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LEXINGTON, Ky. (LEX 18) With COVID-19, flu season and winter weather starting to arrive, there are a lot of things right now that affect ones health. Having a strong, balanced immune system can help people stay healthy.

So that they're much less likely to get an infection or if they happen to get sick, they might have an easier time or an easier recovery, said Dr. Madeline Fisher with CHI Saint Joseph Health.

Overall, it's important to know the immune system is just that - a system, so there is no one magic trick to strengthening it. It comes down to a balance of healthy habits.

Dr. Fishers first tip is to maintain a healthy diet of whole foods, including fruits and vegetables. Vitamin supplements can help, but its better to get nutrients from a natural source.

Also making sure to drink enough water, so that your body is able to flush out any toxins that would be in your system, said Dr. Fisher.

Some people with certain health concerns may need supplements. Dr. Fisher says if thats the case, its important to consult with a doctor first.

Exercise is also important, but that can be difficult to keep up with during winter weather and gym restrictions. Dr. Fisher says even a short brisk walk every day or every couple of days can help.

Also, take advantage of colder temperatures to grab a blanket and head to bed a little earlier.

Making sure to get enough sleep so that you're well-rested so your immune system is able to fight off infections, said Dr. Fisher. The amount of sleep that someone needs can vary depending on the person, but most adults need eight or nine hours a night.

Other tips include minimizing stress, practicing frequent handwashing, and keeping up with regular doctor visits.

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How to keep your immune system strong this winter - LEX18 Lexington KY News

The new coronavirus vaccine appears to be extremely effective - blocking serious illness entirely in randomized trials - and it has passed strict safety reviews and won emergency authorization from regulators in five countries so far, including the United States. But news bulletins in the past week provided a reminder that this remains a revolutionary pharmaceutical agent that will be scrutinized in the months ahead as shots go into arms.

Among the unknowns: To what extent does the vaccine prevent infection vs. simply preventing clinical illness?

Can a vaccinated person who becomes infected, but not sick, transmit the virus to someone else? Thats a pivotal factor in forecasting how rapidly the pandemic will be quashed once there is widespread distribution of vaccines.

Another unknown: How long will the protective effect of the vaccine last?

Scientists will also be vigilant for severe allergic reactions. Last week, two health-care workers in the United Kingdom who were among the first batch of people to get the vaccine after it was authorized developed anaphylaxis, a severe allergic response.

Both were known to have a history of severe allergic reactions, and both were treated and recovered. A third person reportedly suffered a rapid heartbeat. British authorities issued new guidance saying people with a history of anaphylaxis should consult with their doctor before taking the vaccine. Researchers do not know what substance in the vaccine formula triggered the severe allergic response.

When you make a decision to launch a vaccine like this, its not because you know everything, said Paul Offit, a pediatrician and vaccine expert at Childrens Hospital of Philadelphia and member of a Food and Drug Administration advisory panel that endorsed the vaccine Thursday. But he added, I think we know enough.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Saturday, I dont think that the allergic reactions are even close to being a show-stopper for the Pfizer vaccine.

He said the criteria for participation in the random trials excluded people with a history of severe allergic reactions, and it is not surprising that, as the vaccine reached the general population, such rare allergic responses emerged. He said officials will continue to monitor the safety of the vaccines long after they have received emergency authorization.

Observation of safety does not end when you start administering vaccines to the general public, he said.

The big picture is that covid-19, the illness caused by the coronavirus, is a known killer, and has already taken nearly 300,000 lives in the United States and more than 1 million worldwide. Vaccines are essential to crushing the pandemic. U.S. public health officials hope at least 70 percent of the population will agree to be inoculated with one of the vaccines rolled out in the coming months.

I feel like were doing something historic, and theres multiple vaccines, and we should be able to lick this, said immunologist Stanley Perlman of the University of Iowa, who is also a member of the advisory panel that voted Thursday to bless the Pfizer-BioNTech vaccine.

But he acknowledged he is concerned about potential side effects that may not yet have been identified.

I worry about something coming up that we dont know anything about. The unknown, he said.

Two criteria for a good vaccine are effective and safe. The coronavirus vaccine technically named BNT162b2 and developed by industry giant Pfizer and BioNTech meets both standards, according to the professionals who have developed the vaccine, conducted randomized clinical trials and reviewed resulting data during the past several months.

It has received emergency authorization from the FDA and from regulators in the United Kingdom, Canada, Bahrain and Saudi Arabia. Another, similar vaccine frombiotechnology companyModerna is poised to be greenlighted by the FDA this week after a meeting of an advisory panel.

Data from the randomized Pfizer-BioNTech trial showed the two-dose vaccine to be 100 percent effective in preventing severe illness from covid-19.

But in roughly half the people who get the shot, it can produce modest side effects, including fever, headache, fatigue and pain at the injection site. Thats typical for most vaccines.

This is not a flaw or a failure, vaccine experts hasten to point out. Side effects are a sign the immune system is kicking into gear, as intended. Theyre a feature and not a bug, to borrow the language of computer programmers.

Things like fever or soreness at the injection site are normal, and actually they indicate that your body is reacting to the vaccine, which is what you want, said Ellen F. Foxman, an immunologist at the Yale School of Medicine. Thats a good thing.

Side effects were roughly the same in trial volunteers who got the vaccine and those who got a saltwater placebo.

The immune system needs a better public-relations team, because its just the immune system doing what it does, Offit said.

The newly authorized vaccine, like the Moderna shot, uses a synthesized scrap of genetic information, called messenger RNA, that is wrapped in a protective fat layer to keep it from disintegrating. When it goes into cells in the muscle of the upper arm, it incites cellular machinery to manufacture a protein that mimics the shape of the spike protein that protrudes from the surface of the coronavirus.

At no point, in this type of vaccine, is the coronavirus itself or even part of the coronavirus injected into the body. The body, in effect, becomes the vaccine maker, creating a new protein that triggers an immune response. The immune system manufactures antibodies that can disable anything with structural features resembling this protein - including the coronavirus.

Such a vaccine has never been deployed before.

Its very important to think about the whole picture, Foxman said. The vaccine prevents a disease that we know has a lot of bad outcomes, right? Mortality is an outcome - death.

She added, To me its very clear its very beneficial to avoid all the known problems of getting covid 19. I would take this vaccine in a minute if I were offered it.

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Coronavirus vaccines can have side effects - that typically means they're working - Anchorage Daily News

Male and female Schistosomes.

Credit: Alaa. Source: creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Couple_of_Schistosoma_mansoni.jpg

Schistosomes are a group of parasitic flatworms responsible for causing the neglected tropical diseases of intestinal and urinary schistosomiasis. According to the World Health Organisation, human schistosomiasis is prevalent across 78 countries, in both tropical and sub-tropical regions, and is estimated to affect over 200 million people globally. Schistosomiasis is also considered by the W.H.O. to rank second only to malaria among parasitic diseases in terms of prevalence and socioeconomic burden in an infected community.

The enormous public health and economic burden results in infected individuals and their families being stuck in a cycle of poverty; where they are unable to improve their health due to financial constraints, but also struggle to maintain economic productivity because of their poor health.

In large part, these health, economic and social consequences of schistosome infection are caused by chronic, long-term infections. Without treatment, these parasitic worms have been shown to be able to persist inside a human host for over a decade (here is a case where they had been present for over 38 years!), but how can they survive inside a hosts blood vessels for so many years?

Schistosome physiology enables long-term infection

Schistosomes have a hugely complex life cycle, with an intermediate snail host and a definitive mammalian host.

Upon mammalian host invasion, schistosomes transform through multiple body plans (Cercariae, Schistosomula and Adult), where they eventually reside in their mammalian hosts vasculature, pair with an individual of the opposite sex, and produce thousands of eggs.

However, this is not a happily ever after for our pair of parasitic worms. The hosts vasculature is an extremely hostile environment, brimming with a range of immune components and molecules, tirelessly trying to recognise, bind and kill the parasites. To survive for such a long time inside a human host, schistosomes have (had to) become master manipulators of their environment and display evolutionarily refined characteristics to ensure their long-term survival.

It is well documented that the Schistosome outer surface layers (the tegument) are crucially important in facilitating host immune evasion and maintaining long-term intravascular infection, as this area is highly accessible to immune molecules. However, the parasites digestive tract has now been found to be equally as valuable in helping the parasite to evade the hosts immune system.

The oesophageal gland is essential for survival inside the mammalian host

Jayhun Lee and colleagues at the Morgridge Institute for Research and Howard Hughes Medical Institute of UoW- recently published invaluable research into schistosome digestive tract development, potential mechanisms behind prolonged schistosomiasis infection, and methods of host immune system evasion.

The researchers found, much to their surprise, that an accessory organ of the schistosome digestive tract called the oesophageal gland (OG) develops before the rest of the digestive system. As the digestive system hasnt been fully formed, and blood feeding hasnt started yet, it led Jayhun and colleagues to suggest that the OG has a role in schistosome processes beyond just nutrient uptake and host blood digestion.

For example, the OG is known to secrete a diverse assortment of proteins and other molecules, many of which have unknown functions beyond their demonstrated host protein interaction capabilities. One hypothesis (increasingly being shown to be true) is that OG protein secretions can bind, block, and mop up host antibodies and certain other immune cells before they enter the schistosomes blind gut, acting as a barrier to the hosts immune system. This OG secreted protein barrier could prevent immune molecules from causing direct damage to the gut, or indirect damage by further enhancing the immune response.

In one of their experiments to test the role of the OG in parasite survival, FoxA (a Forkhead-box transcription factor), a key regulator in OG development and maintenance was knocked out using RNAi, resulting in the complete absence of a normal functioning OG.

These parasites lacking an OG were rapidly killed by the hosts immune system in normal immunocompetent mice. However, in mice genetically engineered to lack an immune response, the parasites without an OG survived- showing that, without the OG to mediate protection from the hosts immune molecules, white blood cells could gain access to the parasites gut, enabling recognition of parasite gut tissues, and significantly enhancing killing of the parasite from the inside out.

How can we take advantage of these mechanisms?

Identification of OG-secreted proteins (that manipulate the hosts immune system) and analysis of their interactions with host immune molecules could provide novel antigens with great potential as vaccine targets.

One such group of secreted proteins with considerable promise are the Venom Allergen-Like (VAL) proteins, a group found in a variety of other parasitic worms and organisms. Several VAL proteins have been shown to be released from the OG in Schistosoma mansoni, namely VAL-6, VAL-7 and VAL-13 proteins; however, the specific roles and exact functions of these proteins in the immune evasion process still remains largely unknown.

Additionally, the authors suggest that the identification of genes and proteins downstream of FoxA may help us to selectively disrupt the proper function of the OG, promoting and facilitating schistosome killing by the hosts immune system. Also, as the OG develops during schistosome larval stages, any therapeutic targets could be effective against both immature/larval stages and adult worms, something that the current drug of choice, Praziquantel, cannot do.

With future efforts and continued research into the OG and its associated protein secretions it is possible we may discover a highly promising, novel antigen with great promise as a vaccine target something that will be essential to control and eliminate this disease going forward.

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Investigating the importance of the Schistosome digestive tract in host immune evasion, parasite survival and novel vaccine development - BugBitten -...

A new approach for COVID-19 testing that detects a distinct pattern of immune gene expression in infected individuals could be used as a check against possible errors generated by the standard tests that directly detect the SARS-CoV-2 virus.

Researchers from University of California, San Francisco (UCSF; San Francisco, CA, USA) and Chan Zuckerberg Biohub (San Francisco, CA, USA) have developed the new COVID-19 testing approach that measures a patients immune response for better diagnosis. The new testing approach analyzes completely different molecules - from the person infected, rather than from the virus that infects the person although it can be implemented using the same PCR technology on the same nasal swab samples. It could be used as a standalone test, or even combined into the same testing panels used in standard PCR tests to detect the virus. Combining the technologies could lessen the chances of false negative or false positive results, according to the researchers.

The UCSF scientists created three proof-of-concept versions of the new test - one based on readouts of gene activity from three key genes, one based on readouts from 10 genes, and one based on 27 genes. The tests independently detected COVID-19 infection in clinically confirmed cases, increasing in sensitivity with the number of genes included. The researchers aim to use one of these measures of gene activation both to flag false negative viral PCR tests, in which direct viral detection fails, and to rule out false positive results, which may arise from cross-contamination between samples in testing labs.

To determine which changes in gene activity were distinctive to SARS-CoV-2 infection the researchers first surveyed all the genetic material in swab samples from the upper respiratory tract, so that they could identify the most important and predictive indicators. The researchers examined samples from patients with respiratory symptoms who were tested for COVID-19 as a possible explanation of their illness. The tests showed many of the patients did have COVID-19, but some of them turned out to be infected with more common respiratory viruses (like the flu) or to be suffering from nonviral conditions.

With computer algorithms and a great deal of number crunching, the UCSF scientists were able to identify a distinct pattern of gene expression associated with a tamping down of specific immune responses that occurs early during SARS-CoV-2 infection. The changes differed from those seen in other viral respiratory infections or non-viral respiratory illnesses, allowing for a specific diagnosis of COVID-19. The pattern of immunosuppressive gene expression the researchers identified in COVID-19 may explain the stealthy nature of this highly transmissible virus, according to the researchers.

"Without even having to detect the virus itself, these tests to measure changes in the expression of immune-related genes can determine whether or not someone has COVID-19," said co-senior study author Chaz Langelier, MD, PhD, assistant professor in the Division of Infectious Diseases in the UCSF Department of Medicine.

"We have concluded from our work that there is an immunosuppressive effect taking place that prevents symptoms from developing early during infection despite high levels of viral replication. It's a brilliant strategy, if you're a virus," added Langelier. "Our findings of a diminished inflammatory response by the innate immune system suggest that treatments that suppress the immune system early during COVID-19 infection are unlikely to be beneficial."

Related Links:University of California, San Francisco Chan Zuckerberg Biohub

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New COVID-19 Testing Approach That Measures Immune Response Can Be Combined with Standard PCR Tests for Accurate Diagnosis - HospiMedica

We can readily understand why investors are attracted to unprofitable companies. For example, although software-as-a-service business Salesforce.com lost money for years while it grew recurring revenue, if you held shares since 2005, you'd have done very well indeed. But the harsh reality is that very many loss making companies burn through all their cash and go bankrupt.

Given this risk, we thought we'd take a look at whether ISR Immune System Regulation Holding (STO:ISR) shareholders should be worried about its cash burn. In this article, we define cash burn as its annual (negative) free cash flow, which is the amount of money a company spends each year to fund its growth. Let's start with an examination of the business' cash, relative to its cash burn.

Check out our latest analysis for ISR Immune System Regulation Holding

A company's cash runway is the amount of time it would take to burn through its cash reserves at its current cash burn rate. As at June 2020, ISR Immune System Regulation Holding had cash of kr49m and such minimal debt that we can ignore it for the purposes of this analysis. In the last year, its cash burn was kr28m. So it had a cash runway of approximately 21 months from June 2020. That's not too bad, but it's fair to say the end of the cash runway is in sight, unless cash burn reduces drastically. You can see how its cash balance has changed over time in the image below.

ISR Immune System Regulation Holding didn't record any revenue over the last year, indicating that it's an early stage company still developing its business. Nonetheless, we can still examine its cash burn trajectory as part of our assessment of its cash burn situation. Over the last year its cash burn actually increased by 4.9%, which suggests that management are increasing investment in future growth, but not too quickly. However, the company's true cash runway will therefore be shorter than suggested above, if spending continues to increase. ISR Immune System Regulation Holding makes us a little nervous due to its lack of substantial operating revenue. We prefer most of the stocks on this list of stocks that analysts expect to grow.

While its cash burn is only increasing slightly, ISR Immune System Regulation Holding shareholders should still consider the potential need for further cash, down the track. Issuing new shares, or taking on debt, are the most common ways for a listed company to raise more money for its business. One of the main advantages held by publicly listed companies is that they can sell shares to investors to raise cash and fund growth. We can compare a company's cash burn to its market capitalisation to get a sense for how many new shares a company would have to issue to fund one year's operations.

ISR Immune System Regulation Holding's cash burn of kr28m is about 14% of its kr195m market capitalisation. Given that situation, it's fair to say the company wouldn't have much trouble raising more cash for growth, but shareholders would be somewhat diluted.

Even though its increasing cash burn makes us a little nervous, we are compelled to mention that we thought ISR Immune System Regulation Holding's cash runway was relatively promising. While we're the kind of investors who are always a bit concerned about the risks involved with cash burning companies, the metrics we have discussed in this article leave us relatively comfortable about ISR Immune System Regulation Holding's situation. On another note, ISR Immune System Regulation Holding has 4 warning signs (and 2 which make us uncomfortable) we think you should know about.

Of course ISR Immune System Regulation Holding may not be the best stock to buy. So you may wish to see this free collection of companies boasting high return on equity, or this list of stocks that insiders are buying.

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This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. *Interactive Brokers Rated Lowest Cost Broker by StockBrokers.com Annual Online Review 2020

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com.

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We Think ISR Immune System Regulation Holding (STO:ISR) Can Afford To Drive Business Growth - Simply Wall St

CHICO, Calif. -- It's the holiday season, and this Thanksgiving, most people engaged in activities that can lower immunity, like eating a lot of sugar, drinking alcohol in excess, in addition to experiencing increased stress due to the holidays.

Dr. Rand McClain, an expert in restorative and regenerative health and the Chief Medical Officer of LCR Health, shows us how Thanksgiving traditions and habits could be harmful to our immune systems and what we can do to get our immune systems back on track and stay healthy.

Here are a few of his suggestions:

1) Adequate sleep Aim for regular sleep 7 9 hours nightly and during roughly the sameperiod (ex. 11p 7a each night rather than at varying times, especially as occurs with"shift work").

2) Daily exercise Anything is better than nothing but ideally a minimum of 30 minutes, 3times per week of effort that amounts to brisk walking. 5 6 times per week would beeven better, and efforts of an hour each time would be even better. However, morethan that is not necessarily better.

3) Proper nutrition This includes staying hydrated, eating a balanced array of whole, non-processed foods, and spending the time to find what diet works best for you (one dietdoes not fit all). In addition, avoid overeating. Most people eat more than is necessaryfor good immune health. Keep sufficient fiber in the diet to maintain regular bowelmovements and a healthy gut microbiome now considered a major factor inmaintaining healthy immune function.

4) Modulate and avoid excess stress Breathing exercises and other methods (eg,meditation and yoga) of reducing stress (and excess cortisol levels) can help keep theimmune system functioning at its best.

5) Avoid excess alcohol consumption and smoking both known to have negative effectson immune function.

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Recover your immune system through the holidays - Action News Now

In 2021 hundreds of millions of people will be vaccinated against SARS-CoV-2. The success of that COVID-19 vaccination campaign will heavily depend on public trust that the vaccines are not only effective, but also safe. To build that trust, the medical and scientific communities have a responsibility to engage in difficult discussions with the public about the significant fraction of people who will experience temporary side effects from these vaccines.

I am an immunologist who studies the fundamentals of immune responses to vaccination, so part of that responsibility falls on me.

Simply put, receiving these vaccines will likely make a whole lot of people feel crappy for a few days. Thats probably a good thing, and its a far better prospect than long-term illness or death.

In 1989, immunologist Charles Janeway published an article summarizing the state of the field of immunology. Until that point, immunologists had accepted that immune responses were initiated when encountering something foreign bacteria, viruses, and parasites that was non-self.

Janeway suspected that there was more to the story, and famously laid out what he referred to as the immunologists dirty little secret: Your immune system doesnt just respond just to foreign things. It responds to foreign things that it perceives to be dangerous.

Now, 30 years later, immunologists know that your immune system uses a complex set of sensors to understand not only whether or not something is foreign, but also what kind of threat, if any, a microbe might pose. It can tell the difference between viruses like SARS-CoV-2 and parasites, like tapeworms, and activate specialized arms of your immune system to deal with those specific threats accordingly. It can even monitor the level of tissue damage caused by an invader, and ramp up your immune response to match.

Sensing the type of threat posed by a microbe, and the level of intensity of that threat, allows your immune system to select the right set of responses, wield them precisely, and avoid the very real danger of immune overreaction.

Vaccines work by introducing a safe version of a pathogen to a patients immune system. Your immune system remembers its past encounters and responds more efficiently if it sees the same pathogen again. However, it generates memory only if the vaccine packs enough danger signals to kick off a solid immune response.

As a result, your immune systems need to sense danger before responding is at once extremely important (imagine if it started attacking the thousands of species of friendly bacteria in your gut!) and highly problematic. The requirement for danger means that your immune system is programmed not to respond unless a clear threat is identified. It also means that if Im developing a vaccine, I have to convince your immune system that the vaccine itself is a threat worth taking seriously.

This can be accomplished in a number of ways. One is to inject a weakened what immunologists call attenuated or even killed version of a pathogen. This approach has the benefit of looking almost identical to the real pathogen, triggering many of the same danger signals and often resulting in strong, long-term immunity, as is seen in polio vaccination. It can also be risky if you havent weakened the pathogen enough and roll out the vaccine too fast, there is a possibility of unintentionally infecting a large number of vaccine recipients. In addition to this unacceptable human cost, the resulting loss of trust in vaccines could lead to additional suffering as fewer people take other, safer vaccines.

A safer approach is to use individual components of the pathogen, harmless by themselves but capable of training your immune system to recognize the real thing. However, these pieces of the pathogen dont often contain the danger signals necessary to stimulate a strong memory response. As a result, they need to be supplemented with synthetic danger signals, which immunologists refer to as adjuvants.

To make vaccines more effective, whole labs have been dedicated to the testing and development of new adjuvants. All are designed with the same basic purpose to kick the immune system into action in a way that maximizes the effectiveness and longevity of the response. In doing so, we maximize the number of people that will benefit from the vaccine and the length of time those people are protected.

To do this, we take advantage of the same sensors that your immune system uses to sense damage in an active infection. That means that while they will stimulate an effective immune response, they will do so by producing temporary inflammatory effects. At a cellular level, the vaccine triggers inflammation at the injection site. Blood vessels in the area become a little more leaky to help recruit immune cells into the muscle tissue, causing the area to become red and swell. All of this kicks off a full-blown immune response in a lymph node somewhere nearby that will play out over the course of weeks.

In terms of symptoms, this can result in redness and swelling at the injection site, stiffness and soreness in the muscle, tenderness and swelling of the local lymph nodes and, if the vaccine is potent enough, even fever (and that associated generally crappy feeling).

This is the balance of vaccine design maximizing protection and benefits while minimizing their uncomfortable, but necessary, side effects. Thats not to say that serious side effects dont occur they do but they are exceedingly rare. Two of the most discussed serious side effects, anaphalaxis (a severe allergic reaction) and Guillain-Barr Syndrome (nerve damage due to inflammation), occur at a frequency of less than 1 in 500,000 doses.

Early data suggest that the mRNA vaccines in development against SARS-CoV-2 are highly effective upwards of 90%. That means they are capable of stimulating robust immune responses, complete with sufficient danger signaling, in greater than nine out of 10 patients. Thats a high number under any circumstances, and suggests that these vaccines are potent.

So lets be clear here. You should expect to feel sore at the injection site the day after you get vaccinated. You should expect some redness and swelling, and you might even expect to feel generally run down for a day or two post-vaccination. All of these things are normal, anticipated and even intended.

While the data arent finalized, more than 2% of the Moderna vaccine recipients experienced what they categorized as severe temporary side effects such as fatigue and headache. The percentage of people who experience any side effects will be higher. These are signs that the vaccine is doing what it was designed to do train your immune system to respond against something it might otherwise ignore so that youll be protected later. It does not mean that the vaccine gave you COVID-19.

It all comes down to this: Some time in the coming months, you will be given a simple choice to protect yourself, your loved ones and your community from a highly transmissible and deadly disease that results in long-term health consequences for a significant number of otherwise healthy people. It may cost you a few days of feeling sick. Please choose wisely.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Vaccines against the coronavirus will have side effects and thats a good thing - PBS NewsHour

Shawn stepped into the UCLA Vine Street Clinic in Hollywood with confidence. He offered up his arm. The UCLA doctor injected him. It took seconds; there was barely a sting.

Twenty-four hours after the first of two shots, given 28 days apart, he suffered the headaches and fatigue associated with a milder case of COVID-19. But Shawn remained calm, resolved to honor the memory of his mother, a nurse who had died in May 2020 from an unrelated cause.

The 57-year-old nonprofit worker had been thinking about the challenges of COVID-19 for a long time, and he decided to go through the lengthy consent process for the medical trial. It gave me something to do with my anger that was so much better than yelling at someone for not wearing a mask, he says. And [at UCLA] I felt I was in good hands.

Shawn is one of many volunteers who have stepped up to participate in medical trials at UCLA, which is part of a global network thats determined to help find a vaccine against the novel coronavirus.

The stakes are huge. More than 250,000 Americans have already died, and there have been more than 1 million deaths around the world. Economies have been brought to their knees, social tensions have disrupted communities and emotional maladies are on the rise.

In response, doctors and scientists have been challenged to be resilient and ingenious. Theyre taking an array of different approaches, knowing that public confidence in vaccines hangs in the balance.

In addition, it has been a challenge to create a vaccine in such a short amount of time similar efforts have taken five to 10 years. Pharmaceutical giant Pfizer and biotech firm Moderna have both reported remarkable progress, announcing in November that their vaccine candidates were more than 90% effective. All of which has raised questions about the next steps, such as how the vaccines will be distributed.

I dont want to make a vaccine to protect against mild disease, says Dr. Marcus Horwitz, distinguished professor of medicine and microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. I want to protect people who are going to get severe disease.

Horwitz has already developed vaccines against the bacteria behind tuberculosis, anthrax and the tick-borne disease tularemia, but he has never tried to create a vaccine against a virus. When faced with a worldwide pandemic, we thought we might be able to make a contribution, he says.

Vaccines work by training the immune system to recognize and fight disease-causing pathogens, such as viruses or bacteria. Doctors introduce the bodys immune system to antigens, which are molecules from the virus or bacteria, and the immune system responds by making proteins called antibodies and immunity-building T cells, which both neutralize the pathogen.

The delivery of these antigens requires a delicate calculus: It must provoke the immune system, but not go so far as to make the patient ill. You need a vector that will wake up the immune system of the host, but not cause any further harm, Horwitz says.

The vaccine approach by Horwitz and his team, including lead investigator Qingmei Jia, is a medical outlier: They adapted an existing antibacterial platform to build protection against SARS-CoV-2, the virus that causes COVID-19. The team has shown that their vaccine candidate protects hamsters, which develop severe disease in a way similar to humans.

Some of the potential vaccines for SARS-CoV-2 use a weakened form of an adenovirus, which causes the common cold, to deliver the S protein that is found on the surface of the SARS-CoV-2 virus. Horwitzs vaccine stands out from the pack because it uses a weakened bacterium to deliver two SARS-CoV-2 proteins, the M and N proteins.

That difference could have a tremendous impact. Billions of COVID-19 vaccine doses are needed, and bacteria, unlike viruses, are easy and cheap to produce and transportable.

The success of a COVID-19 vaccine also depends on the immune system, which can be less robust in older people.

This is a problem that has driven Song Li, chair of the bioengineering department at the UCLA Samueli School of Engineering, who has focused his career on cell and tissue engineering. Adapting a concept from cancer immunotherapy, Li is developing a biomaterial vaccine booster using artificial cells that could improve the immune systems ability to generate long-term protection.

When the immune system encounters a destructive pathogen, it produces cells that are designed to attack the invader. A small number of those cells, called T memory stem cells, can stay in the system for years ready for a future invasion. Unfortunately, our ability to produce T memory stem cells declines as we get older. Li hopes his booster, in combination with a vaccine, can help fragile immune systems effectively fight against the SARS-CoV-2 virus.

My goal at the outset was to help the elderly population, Li says. But it could be useful for any person whose immune system needs help generating protection from the virus.

Another UCLA team led by Bogdan Pasaniuc, Dr. Manish Butte and Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics at the Geffen School of Medicine is trying to find out why the virus significantly impacts some, but leaves others relatively unscathed.

We know age is a major factor, but we see older people who get infected and do quite well, Geschwind says. We have a limited ability to predict how sick someone will get. His team hopes that studying whole-genome sequences from thousands of COVID-19 patients will reveal hidden factors that make some more vulnerable than others. The research could help identify people who are at higher risk for infection as well as develop new treatment and prevention strategies.

Dr. Brigitte Gomperts, professor of pediatrics and pulmonary medicine and a member of the UCLA Broad Stem Cell Research Center, is studying how COVID-19 affects lung tissue. By using stem cellderived clusters of lung cells, known as organoids, she can rapidly screen thousands of prospective treatments. Because the organoids are grown from human cells and reflect the cell types and architecture of the lungs, they can offer insights into how the virus infects and damages the organ.

At UCLA medical centers around Los Angeles County, physicians are ensuring that their medical trials include diverse groups of people and women of all ages.

COVID-19 has hit the African American and Latino communities particularly hard, says Dr. Jesse Clark, associate professor-in-residence in the department of medicine at the Geffen School of Medicine. We have to make sure that any vaccine has been determined to be safe and effective in all populations that will receive it.

COVID-19 has hit the African American and Latino communities particularly hard. We have to make sure that any vaccine has been determined to be safe and effective in all populations that will receive it.

Dr. Jesse Clark, associate professor-in-residence in the department of medicine at the David Geffen School of Medicine at UCLA

Clark is medical director of the UCLA Vine Street Clinic, which is involved in the Moderna clinical trial. Notably, Modernas vaccine works differently from a typical vaccine, because it doesnt contain the virus at all. Instead, it uses messenger RNA, or mRNA, which uses the bodys genetic code to produce antibodies against the virus.

CNN mentioned that the vaccine trials were having trouble finding minorities to participate, says Roderick, a 37-year-old IT manager and father of two, who is participating in the Moderna trial. Being Black and Mexican, and knowing how hard my demographic has been hit, I just went ahead and signed up online. Its worth doing to help out.

Meanwhile, Dr. Katya Corado, an infectious disease specialist at Harbor-UCLA Medical Center in Torrance, has been enrolling patients in a phase 3 clinical trial of an adenovirus vector vaccine thats under development by the University of Oxford and the biopharmaceutical company AstraZeneca.

All vaccines undergo three phases of clinical trials, according to rules set by the Food and Drug Administration. Phase 1, which involves 20 to 100 volunteers, tests the safety and dosage of the vaccine. Phase 2 tests the drugs efficacy and side effects among several hundred participants, and phase 3 gathers more information about a vaccines safety and effectiveness by studying thousands of volunteers.

In the phase 3 trial, we focus on studying how effective the vaccine is in populations that need it most, Corado says.

Clark and Corado are both hopeful that their work can protect the most vulnerable, which includes people over 65, patients with chronic conditions, those facing economic disadvantages and essential workers.

Inoculations have eradicated past epidemics, such as smallpox. But public faith in vaccines has wavered, especially when a now-disproven report in 1998 suggested that the measles, mumps and rubella vaccine was linked to autism spectrum disorder. That has led to U.S. outbreaks of measles, which had been previously eliminated. So scientists recognize the importance of getting the COVID-19 vaccine right.

There are other factors to consider as well. Vaccine distribution will be high on the agenda of the incoming White House administration, but if supply is limited, the Centers for Disease Control and Prevention recommends prioritizing certain groups, such as medical workers.

Also, some vaccines currently in development need to be stored in ultra-cold conditions. For example, Pfizers vaccine must be stored at minus 70 degrees Celsius, while Modernas vaccine must be kept at minus 20 degrees Celsius the temperature of a regular freezer. These factors will affect how the vaccines are distributed.

Some lawmakers have advocated letting the virus run its course in the hopes of achieving herd immunity, which is when enough people have become immune to an infectious disease, either through being infected or vaccination. Since the COVID-19 vaccine is still pending, a majority of people will need to be infected in order to achieve herd immunity and that comes at a terrible cost.

According to Dr. Robert Kim-Farley, professor-in-residence of epidemiology at the UCLA Fielding School of Public Health, up to 2 million Americans would have to die before the country reached herd immunity.

He argues that vaccines work, even if they are not perfectly safe or perfectly effective, as proven by the near-eradication of polio. But approving vaccines prematurely to buckle under the pressure of politics or profit could cause a terrible backlash against being vaccinated, which could lead to future outbreaks.

We want to make sure we are not cutting corners, Kim-Farley says, that we are getting the best vaccine that has the highest efficacy, the longest duration, the fewest number of side effects [with] the fewest number of doses.

This is a very high-stakes game, and its important to get it right, without recalls or playing into the [anti-vaccination] narrative. What still concerns me is the equitable distribution of vaccines to make sure that countries that are not as wealthy as us have access to these life-saving vaccines. We are all members of one global community.

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Anatomy of a vaccine: What it takes to create a safe, effective COVID shot - University of California

The new collection includes Immune Therapy, Stress Therapy, and Gut Therapy that synergistically nourish the gut microbiome, nervous system, gut-lung axis, and gut-brain axis.

The formulations are the culmination of immune research and over four decades of experience from Co-Founder Paul Schulick. As the companys formulator, Schulick launched For The Biome after parting ways with New Chapter, a company he founded in 1982 which was later acquired by Procter & Gamble in 2012.

We identify For The Biome as a wellness company and although we launched with skincare, my intention has always been to expand into ingestibles. We like to say that you have to treat as a whole to heal as a whole so its only natural that we offer products designed for internal and topical use. The choice to move into immunity was simply nature calling. It was an opportunity to make a contribution, which is what I am here to do, said Schulick.

The master herbalist explained that the products target specific biomarkers to bring an exhausted or overactive immune system back to balance.

We looked at a panel of cytokines, both pro and anti-inflammatory, and a window of immediate effects and response to the exposure of the products. We wanted to see the acute effects and what was moving the needle, said Schulick.Examples of the biomarkers include IL-1B, IL-Ra., IL-2, CD69, CD25, and G-CSF, which help modulate inflammation, signal an immune response, and support renewal. We also looked at the CAP-e antioxidative capacity for the product, or its ability to get into the cells and protect them from the inside out.

Schulick said the Immune Therapy and Stress Therapy are both backed by clinical studies and the probiotic strains in Gut Therapy are backed by several clinical studies as well, adding, We invest heavily to conduct ongoing research and will share this with our customers as it breaks.

In-vitro testing suggests that Immune Therapy balances immunomodulating markers within 2 hours as it coats the mouth and gut microbiome with a protective liquid infusion.

Stress Therapy is a restorative infusion that delivers stress relief by soothing the immune system, nervous system, and supporting the gut microbiome.

The company said Gut Therapy is a first-to-the-world fermentate featuring clinically studied prebiotics, postbiotics, para-probiotics, and live probiotics that support a resilient gut microbiome and its connection to immune, respiratory, and emotional health.

We select the most healing and restorative prebiotic, whole-food, and certified organic botanicals for the digestive system (eg., flax, chaga, aloe, and moringa) and then utilize the power of fermentation to further amplify their benefits. This is no ordinary fermentation process. It is a dual-stage process using the yeast Saccharomyces cerevisiae and two of the most researched probiotic strains from Lactobacillus and Bifidobacteria genera, GG and BR03. These strains produce many important immunologically active peptides also known as postbiotics.

Schulick added that Gut Therapy then completes the formulation with a therapeutically validated, live dose of Lactobacillus plantarum DR7, a probiotic with multiple positive effects on immunity (NK cell upregulation, respiratory protection), stress response (cortisol, serotonin) and cognition (enhanced learning and social emotional reasoning).

When formulating these products, I referenced groundbreaking research that focused on advancements in immune support around the world. This research, coupled with my passion for herbalism, guided me as I chose plants, mushrooms, and probiotics renowned for their ability to support a wiser immune response.

Schulick told NutraIngredients-USA that his goal was to source the best possible forms of these components and introduce some of them for the first time to North America. One of the most remarkable is the herb Cistus incanus, popular in the Mediterranean, and known for its remarkable restorative and protective abilities. Its featured in Immune Therapy because of its notable ability to signal immune response and recovery. Whats more is that, while this ingredient is phenomenal on its own, its even more effective when paired with symbiotic nutrients. We saw increased activity of Cistus incanus when we paired it with vitamin C-rich black currant leaves and rose hips, and birch-grown chaga with betulinic acid. All three of our formulas deliver these kinds of extraordinary synergies.

Schulick said identifying the ingredients is the easier part. Getting the level of efficacy and quality that meets our standards is another story.

For the most part, this has always been the case, COVID or not. Certainly, this period of time during COVID has made that more difficult and weve had to search around the world two or three times, sometimes, to find what we needed. We then independently test and confirm for levels of active compounds to deliver what we are seeking.

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For the Biome makes leap from skin to immune health - NutraIngredients-usa.com

December 2, 2020

Arizona State University has been awarded a $12.5 million multiyear subcontract from the Frederick National Laboratory for Cancer Research (FNL), operated by Leidos Biomedical Research on behalf of the National Cancer Institute, to join the NCIs Serological Sciences Network (SeroNet), the nations largest coordinated effort to study peoples immune response to COVID-19.

SeroNet was enacted as a result of $306 million in emergency supplemental funding from the U.S. Congress for the NCI to study serological sciences related to COVID-19.

ASU is one of just four Capacity Building Centers (CBCs) selected nationally for SeroNet. The goal is to develop high performance serological tests to determine a persons previous exposure to SARS-CoV-2. The network aims to combat the ongoing COVID-19 pandemic by improving the ability to test for an antibody response to infection, especially among diverse and underserved populations, and to accelerate the development of treatments and vaccines aimed at preventing COVID-19 and improving patient outcomes.

This award will now establish Arizona State University as the most comprehensive COVID testing research center in the Southwest, and is a testament to our commitment and scientific capabilities to be offered the opportunity to join SeroNet and to provide a critical service to our community and nation, said ASU Biodesign Institute Executive Director Dr. Joshua LaBaer. It builds upon the great successes of our innovative antibody testing platform, robust biomarker discovery and diagnostic assay development capabilities; our extensive experience at successfully completing large federal contracts, grants and FDA emergency use authorizations; and our response to this pandemic through large-scale PCR-based SARS-CoV-2 testing of saliva samples.

According to ASU Biodesign Institute Executive Director Dr. Joshua LaBaer, ASU hopes to develop a simple, FDA-approved COVID-19 antibody test to detect for previous SARS-CoV-2 exposure and to better understand a persons immune response to COVID-19.

The NCI, FNL and ASU were able to pivot to support COVID-19 research because of their deep experience in virology and immunology research, including research on viruses that cause cancer, such as HPV, and experience in immunotherapy.

In March, LaBaer, a medical oncologist by training who co-discovered breast cancer biomarkers included in a CLIA-approved breast cancer test with colleague Dr. Karen Anderson, shifted his laboratory to become a CLIA-certified clinical laboratory to fully support COVID-19 testing.

In May 2020, LaBaer and Vel Murugan, an ASU associate research professor and co-principal investigator on the SeroNet CBC subcontract, created the first saliva-based COVID-19 test in the Western United States.

To date, ASU has provided more than 300,000 free saliva tests to the general public, first responders, doctors, nurses and medical personnel, and the entire ASU community to help Arizona in the response to keep individuals safe and healthy during the pandemic.

As part of the national SeroNet, ASUs interdisciplinary team of expert scientists and researchers at the Biodesign Institute, led by LaBaer, will establish the ASU Biodesign Capacity Building Center (ABCBC). Other key individuals involved in this project are Ji Qiu, Jin Park, Femina Rauf, Lusheng Song, Mitch Magee and Michael Fiacco.

Through this latest project, we hope to develop a simple, FDA-approved COVID-19 antibody test to detect for previous SARS-CoV-2 exposure and to better understand a persons immune response to COVID-19, said LaBaer. We ultimately want to develop a test for any exposures people may have had to all known human coronaviruses and other respiratory pathogens in order to improve patient outcomes.

The core of the technology builds upon a novel ASU platform (called MISPA) that uses rapid DNA sequencing to monitor many patients immune responses to multiple viral proteins simultaneously, via a molecular barcoding. ASU has tested the platform on cancer subtypes caused by HPV. Now, they want to adapt the same technology for understanding COVID-19.

This system exploits the power of DNA next-generation sequencing (NGS) technology to quantify COVID virus antigens and their interactions with antibodies produced in the body to fight the infection, said Murugan. With this assay, we 'barcode' individual proteins called antigens within the virus with unique DNA sequences that interact in solution with patient serum, followed by quantification of the antibody-bound barcodes by NGS.

Unlike current commercially available serological tests, the MISPA-based test is designed to be quantitative about the strength of the immune response while providing information about responses to multiple proteins and eventually, multiple viruses simultaneously. In addition, because individual reactions can also be indexed (or barcoded) in parallel, thousands of patient samples can be combined, and all the results determined in a single NGS run (many barcoded patients versus many barcoded proteins).

MISPA will also be deployed through a similar high-throughput, fully automated test that can process thousands of samples per day as we have successfully demonstrated from our COVID-19 saliva test, said Murugan.

Initial tests will rely on a testing pool of individuals who have recovered from the infection. Potential sites for serological tests include: ValleyWise, Midwestern/Abrazo hospital networks, Dignity Health hospital network, Columbia University, Colorado River Indian Tribal community through their tribal government, ASU students and population, other universities in Arizona and essential infrastructure partners.

Should the test validation and FDA EUA become approved, testing will expand to essential infrastructure employees, health care professionals and residents in long-term care facilities or other congregate living settings, including prisons and shelters. Community surveillance for asymptomatic population will be conducted at a lower priority when needed.

The lessons learned from ASUs role in SeroNet research could be applied immediately to the COVID-19 pandemic crisis and may prove valuable to public health beyond the pandemic.

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ASU receives $12.5M subcontract to better understand COVID-19 immune response and improve patient outcomes - ASU Now

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While having a robust immune response to coronavirus infection may sound helpful, a new study shows the opposite may be true.

To better understand how variations in early host immune responses affect disease outcomes, researchers at the Tulane National Primate Research Center followed the course of disease in the four weeks following COVID-19 infection in non-human primates.

They discovered robust early immune responses to the virus and a recruitment of immune cells from the blood to the lungs. They also found that certain cytokinei.e., cell-signaling proteins that help to regulate pro- and anti-inflammatory responsesmay prove helpful in predicting disease outcomes.

These results suggest that in these early weeks post-infection, the stronger the initial host immune response, the worse the disease outcome, says Monica Vaccari, associate professor of microbiology and immunology at the Center and lead author of the study in Nature Communications.

Vaccari explains that while the body mounts a pro-inflammatory innate immune response as a first line of defense to protect against the spread of infection and heal damaged tissue, it is a dysregulated or over-reactive immune response that can cause severe damage. Too much inflammation in the lungs, for example, can result in decreased oxygen.

A pro-inflammatory response is usually our bodys first line of defense, and it can be a very helpful mechanism. But what were seeing with coronavirus infection is that somewhere down the line, there is uncontrolled inflammation. We want to know when and why this happens, Vaccari says.

Understanding what happens in the immune system during this short period following infection will be essential in developing effective therapeutics against COVID-19. While immune functions can be modulated, scientists want to avoid turning off immune responses that may be critical to fighting infection.

One of the most vexing aspects of the novel coronavirus is the broad spectrum of disease outcomes associated with it. A disease that causes few or mild symptoms for most also has the capacity to cause severe and lasting damage or death for others.

While scientists and clinicians have long suspected that it is the hostor person that acquires the diseasethat dictates disease severity, they have not known which specific individual immune markers are harmful and which are protective, particularly in the earliest stages of disease.

This new study identified variations in early host immune responses that may be predictive of COVID-19 disease severity.

Source: Tulane University

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Stronger early immune reaction might make COVID worse - Futurity: Research News

By Graham Lawton

Ted Shaffrey/AP/Shutterstock

UK regulators have authorised a covid-19 vaccine created by Pfizer and its partner BioNTech for emergency use, meaning that vaccine rollout is planned to begin soon. Here, we answer questions about the science of the vaccine, who will get it first, how confident we can be in the authorisation process and the logistics of vaccinating everyone in the UK.

How effective is the vaccine?About 95 per cent. The phase 3 trials of the Pfizer/BioNTech vaccine involved 42,000 people, about half of whom got the experimental vaccine and the rest a placebo. In total, 170 people fell ill with covid-19. Only eight of them were in the vaccine group; 162 had received the placebo. So around 5 per cent of cases were in the vaccine group, which is where the 95 per cent figure comes from. That is a very healthy number: the World Health Organization (WHO) has said it would be happy with 50 per cent.

What is in the vaccine?The active ingredient is messenger RNA that carries instructions for making the viruss spike protein, which it uses to gain entry to cells. The mRNA is synthetic, not extracted from actual viruses. It is delivered in a tiny sphere of inert fatty material called a lipid nanoparticle.

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The RNA-bearing nanoparticles are suspended in saline solution and injected into muscle tissue in the upper arm. The mRNA is then taken up by specialist immune cells, which follow its instructions to make the spike protein, just as they would do if they had become infected with the actual virus.

The spike protein is recognised as foreign by the immune system, which mounts an attack against it. Antibodies, B cells and T cells are activated, according to Uur ahin, the chief executive of the small German company BioNTech that co-developed the vaccine with US drug giant Pfizer. An immune memory is also laid down, he says, which means the immune system has learned how to defeat the pathogen and is primed to mount a swift response if it encounters the coronavirus again.

How long does the immune memory last?Its hard to say at this point, because the clinical trials werent set up to answer that question, and in any case, they only began dispensing second doses of the vaccine four months ago. The WHO says that a minimum of six months would be acceptable. It will become clearer as time marches on and the volunteers continue to be monitored. Sahin says he expects protection to last months or even years. Given what we know about natural immunity that looks about right, says Eleanor Riley at the University of Edinburgh in the UK. She envisages people needing annual boosters, at worst.

How long does it take for immunity to develop fully after vaccination?The trial began assessing immunity seven days after the second shot. We know that protective immunity builds up within four weeks of the first dose, but Sahin says that it appears to develop earlier than that. Further details will be published in a matter of days, he says.

What happens to the mRNA in the body?It is active for a few days then decays rapidly.

Its a two-shot vaccine, so what happens if people miss their second shot? Is a single shot still protective?Two shots are needed, and the second shot is required to attain immunity. The gap between doses in the trial ranged between 19 and 42 days. Only 2 per cent of people in the trial missed their second dose so it isnt entirely clear what happens under those circumstances.

Are there any side effects?Sometimes, but they are mild. In the trial, the vaccine was generally well-tolerated, and an independent data monitoring committee reported no serious safety concerns. The worst side effects were fatigue and headaches after the second dose. About 4 per cent of people reported fatigue and 2 per cent a headache. Other side effects were pain at the injection site and muscle pain. These are common reactions you would have with vaccination, says zlem Treci, chief medical officer at BioNTech. Older adults reported fewer and milder side effects.

Does it work in older people?Yes. Trial participants were aged up to 85, and the efficacy in people over 65 was 94 per cent a tiny bit lower than the overall number but still very protective, and much higher than some vaccine experts feared. The vaccine hasnt been tested in people aged over 85.

What about other vulnerable groups?The vaccine appears to be equally effective regardless of recipients age, sex and ethnicity, according to BioNTech. It has been tested extensively in people who have already had the virus and doesnt cause any ill effects. It has also been tested in people with stable pre-existing conditions also known as comorbidities including diabetes, cancer, hepatitis B, hepatitis C and well-managed HIV. Their response was as good as anyone elses.

People with serious or worsening comorbidities will also be eligible for the vaccine. BioNTech says it has data on this group and will release it in a matter of days.

Does it protect everyone?No. In the trials, out of about 20,000 people who were given the vaccine, eight caught covid-19 and one became seriously ill. In contrast, 164 people who received the placebo fell ill, nine severely. It isnt known why some people didnt respond to the vaccine. But a success rate of 95 per cent is about as good as it gets with any vaccine.

Does it stop people from catching and transmitting the virus?We still dont know. The trial was designed to test for symptomatic covid-19 and confirmed infection with the virus. Assessing whether the vaccine prevents transmission which is probably a prerequisite for attaining vaccine-induced herd immunity is much harder. But Pfizer says it is carrying out more studies on this important question and will release information soon.

Some vaccines can paradoxically make a disease worse through a process called antibody-enhanced disease. Is that a risk?Yes, theoretically. But it hasnt been seen with this vaccine or any other against covid-19, and hasnt occurred naturally, as sometimes happens with other viruses.

Has the the full data from the trial been published yet?No, it hasnt, but there is nothing sinister about that. Companies can release news to the market as soon as they have it, which is a much speedier process than preparing a scientific manuscript. According to Pfizer, every last detail of the science will be submitted to a top-ranking peer-reviewed journal as soon as it is ready. It will then be up to the journal how long it takes to publish.

Who is first in the queue in the UK?When a vaccine is approved it is customary to first offer it to people who took part in the clinical trial but received the placebo. However, as the trial wasnt done in the UK, there is nobody in this category.

Care home residents and their carers have the highest priority, according to a priority system devised by the UKs Joint Committee on Vaccination and Immunisation. But there are problems with delivering this particular vaccine to care home residents because it needs to be transported at very cold temperatures in special cases that carry around 1000 doses. These cases cannot be broken up for distribution, which makes it very hard to get the required doses into individual care homes.

Next in line are people aged over 80 and frontline healthcare workers, followed by people aged over 75, then people in increasingly younger age groups and/or with underlying health conditions.

Will anyone be excluded from the vaccine programme?Yes. Pregnant women and children under 16 wont be eligible, at least at first. The vaccine hasnt been tested on pregnant women or children under 12, and there isnt enough data on children age 12 to 15. But trials in those groups are ongoing or planned.

Everyone else can get it?Yes, but most will have to wait their turn. According to Sean Marett at BioNTech, the exact delivery schedule depends on how fast the factories can churn it out and where else the vaccine is approved, as the company is committed to equitable access. We will deliver as many doses as we can as quickly as we can, he says.

What does temporary authorisation for emergency use mean?Exactly what it says on the tin. The UKs Medicines and Healthcare products Regulatory Agency (MHRA) has expedited the approval process in recognition of a public health emergency, and could rescind the approval just as quickly. But that is highly unlikely as it says it has done a thorough assessment of the safety and efficacy data and has seen nothing to give it reason not to approve.

Will the vaccine inevitably progress from temporary to full authorisation?Probably, but it isnt a given. Pfizer says it expects so, but that is in the hands of the regulators.

It all happened very quickly, can we be confident corners werent cut?Yes. The MHRA is an independent body and so is the Commission on Human Medicines, which also had a say in the decision to approve the vaccine in the UK. Even though the MHRA only received the full clinical trial data just over a week ago, the vaccine developers have been submitting information since October, which has been subject to ongoing review.

The European Medicines Agency, the drug regulator that approves covid-19 vaccines for the European Union, said in a statement that its process for assuring the safety and efficacy of the vaccine is based on more evidence and more checks than the emergency authorisation used in the UK.

According to the vaccine developers, the MHRA asked for exactly the same amount of information as any other regulatory agency. It has been working 24/7 to assess it, says Treci.

Are other countries likely to approve the vaccine soon as well?Yes. Pfizer/BioNTech have also applied for approval in the US, EU, Australia, Canada, Japan and New Zealand, and say they are preparing to submit applications to other regulatory agencies around the world. Decisions are expected from the US and EU this month.

How many doses is the UK getting?In total, the UK government has pre-ordered 40 million single doses, which is enough for 18 million people assuming double dosing and about 10 per cent wastage. But it wont get all 40 million at once. The full order will be delivered in batches over the course of 2020 and 2021.

When will the vaccine reach the UK?The first batch is currently being packaged at Pfizers vaccine factory in Puurs, Belgium, and will be dispatched to the UK by lorry and plane as soon as it is ready possibly as early as the coming weekend. UK health minister Matt Hancock has said he expects the UK to receive 800,000 doses over the next few days.

When will vaccination start?Again, as soon as possible.

Doesnt the vaccine require complicated cold storage?Yes and no. For long-term storage meaning for six months or so the vaccine has to be kept at -70 C, which requires specialist cooling equipment. But Pfizer has invented a distribution container that keeps the vaccine at that temperature for 10 days if unopened. These containers can also be used for temporary storage in a vaccination facility for up to 30 days as long as they are replenished with dry ice every five days. Once thawed, the vaccine can be stored in a regular fridge at 2C to 8C for up to five days.

Could the supply chain be disrupted by the UKs formal departure from the EU as of 1 January?Possibly. But according to Marett, if there is disruption we will find another route.

Where will people be vaccinated?The usual places: GP surgeries, health centres and hospitals. People will be invited by the NHS. The entire supply is going to the various NHS bodies in the UK and nobody will be able to jump the queue by buying a vaccine privately, according to Pfizer.

Could something still go wrong?Yes, but that is highly unlikely. Vaccine effectiveness in the real world is almost always lower than efficacy in trials, but the drop-off would have to be spectacular to dip below the 50 per cent threshold accepted by the WHO.

There could still be rare severe adverse effects down the road, especially as mRNA vaccines are a new technology and have never been rolled out on a massive scale before.

Vaccine clinical trials arent big or long enough to rule out rare but serious side effects, which sometimes appear months or even years after vaccination. People who have been vaccinated will be followed up for two years to ensure that there are no serious adverse effect waiting in the wings.

But these are small, theoretical risks. As Fiona Watt at the UK Medical Research Council (MRC), said: This is great news.

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Everything you need to know about the Pfizer/BioNTech covid-19 vaccine - New Scientist News

For the first time, researchers have demonstrated how the gut microbiome the community of microorganisms living in the gut can influence the immune system in humans. Their work could lead to new treatments for immune-related conditions.

The researchers at Memorial Sloan Kettering Cancer Center in New York, NY, tracked the recovery of patients gut microbiota and immune system after bone marrow transplants (BMTs) following treatment for blood cancers.

Healthcare professionals use chemotherapy and radiation therapy to destroy cancerous blood cells in conditions such as leukemia and lymphoma. After completion of the treatment, which also kills healthy immune cells, specialists inject patients with stem cells from a donors blood or bone marrow.

These donated cells slowly restore patients ability to make their own blood cells.

However, patients have to take antibiotics in the first few weeks after the transplant because they are still vulnerable to infections. These upset the balance of their gut microbiota, killing friendly bacteria and allowing dangerous strains to thrive.

Once patients immune systems are strong enough, they can stop taking the antibiotics, which allows their gut microbiota to recover.

The researchers at Sloan Kettering used this unique opportunity to study how the microbiota affects the immune system.

The scientific community had already accepted the idea that the gut microbiota was important for the health of the human immune system, but the data they used to make that assumption came from animal studies, explains systems biologist Joao Xavier, who is co-senior author of the paper with his former postdoc Jonas Schluter.

The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyze the associations between these two systems, says Dr. Schluter, who is now an assistant professor at NYU Langone Health in New York, NY.

Using blood and fecal samples from more than 2,000 patients treated at the cancer center between 20032019, the researchers were able to track daily changes in their gut microbiota and the number of immune cells in their blood.

Our study shows that we can learn a lot from stool biological samples that literally would be flushed down the toilet, says Dr. Xavier. The result of collecting them is that we have a unique dataset with thousands of data points that we can use to ask questions about the dynamics of this relationship.

The researchers used a machine-learning algorithm to identify patterns in the data, which included information about patients medications and the side effects they experienced.

One of the findings was that the presence of three types of gut bacteria called Faecalibacterium, Ruminococcus 2, and Akkermansia was associated with increased blood concentrations of immune cells called neutrophils.

By contrast, two types called Rothia and Clostridium sensu stricto 1, were associated with reduced numbers of these immune cells.

Computer simulations by the researchers predicted that enriching microbiota with the three friendly genera would speed up the recovery of patients immune systems.

This research could eventually suggest ways to make BMTs safer by more closely regulating the microbiota, says co-author Marcel van den Brink.

The study appears in Nature.

Concluding their paper, the authors write:

Our demonstration that the microbiota influences systemic immunity in humans opens the door toward an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.

A previous study found that having a greater diversity of bacterial species in the gut is associated with a better chance of survival after a stem cell transplant. This research also found that a low diversity of bacteria increased the likelihood of potentially fatal graft-versus-host disease, when the donor immune cells attack the recipients tissues.

In 2018, the Sloan Kettering researchers published results from a clinical trial in which they used fecal transplants to restore patients microbiota after treatment for blood cancer.

They used the patients own fecal matter, which had been collected and frozen before the bone marrow transplant and antibiotic treatment disrupted their gut microbiota.

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Gut bacteria can help rebuild the immune system - Medical News Today

Summary

Tumors with mutations in the BRCA2 cancer-predisposition gene respond better to checkpoint blockade immunotherapy than tumors with mutations in BRCA1, scientists at Memorial Sloan Kettering have found.

Treatments that harness the immune system to fight cancer have greatly improved outcomes for some people with cancer. Scientists are learning more about why some people respond much better than others to these drugs.

One major factor is something called tumor mutation burden (TMB) the number of DNA changes a tumor has. Studies from researchers at Memorial Sloan Kettering and elsewhere have shown that tumors with high TMB tend to respond better to immune checkpoint inhibitors. In 2017, the US Food and Drug Administration approved the checkpoint inhibitor pembrolizumab (Keytruda) for the treatment of tumors with a type of genetic defect called mismatch repair (MMR) deficiency.

Checkpoint inhibitors work by releasing a natural brake on your immune system so that immune cells called T cells recognize and attack tumors.

MMR is one of several DNA repair pathways that cells use to fix mistakes in DNA. Mutations in this pathway lead to faulty DNA repair and therefore to higher TMB. Next to MMR, the most commonly mutated DNA repair pathway is called homologous recombination, which repairs double-strand breaks in DNA (in other words, when both of sides of the DNA ladder are broken). The cancer-predisposition genes BRCA1 and BRCA2 belong to this pathway. When they are mutated, DNA damage accumulates and ones risk increases for developing several types of cancer, including breast, ovarian, prostate, and pancreatic cancers.

Scientists at MSK are now reporting that mutations in one BRCA gene, but not the other, produce tumors that respond well to immunotherapy.

When we started this work, we assumed that tumors with both types of homologous recombination deficiency would respond to immunotherapy based on having a high mutation burden, says physician-scientist Nadeem Riaz. But we found instead that BRCA2-mutated tumors responded much better than BRCA1 tumors.

The unexpected results, which were published November 16 in the journal Nature Cancer, may have implications for the types of treatments that people with BRCA2 mutations should consider.

The researchers made their discoveries using both human data and mouse models. When they compared tumor mutations and clinical information from patients treated with immunotherapy at MSK, they found a direct correlation between mutations in BRCA2 and better survival after treatment.

To confirm that this correlation was more than simply a chance finding, they created genetically engineered mouse models of BRCA1- and BRCA2-mutant breast and colorectal cancers. In both cases, they found that only the BRCA2-mutant tumors responded to treatment with checkpoint inhibitors.

In addition to being surprising, the results were a bit counterintuitive.

Five years ago, people wouldve probably thought BRCA1 was going to be the more immunogenic tumor, Dr. Riaz says. Thats because of the two types, BRCA1-mutant tumors tend to have higher number of immune cells inside them. You might expect that having more immune cells would mean a better response to immunotherapy. But in fact, it was the BRCA2-mutant tumors that showed the better response.

If BRCA1 and BRCA2 are both involved in homologous recombination, and both lead to higher TMB, why is it only the BRCA2-mutants that seem to respond to immunotherapy?

According to the study authors, it may have to do with the type of mutations that each produces. Mutant BRCA2 produces more small deletions in the DNA sequence removing one DNA base letter, of example. These mutations shift the reading frame of genes and change how the DNA sequence is translated into protein. Imagine the gene is a sentence that reads: I like chocolate ice cream. A deletion of one DNA letter might change the sentence to read: I likc hocolatei cec ream. The immune system senses these misspelled proteins as foreign and attacks cells containing them. By contrast, BRCA1 creates different types of mutations, which are not as readily detected by the immune system.

Sometimes we think that we know the biology and know what to expect, but when we investigate in detail using the right tools, the results surprise us.

Jorge Reis-Filho, a physician-scientist in MSKs Department of Pathology and a collaborator on the Nature Cancer study, says the results underscore the importance of testing assumptions. Sometimes we think that we know the biology and know what to expect, but when we investigate in detail using the right tools, the results surprise us, he says.

Often its not what we dont know that get us in trouble, its the things that we think we know for sure that can lead us astray, he adds.

The new publication is the first to emerge from the Precision Radiation Oncology Initiative, which Dr. Riaz leads. Created by the Chair of MSKs Radiation Oncology Department, Simon Powell, the Initiative is geared toward making radiation a type of targeted therapy when used in combination with other treatments such as immunotherapy. Because radiation damages DNA and forces cells to use their DNA repair pathways to fix the damage, the DNA repair defects that cancer cells often have can be exploited against them.

While these new findings need to be confirmed by others and validated in clinical trials, they do suggest that people with BRCA2-mutant tumors may wish to consider enrolling in clinical trials of immunotherapy. Several trials are currently enrolling people with BRCA-mutant cancers.

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For People with Certain BRCA Mutations, Activating the Immune System Could Be Promising Treatment - On Cancer - Memorial Sloan Kettering

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Healthy lifestyle is natural way to boost immune system - WSMV Nashville

Overall, your immune system does an excellent job of defending you against harmful substances, germs and cell changes that could make you ill. However, being mindful of the food and beverages you consume can also help support your immune system and keep you well.

Kelly Springer, a registered dietician and owner of Kellys Choice Nutritional Company says the immune system is very complex and a huge proportion of your immune system is actually in your gastrointestinal tract. The human digestive system has over 100 trillion bacterial cells swimming around and the gut microbiome plays a very important role in benefiting your immune system.

Springer shares some tips on how to keep your gut happy and healthy: eat the right foods, make sure you are hydrated throughout the day, cut out all artificial sweeteners and try to cut back on stress. By following these tips you can affect the health of your digestive system, because its responsible for 70 percent of our immunity.

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Healthy habits to strengthen your immune system and fight off cold, flu and coronavirus (video) - syracuse.com

This article, part 3 in a six-part series on the lymphatic system, discusses its role in protecting the body from invasive pathogens and toxins

The lymphatic system plays an important role in providing immune responses to harmful micro-organisms and toxins that enter the body. This article, the third in a six-part series on the system, discusses its main functions in providing immunity.

Citation: Nigam Y, Knight J (2020) The lymphatic system 3: its role in the immune system. Nursing Times [online]; 116: 12, 45-49.

Authors: Yamni Nigam is professor in biomedical science; John Knight is associate professor in biomedical science; both at the College of Human and Health Sciences, Swansea University.

Potential pathogens (micro-organisms capable of causing disease) are ubiquitous in the environment and can enter the body via the skin (through direct contact, particularly if the epidermis is injured through cuts, grazes or burns), the respiratory system (through inhalation), the gut (through ingestion) and the genito-urinary tract (through sex or the insertion of invasive devices such as catheters). Although each of these sites is protected by unique barriers and defences, some pathogens can breach these preliminary defences and enter the body.

The immune system comprises a range of cells some basic and innate, others extremely specialised to detect and remove pathogens from the body. The lymphatic system works alongside the immune system to destroy unwanted pathogens either locally and directly, or by alerting the whole body to the infection and helping to mount a wider systemic immune response.

The first two articles in this series discussed the role of lymph in supporting the cardiovascular system, and examined the organs and tissues that make up the lymphatic system. This article focuses on the immune function of the lymphatic system.

The spleen is often considered to be a structurally larger version of a lymph node

The immune system includes a vast range of distributed defence cells: these are the leucocytes (white blood cells). The more-basic innate immune leucocytes are the first responders, responsible for immediate and non-specific engagement with a pathogen; they include phagocytes (cells capable of engulfing and absorbing bacteria and other small cells and particles) such as macrophages and dendritic cells, which encounter and indiscriminately eat unwanted microbes or infected cells.

If innate cells cannot deal with the pathogen, more-specialised cells known as lymphocytes need to be introduced to a pathogen to recognise it as a threat, before they can launch an attack on it.

These large-cell phagocytes are derived from monocytes (large phagocytic white blood cells); they can be fixed in tissues or mobile in the blood. Macrophages are capable of reeling in microbes with their cytoplasmic extensions (pseudopods) and engulfing them; they are tough cells that survive well and can perform this function many times over. Macrophages are also able to trap antigens (small molecules found on the surface of all cells) and present them to other leucocytes of the immune system.

Healthy cells in the body contain self-antigens, which act as important flags to prevent the immune system from attacking the bodys own cells. Phagocytes recognise pathogens and the toxins they may produce as foreign bodies by the presence of their different (non-self) antigens; they engulf and sequester (capture/trap) these foreign pathogens, which are then rapidly killed by intracellular digestion.

Lymphocytes are sentinel cells of adaptive immunity; they make up 20-30% of circulating leucocytes and include B-lymphocytes and T-lymphocytes. Bone marrow harbours about 12% of the bodys lymphocytes, whereas the spleen and lymph nodes contain approximately 55% of resident lymphocytes; the remainder are found in other lymphatic organs and tissues. Free lymphocytes in the blood amount to only about 2% of the lymphocyte population (Pabst, 2018).

B-lymphocyte cells (B-cells) are formed and mature in the bone marrow. Once released, they develop the ability to determine which antigens they should react to (immunocompetence) and which are harmless (self-tolerance). Mature B-cells colonise secondary lymphoid organs such as lymph nodes or the spleen and:

Collectively called immunoglobulins (Ig), antibodies are among the most abundant protein components in the blood and an important part of the immune system (Alberts et al, 2015). As a nave B-cell becomes fully mature, it can display thousands of membrane-bound antibodies on its surface, and each B-cell has its own unique set of these ready to identify and bind to a particular antigen. If a random encounter with a potentially pathogenic foreign antigen results in binding and triggering of any of these membrane antibodies, it activates the B-cell.

The B-cell rapidly clones itself, forming masses of B-cells, all with the same instructions for producing the antibody designed to fight that particular antigen. The majority of these cloned cells become B-plasma cells large antibody-producing factories while a small proportion are retained as memory B-cells, able to quickly mass produce the same antibodies again if that particular antigen is encountered in future. Plasma cells are capable of producing around 2,000 antibodies per second (Alberts et al, 2015). They are usually detectable in the humor (plasma) after 4-7days and float freely in blood and lymph, binding to foreign antigens on the surface of the pathogen or to the toxin that triggered their formation.

The role of antibodies. Although they cannot directly destroy antigens or kill pathogens themselves, the action of antibodies can:

First, as antibodies bind to the foreign pathogens, they neutralise them by physically blocking binding sites on the pathogen so it cannot attach to tissue cells and cause disease.

Second, antibodies cause agglutination of pathogens as they can bind to more than one antigen simultaneously. Agglutinated pathogens clump and cannot move around as easily, so it is easier for macrophages to detect and phagocytose them, and for other more-specialised lymphocytes to kill them. This coating of foreign cells by antibody molecules is known as opsonisation and makes the pathogen more attractive to circulating phagocytes.

Finally, when bound to their corresponding antigens, antibodies can activate a system of potent plasma enzymes of the complement system. This group of 20 or so proteins, once activated, forms a protein conglomerate termed a membrane attack complex (MAC) which attacks and ruptures pathogens membranes leading to cell lysis and death. The complement system can be activated by antigen-antibody complexes or recognition of bacteria.

Pathogens are not always found in fluids; many become intracellular (invade the cells) where antibodies cannot reach. Fortunately, another branch of adaptive immunity can provide more direct cell-to-cell combat. This is cell-mediated immunity and is facilitated by the T-lymphocytes (T-cells), which are produced in the bone marrow and mature in the thymus gland (see part 2).

There are a few different types of T-cells, but the two main ones are:

They are able to locate compromised body cells (those that have been hijacked by pathogens or become cancerous). However, T-cells can only do this if they are told to do so by other cells: during phagocytosis, phagocytes ingest and break up pathogens into numerous tiny molecules. Some of these molecules are moved onto grooved proteins, termed major histocompatibility complexes (MHCs), on the surface of the phagocyte and displayed there. Cells that can do this are known as antigen-presenting cells (APCs).

T-cells are unable to recognise whole antigens, but they can recognise parts of them when they are displayed on an APC. Just as nave B-cells carry antibodies on their surface for one specific antigen, nave helper T-cells have receptors that will only bind to one specific combination of MHC and antigen. If these cells meet an APC displaying the correct MHC-antigen match, the helper T-cells will bind to it. Once bound, the helper T-cell is activated and, with the help of chemical messengers (cytokines), quickly clones itself to produce many more helper T-cells and cytokines.

Some of these cytokines now activate cytotoxic T-cells, which can kill marked, rogue cells by releasing potent enzymes that puncture the target cell membrane, resulting in cell death. Cytokines are important molecules in the immune system in particular, interleukin1 plays a significant role in initiating the inflammatory process, acting as the major endogenous pyrogen to promote fever during infection, as well as helping B-cells to rapidly undergo proliferation and clonal expansion.

Helper T-cells also play a crucial role in helping B-cells to become fully activated to produce antibodies. They do this by checking that the antigen presented by B-cells is one the body needs to react to and destroy. In fact, helper T-cells play the most vital role in the provision of immunity.

Dendritic cells. These cells are effective APCs that migrate from the bone marrow into peripheral tissues. They are a pivotal link between the innate immune system and the adaptive immune system. So-called because their surface membrane looks similar to the tree-like dendrites of neurones, dendritic cells are key in activating T-cells by presenting microbial antigens to them. Their wispy extensions and surface pattern recognition receptors recognise common features of many microbial pathogens, making them efficient antigen catchers. Dendritic cells bind to and phagocytose pathogens and, once activated and displaying phagocytosed antigens, migrate from tissue into lymphatic vessels.

As potential sites of infection are infiltrated by a dense network of lymphatic capillaries (see part 1), it is also inevitable that pathogens and/or their antigens will end up circulating in the lymphatic system. Parts1 and part 2 of this series discussed the importance of tissue drainage and the transport of lymph back into the circulatory system to ensure homoeostasis. While lymph is circulating around the body, it passes through various checkpoint sites of the lymphatic system; these sites include lymph nodes, the spleen and various types of mucosa-associated lymphoid tissue (MALT) (Fig 1). The lymph nodes, in particular, play a major role in trapping foreign material.

Approximately 600-700 lymph nodes are situated in clusters around the body in lymphatic vessels; they range from about 1-2mm to 2cm in size and are often palpable in the neck, armpit and groin.

These tightly packed balls of lymphoid cells and protein primarily act to:

The lymph nodes play host to a series of complex cellular interactions that typically lead to activation of residing cells, the lymphocytes and macrophages; depending on what they detect at the lymph node, they can activate locally in the node or activate immunity systemically outside the node.

The structure of lymph nodes is discussed in part2. T-cells are mainly gathered in the paracortex, whereas B-cells cluster primarily in the follicles of the outer cortex. Lymph (carrying invader antigens, either free or bound to dendritic cells) enters nodes via an afferent lymphatic vessel. Macrophages lining the lymphatic sinuses of the lymph node may transfer free antigens to T- and B-cells, which are equipped with receptors that are each capable of recognising specific foreign antigens.

Antigens usually reach the lymph node carried by APCs, which home into the paracortical region and stimulate antigen-specific T-cells (Fig2). If a responsive T-cell encounters a specific antigen on the antigen-presenting dendritic cell, it becomes activated to now proliferate and differentiate into effector T-cells, resulting in enlargement of this T-cell zone. Activated T-cells leave the lymph node via the efferent lymphatic vessel.

Stimulation of B-cells in the primary follicles of the lymph node results in the development of secondary follicles with the formation of germinal centres. Antigen-activated B-cells migrate to the medullary cords, where they differentiate into antibody-producing plasma cells and begin production of specific antibodies (Fig2). Antibodies produced in the course of a humoral immune response also leave the lymph node predominantly via the efferent lymphatic vessel to systemically fight the infection.

The immune system at a lymph node works in synergy to help defeat pathogens; indeed, it has been shown that follicular B-cells can also undergo phagocytosis to acquire antigen to show helper T-cells (Martnez-Riao et al, 2018). Following B-cell activation, antigens are sequestered and memory B-cells home into the germinal centres of the lymph node.

Following the events described above, some noticeable effects may become apparent. As the antibody-producing B-cells begin to proliferate in the germinal centres and T-cells robustly clone into effector T-cells, the scaffolding meshwork of the lymph node (fibroblastic reticular cell network) relaxes and becomes elastic and flexible to support the large number of expanding cells. The affected lymph nodes begin to enlarge and may become palpable and tender. Health professionals use this fact in localising and tracing the origins of infections at the time of diagnosis (Table1). As B-cell action subsides and the T-cells leave the lymph node to travel around the body to fight the infection, the lymph node meshwork returns to its original size.

The spleen plays an important role in mounting a targeted response to invading pathogens. It is often considered to be a structurally larger version of a lymph node. The red pulp that makes up 75% of spleen tissue has a major job of destroying old red blood cells and breaking down haem, while the white pulp is fundamental to the adaptive immune response. In the white pulp, the spleens anatomical structure supports both B- and T-cell activation.

Surrounding the central arteriole bringing blood into the white pulp is the periarterial lymphatic sheath (Fig3), predominantly harbouring macrophages and T-cells. Around the sheath is the marginal zone, containing more macrophages and follicles, which are also fed via a blood capillary. Follicles contain nave B-cells.

The white pulp can mount an immune response to foreign invaders arriving in the blood in a number of ways:

The spleen often enlarges when blood-borne infections are present, but splenic enlargement (splenomegaly) is also associated with other diseases; one example is liver failure, which would affect iron breakdown in the splenic red pulp.

Memory B-cells are able to persist in the body, maintaining memory for a given antigen for decades; they are most abundant in the spleen, making up 45% of the total B-cell population in this organ, but they also recirculate in the blood (Hauser and Hpken, 2015). In the case of an antigen first encountered in the spleen, the memory B-cells produced during the primary response tend to congregate in the splenic marginal zones, where blood-borne antigens may predominantly collect. In response to an antigen first encountered in a lymph node, some of the memory B-cells produced remain in the follicle of the lymph node and are ready to react rapidly if the antigen is ever conveyed again to the lymph node. However, other memory B-cells may leave the original lymph node and enter the blood, circulating among the bodys chain of lymph nodes and maintaining peripheral surveillance for the antigen (Mak et al, 2014).

The spleen and lymph nodes are not the only lookout points of the body. Mucosa-associated lymphoid tissue is a form of diffuse lymphoid tissue, an arrangement of lymphoid cells and protein, found in mucous membranes outside the lymphatic vessels. It is strategically positioned at entry points of particularly sensitive tissue, such as the respiratory and gastrointestinal tracts, and includes:

The tonsils are the largest aggregates of lymphatic tissue located in the pharynx; together, they form a ring of tissue (Waldeyers tonsillar ring) that is ideally situated to remove pathogens from the air or food before they can enter the lungs or gastrointestinal tract. As a result of stimulation by pathogens here, sore throats and swollen tonsils are often a visible and painful sign of a viral or other infection.

One part of GALT, Peyers patches, are nodules of lymphoid tissue situated in the distal portion of the small intestine. Another, the appendix, situated at the entrance of the large intestine, contains lymphoid tissue that can destroy bacteria to prevent it breaching, or being absorbed by, the intestinal wall. In both GALT and BALT, mucosal epithelium is scattered with cells known as M-cells, which can trap antigens, small particles or entire micro-organisms and deliver them from the lumen to macrophages and dendritic cells beneath the epithelium. These, in turn, activate B-cells and T-cells lying under the epithelium in the mucosal tissue, which proceed to deal with them through the humoral and cellular means previously described.

In summary, the lymphatic system forms a major part of the immune system, defending the body against infections and harmful bacteria or viruses. However, there are circumstances when the immune system becomes overactive and begins to react to substances that are normally harmless. These substances allergens such as dust or pollen can cause an allergic reaction.

Part 4 of this series on the lymphatic system focuses on allergies and the more severe allergic responses, which could lead to anaphylaxis or life-threatening anaphylactic shock.

Alberts B et al (2015) Molecular Biology of the Cell. Garland Science.

Hauser AE, Hpken UE (2015) B-cell localization and migration in health and disease. In: Alt FW et al (eds). Molecular Biology of B Cells. Academic Press.

Mak TW et al (2014) T-cell development, activation and effector functions. In: Primer to the Immune Response. Academic Cell.

Martnez-Riao A et al (2018) Antigen phagocytosis by B cells is required for a potent humoral response. EMBO Reports; 19: 9, e46016.

Pabst R (2018) The bone marrow is not only a primary lymphoid organ: the critical role for T-lymphocyte migration and housing of long-term memory plasma cells. European Journal of Immunology; 48: 7, 1096-1100.

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The lymphatic system 3: its role in the immune system - Nursing Times

When the number of COVID-19 cases exploded last year, so did the number of products and services promising to bolster your immunity. You couldnt get away from talk of IV vitamin infusions, mushroom extracts, and drinkable immune-boosting shots. You also couldnt get away from Dr. Anthony Fauci, who became a household name after four decades of trying to make sure Americans dont get sick. Ever the straight shooter, he explains that you cant buy a good immune system. If you dont smoke, you only drink in moderation, you get a good nights sleep, have a healthy diet, you exercise, and you do something to reduce stress, thats going to keep your immune system healthy, not any of these dietary supplements and herbs and other things. How he takes his own advice:

I cant alleviate stress during the day, because my day is one big stress period from morning to evening, Dr. Fauci says. So when I get home in the evening, I do a power walk for about three and a half to four miles, and that generally decompresses my stress. The other day, I was walking along Massachusetts Avenue, and son of a gun, I saw a fox run out of somebodys yard into the woods.

When Dr. Fauci mentioned in September that he takes vitamin D and that low levels of that vitamin affect your susceptibility to infection, people heard I take D as you should take D. Not how it goes. If you are deficient in D, then taking vitamin D supplements is important. If you have normal levels, it doesnt make any difference, he says. A doc can check your vitamin D levels via a blood test.

While no specific foods boost your immunity, Dr. Fauci says, an overall balanced diet can help you stay healthy. He aims for balance but sometimes errs in the timing; he can forget to eat dinner unless his wife reminds him. So he gets the day off to a good start with a pretty consistent healthy breakfastusually pomegranate juice and egg whites on an English muffin. Lunch is light; busy nights can mean a takeout salad or salmon burger.

Were gonna give the doctor a bit of a pass on his own advice here, since his sleep took a hit to lower the disease hit for the rest of us. When COVID-19 first spiked, I was getting a ridiculous amount of sleep, like three or four hours a night. Now I get anywhere between five and six, which is not bad, he says, but its not optimal. On the occasion he has a half hour between appointments, Ill lie on my couch in my office and take a power nap.

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Dr. Fauci wears a mask, washes his hands all the time, and compulsively sanitizes them. If youre getting tired of being cautious, you have to realize the seriousness of the situation, he says. Currently, the U.S. has more than 250,000 deaths, and the end is not in sight. Thats enough incentive to be diligent, I think. But he knows its hard. Dont be discouraged. I think you should realize that it will end. Hang in there.

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Here's How Dr. Fauci is Protecting His Immune System During the Pandemic - menshealth.com

This winter, tohave a stronger immune response to the invaders (virus particles that enter your lungs, blood cells, and organs and wreak havoc and cause inflammation) you need to eat a diet high in plant-based foods. Doctors have begun recommending to patients that they switch to a mostly plant-based diet, especially those in the highest risk groups: Overweight, diabetic, over 60, and male. One doctorurges his patientsto eat mostly fruit and vegetables and stay away from inflammation-causing meat, dairy, and processed food, in light of COVID-19.

Your immune system's response is the only thing that can fight COVID. All other therapies are in support of your immune system. If your system is weak or overtaxed with other existing conditions, including obesity or diabetes, it can over-react, creating the "cytokine storm" of inflammation that leads to a cascade of complications that make it harder for your body to self-regulate as it attempts to create antibodies to the virus (essentially molecules that recognize the virus invaders and deploy through the bloodstream to neutralize them)

Immunity is built when your body has to fight off everything fromeveryday aging to infections. And the building blocks of your immunity arehelped by the micronutrients in your food, such as antioxidants and vitamins and minerals, and nothing delivers those better than fruits and vegetables, legumes and nuts and seeds. The flip side is also true, that studies show a diet high in red meat and processed foods can cause inflammation, and in the case of COVID-19, inflammation is the enemy. Patients who do the worst when confronted with this virus are those who are overweight, have chronic inflammation, high blood pressure, or are otherwise immune-compromised.

Here are the foods that are shown to fight inflammation and boost immunity. Eat them now for a stronger immune system, whether you are dealing with COVID-19 or another potential disease that requires your body to be healthier now and later. That includes almost every disease known to man. To be healthier, meaning to build cells that are able to function without bombardment from toxins, oxidization, infection, and internal destruction, plant-based foods are your best bet.

These foods are known to supercharge your immune system, which is your body's defense against infection and illness. It works by recognizing cells that make up your body and will fight off anything unfamiliar. It destroys germs (bacteria and viruses) and parasites. Eat these to bolster your white blood cells and the supporting teams that keep them ready for battle.Healthline compiled the listand The Beet added even more research to bolster the facts.

Your body does not produce vitamin C, which means you need to get it daily to have enough to create healthy collagen (the building blocks for your skin and healing). Also known asascorbic acid, vitamin C is a water-soluble nutrient found inleafy greens and citrus, especially grapefruit, oranges, tangerines, lemons, limes, and clementines. It acts as an antioxidant,protecting cells fromdamage caused by free radicals.

How much do you need a day:The recommended daily amount to shoot for is 65 to 90 milligrams a day, which is the equivalent of one small glass of orange juice or eating a whole grapefruit. Almost all citrus fruits are high in vitamin C. With such a variety to choose from, it's easy to get your fill.

Want even more vitamin C,add red bell peppers to your salad or pasta sauce. One medium-sized red bell pepper contains 152 milligrams of vitamin C, or enough to fulfill your RDA.

Peppers are also a great source of beta carotene, aprecursor of vitamin A (retinol). VitaminAis important for healthy skin, your mucous membranes and your immune system.Beta carotene helps keep your eyes and skin healthy, as well. One cooked pepper has 19 percent of your daily recommended amount of beta carotene.

How much beta carotene do you need a day:You should try to get 75 to 180 microgramsa day which is the equivalent of one medium bell pepper a day. But a red pepper has more than two and a half times your RDA for vitamin C so eat them all winter long.

3. Broccoli, But Eat It Nearly Raw, to get the Most Nutrients Out of It!

Broccolimay be the most super of superfoods on the planet. It's rich in vitamins A and C as well as E. The phytochemicals in it are great for arming and strengthening yourimmune system.

Broccoli is a good source of lutein, a powerful antioxidant, and sulforaphane, another potent antioxidant. Itcontains additional nutrients, including some magnesium, phosphorus, zinc, and iron. The key to keeping its powerful nutrients intact and ready for helping the body's immune response is to cook it as little as possible or even eat it raw.

Lutein is one of 600 known naturally occurring carotenoids and is found in high quantities ingreen leafy veggies such as spinach and kale.

There's another thing you need to know aboutbroccoli,and why it's important to not overcook it. Broccoli contains sulforaphane, a gas that is a killer to a bug in the gardenand in the body.Sulforaphane is a sulfur-rich compound found in several cruciferous vegetableslike bok choy, cabbage, and kale, butbroccoli delivers the most. When a bug bites into the stalk, leaf, or flowering bud of the plant it releases this sulfuric gas that kills the invaders, thereby protecting the plant. This is the same agent that gives broccoli that sulfuric smell when you cook it, so don't overcook it since you'd rather all of that end up in your body than in the kitchen air. Cook it too much and the gas escapes into your kitchen, so if you want to keep it in the plant, and delivered it to your body, lightly steam the green and add it to your meal barely cooked through.

How much lutein should you eat in a day: There is no RDA for lutein, but experts say get at least 6 milligrams.

Garlics immune-boosting propertiesare tied to itssulfur-containing compounds, such as allicin. Allicin is thought to improve your immune cells' ability to fight off colds and flu, and viruses of all kinds. (Smelling more garlic on the subway? It could be smart coronavirus management.) Garlic also has anti-microbial and anti-viral properties thought to fight off infections.

5. Ginger is a Power Player for Immunity and Digestion

Ginger is another ingredient that has super properties when it comes to fighting off illness. It has been shown todecrease inflammation, which can helpif you get swollen glands or a sore throat or anyinflammatoryailment.

Gingerol,the main bioactive compound in ginger, is a relative of capsaicin, can be used in sweet or spicy dishes. It has been found to alleviate pain and fight nausea, which is the reason ginger ale was given for upset stomachs, back when it contained actual ginger. Now few store-bought formulations do. Make your own ginger tea. Gingerol is responsible for much of its medicinal properties. It has powerful anti-inflammatory and antioxidantbenefits.

How muchshould you eat a day: Most recommendations land on 34 grams of ginger extract a day, or up to four cups of ginger tea, but no more than 1 gram a day if you are pregnant. Some studies have linked high dosages to an increased risk of miscarriage.

Spinachis not only packed with vitamin C but also antioxidants and beta carotene, both of which give your immune system the healthy boost it needs to fight off invaders.

Don't overcook your spinach, since the more it's cooked the less active the antioxidants will be. If you eat it raw or lightly steamed you'll keep more of the nutrients intact.

How much should you eat a day:Aim for 1 cup freshspinachor 1/2 cup cooked perday, but this isthe right moment to try the raw or slightly wilted approach. Order warm or wilted spinach salad when you go out, or make it yourself with olive oil, pine nuts, and vegan parm.

7. Almonds for the Win, Pop Them Like Candy

Vitamin E in almonds will help ward off colds and flu and is key to your immune system humming along. Its afat-solublemolecule, meaning it requires the presence of fat to be absorbed, so nuts arethe perfect package for E to make it into your system.

How much should you eat in a day:A half-cup serving, or46 whole, shelled almonds, providesalmost 100 percent of your RDA of vitamin E. Almonds are great for you but they don't come with a "free" pass, since 1/4 cup is a serving and has 162 calories, so double that for your RDA and you're eating about 325 calories. Throw them into smoothies instead.

If you ever feel healthier for eating curry, it is probably because of the Tumeric, which is an ingredient that gives it its burnt orange color. But this highly pigmented spice is known for its anti-inflammatory qualities. The ingredientcurcumin hasbeen found to decrease muscle soreness after a hard workout. How it helps immunity? decrease exercise-induced muscle damage.

Tumeric bolsters theimmunesystem by stimulating antibody formation and people with auto-immune diseases are told by their doctors to take 500 mg of curcumin daily to reduce inflammation and stave off soreness.

How much should you eat in a day: Try adding extra Tumeric to your diet during periods of stress or during flu season. Or take500-2,000 mg ofcurcuminto help fight inflammation and power up your immune system.

9. Green Tea by the Gallon, Skip the Coffee andSipthis Instead

Whether you prefer green tea or black tea, you will benefit from the compounds calledflavonoids, powerful antioxidants.Green tea has highlevels of EGCG, (epigallocatechin gallate) another hard-working antioxidant.

EGCG is known to boost immune function, and originally all tea leaves contain this anti-oxidant, but when black tea is fermented it deactivates mostof the EGCG. Green tea is steamed so the EGCG isstill active when you drink it.

Green tea also containsL-theanine, an anti-oxidant which appears to help in the production of T-cells in your body, the killerL-theanine may aid in the production of germ-fighting compounds in your T-cells.

How much green tea should you drink in a day: The optimal amount isthree to five cups in a day,but most people won't get to that level. Any amount is better than nothing. Swap out ausual beverage dailyfor green tea could improve your health.

10. Papaya, The Tropical Healer to Keep You Vacation-Healthy All Year Round

Papaya deliversover twice yourrecommended daily amount of vitamin C inone fruit -- though you're likely to eat a few slices on a salad or in a smoothie.It also contains an enzyme called papain that has anti-inflammatory effects -- and inflammation is one factor in most illnesses, so avoiding it can help your body fight off bacterial infections like sinusitis.

Papayas containpotassium, vitamin B, and folate, which is a powerful cell rebuilder. Exactly how folic acid works to build immunity is linked to its role inprotein synthesis, and researchers think that any mechanism in which cells proliferate can be affected (which is why it's critical for pregnant women). People who are folate-deficienthave compromised immune systems.

How much folate should youeat a day: Whether you are pregnant or not, folate (vitamin B9) is a great vitamin to keep your cells healthy and strong. The recommendation is 400 micrograms a day, or get it from legumes, spinach, papayas, and avocados.

When you think of anti-oxidants, you should think of fruits that grow in the sun, since their vitamin pack comes from having to fight off the oxidation of the strong rays that beat down on them in the tropics. Kiwis are a great example. They are full of folate, vitamin K, vitamin C, and potassium.

These vitamins in combination work in the body to build healthy cells, fight infection and keep your immune system humming along. Vitamin K deficiency is rare but when people don't have enough they suffer from weak bones and compromised immune systems. The inflammation system in the body is also dependent on vitamin K, especially your killerT cells that mobilize and fight cancer and other diseases.

How much should you eat in a day: Vitamin K is one of the unsung heroes of the body. Women shouldget 90 micrograms a day, and menshould have120 micrograms.

12. Sunflower seeds to sprinkle on salads or eat by themselves

Most seeds are chock-o-block with nutrients since they give the plant its healthy start. But sunflower seeds are especially healthy since they provide phosphorus, magnesium and vitamin B-6 as well as vitamin E.Your immune system needs vitamin E to function at full throttle.You can also get vitamin E fromavocados and spinach and broccoli.

How much should you eat in a day:Anywhere from1 ounce (30 grams) per dayto a healthy handful is considered healthy, but because they are high in sodium you might want to refrain from eating the entire bag. The raw seeds have 204 calories per quarter cup.

13. Miso, Soup or Paste to Add to Your Soups and Salad Dressings

You've had miso soup at your favorite Japanese restaurant and perhaps even thought: "This tastes incredibly healthy! If a bit salty." Both thoughts are true. Miso is a fermented paste that adds a salty umami flavor to many Japanese dishes and soup. Most miso is made in Japan, where the ingredient has been used since the eighth century.

Misoneeds no preparation andadds a touch of saltiness to soups,marinades, and dressings. Some people credit miso as a factor in Japanese longevity. Japan has more centenarians per capita of the population than anywhere else in the world and Japan has one of the lowest rates of obesity.

The nutrients in miso -- which is a soybean paste that has been fermented with salt and a koji starter -- boostsimmune system functionby delivering healthy probiotics tothe gut, making yourmicrobiome healthier. How doesMiso benefit your immune system?It is a "sirt" food, which are foods that contain high levels of sirtuins or proteins that regulate cells and activate metabolism. A diet high in sirts is believed to lead to weight loss, increased wellness, and longevity.

How much should you eat in a day:Researchersbelieve that consuming one bowl of miso soup per day, as is the tradition in Japan,lowers the risks of breast cancer. Other than its high sodium content there is no reason to stay away from miso with all its varied health benefits. We say cheers to that.

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13 Foods to Boost Your Immune System and Fight Sickness - The Beet

Against the backdrop of the ongoing pandemic, its more important than ever to keep tabs on our health, diet and lifestyle. Supporting and building our immune systems by tweaking our diets and ensuring we get a good nights sleep can help them stay strong whatever your current health is like, the best defence weapon against any illness Covid-19 included is bolstering your immune function.

We can start by considering what we eat and drink everyday. Here are my four golden rules to try now.

Cut out or limit processed packaged foods, as well as hydrogenated fats and vegetable oils; takeaways; fast food; e-numbers and additives; sugary treats and baked goods; poor quality protein and deli meats; and cigarettes and alcohol. They all upset our immune system.

Opt for an abundance of fresh fruit and veg; clean proteins like organic meats; legumes; free-range eggs; extra virgin olive oil; nuts and seeds; and complex whole carbs like root veggies and gluten-free wholegrains. When you focus on foods like these, your diet will naturally be full of nutrients, vitamins and minerals that have the ability to support a strong immune system.

As well as ingesting liposomal vitamin C to help the immune system protect against viral infections more efficiently, I also recommend taking a good quality zinc supplement (it activates enzymes that break down proteins in viruses and bacteria so they are less able to spread), vitamin D, and a good quality probiotic, like Symprove, to help keep the gut in check.

A healthy gut microbiome is the foundation for your overall wellness, as it triggers your bodys immune response when it detects invaders. How many of us even consider it? As well as taking a good quality probiotic and eating a balanced diet as mentioned above, its important to get seven to nine hours of sleep each night, exercise regularly, manage stress and limit your alcohol intake. Plus, drinking adequate fluid, whether thats water, broths or herbal teas, is key.

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A Nutritionists Guide To Keeping Your Immune System Strong This Winter - British Vogue