”
Deuse and Sonja Schrepfer, MD, PhD, also a professor in the Department of Surgery’s Transplant and Stem Cell Immunobiology Laboratory, study the immunobiology of stem cells. They are world leaders in a growing scientific subfield working to produce “hypoimmune” lab-grown cells and tissues — capable of evading detection and rejection by the immune system. One of the key methods for doing this is to engineer cells with molecular passcodes that activate immune cell “off switches” called immune checkpoints, which normally help prevent the immune system from attacking the body’s own cells and modulate the intensity of immune responses to avoid excess collateral damage.
Schrepfer and Deuse recently used gene modification tools to engineer hypoimmune stem cells in the lab that are effectively invisible to the immune system. Notably, as well as avoiding the body’s learned or “adaptive” immune responses, these cells could also evade the body’s automatic “innate” immune response against potential pathogens.
To achieve this, the researchers adapted a strategy used by cancer cells to keep innate immune cells at bay: They engineered their cells to express significant levels of a protein called CD47, which shuts down certain innate immune cells by avtivating a molecular switch found on these cells, called SIRPα. Their success became part of the founding technology of Sana Biotechnology, Inc, a company co-founded by Schrepfer, who now directs a team developing a platform based on these hypoimmune cells for clinical use.
But the researchers were left with a mystery on their hands — the technique was more successful than predicted. In particular, the field was puzzled that such engineered hypoimmune cells were able to deftly evade detection by NK cells, a type of innate immune cell that isn’t supposed to express a SIRPα checkpoint at all.
NK cells are a type of white blood cell that acts as an immunological first responder, quickly detecting and destroying any cells without proper molecular ID proving they are “self” — native body cells or at least permanent residents — which takes the form of highly individualized molecules called MHC class I (MHC-I).
When MHC-I is artificially knocked out to prevent transplant rejection, the cells become susceptible to accelerated NK cell killing, an immunological rejection that no one in the field had yet succeeded in inhibiting fully. Deuse and Schrepfer’s 2019 data, published in Nature Biotechnology, suggested they might have stumbled upon an off switch that could be used for that purpose.
All the literature said that NK cells don’t have this checkpoint, but when we looked at cells from human patients in the lab we found SIRPα there, clear as day. We can clearly demonstrate that stem cells we engineer to overexpress CD47 are able to shut down NK cells through this pathway.”
Sonja Schrepfer, MD, PhD, Professor, Department of Surgery’s Transplant and Stem Cell Immunobiology Laboratory
To explore their data, Deuse and Schrepfer approached Lewis Lanier, PhD, a world expert in NK cell biology. At first Lanier was sure there must be some mistake, because several groups had looked for SIRPα in NK cells already and it wasn’t there. But Schrepfer was confident in her team’s data.
“Finally it hit me,” Schrepfer said. “Most studies looking for checkpoints in NK cells were done in immortalized lab-grown cell lines, but we were studying primary cells directly from human patients. I knew that must be the difference.”
Further examination revealed that NK cells only begin to express SIRPα after they are activated by certain immune signaling molecules called cytokines. As a result, the researchers realized, this inducible immune checkpoint comes into effect only in already inflammatory environments and likely functions to modulate the intensity of NK cells’ attack on cells without proper MHC class I identification.
“NK cells have been a major barrier to the field’s growing interest in developing universal cell therapy products that can be transplanted “off the shelf” without rejection, so these results are extremely promising,” said Lanier, chair and J. Michael Bishop Distinguished Professor in the Department of Microbiology and Immunology.
In collaboration with Lanier, Deuse and Schrepfer comprehensively documented how CD47-expressing cells can silence NK cells via SIRPα. While other approaches can silence some NK cells, this was the first time anyone has been able to inhibit them completely. Notably, the team found that NK cells’ sensitivity to inhibition by CD47 is highly species-specific, in line with its function in distinguishing “self” from potentially dangerous “other”.
As a demonstration of this principle, the team engineered adult human stem cells with the rhesus macaque version of CD47, then implanted them into rhesus monkeys, where they successfully activated SIRPα in the monkeys’ NK cells, and avoided killing the transplanted human cells. In the future the same procedure could be performed in reverse, expressing human CD47 in pig cardiac cells, for instance, to prevent them from activating NK cells when transplanted into human patients.
“Currently engineered CAR T cell therapies for cancer and fledgling forms of regenerative medicine all rely on being able to extract cells from the patient, modify them in the lab, and then put them back in the patient. This avoids rejection of foreign cells, but is extremely laborious and expensive,” Schrepfer said. “Our goal in establishing a hypoimmune cell platform is to create off-the shelf products that can be used to treat disease in all patients everywhere.”
The findings could also have implications for cancer immunotherapy, as a way of boosting existing therapies that attempt to overcoming the immune checkpoints cancers use to evade immune detection. “Many tumors have low levels of self-identifying MHC-I protein and some compensate by overexpressing CD47 to keep immune cells at bay,” said Lanier, who is director of the Parker Institute for Cancer Immunotherapy at the UCSF Helen Diller Family Comprehensive Cancer Center. “This might be the sweet spot for antibody therapies that target CD47.”