tag:theconversation.com,2011:/es/topics/t-cell-77955/articlesT-cell – The Conversation2020-10-02T14:02:45Ztag:theconversation.com,2011:article/1473912020-10-02T14:02:45Z2020-10-02T14:02:45ZOlder people like President Trump are at more risk from COVID-19 because of how the immune system ages<figure><img src="https://images.theconversation.com/files/361389/original/file-20201002-22-1i0nzfk.jpg?ixlib=rb-1.1.0&rect=391%2C270%2C4173%2C2891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Masking up is one way to cut down on risk of COVID-19 infection.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/president-donald-trump-wears-a-face-mask-while-he-pays-his-news-photo/1228685397">Alex Brandon/Getty Images News via Getty Images</a></span></figcaption></figure><p>President Donald Trump’s announcement that <a href="https://twitter.com/realDonaldTrump/status/1311892190680014849">he’s tested positive for COVID-19</a> is especially concerning because of his age. At 74 years old, Trump is solidly within an age group that’s been hit hard during the coronavirus pandemic.</p>
<p>People of all ages can get sick from SARS-CoV-2, the virus that causes COVID-19. But the severity of the illness tends to worsen the older the patient is. Through the end of September, <a href="https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#AgeAndSex">79% of COVID-19 deaths</a> in the United States had been in patients over 65. These statistics are <a href="https://doi.org/10.3855/jidc.12600">broadly similar</a> <a href="https://ourworldindata.org/coronavirus">in countries around the world</a>.</p>
<p>What is it that puts older people at increased risk from viruses like SARS-CoV-2? Scientists think it’s primarily due to changes in the human immune system as we age.</p>
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<h2>Your body’s tools to fight off virus infections</h2>
<p>As you go about your life, your body is constantly bombarded by pathogens – the bacteria, fungi and viruses that can make you sick. A human body is a great place for these organisms to grow and thrive, providing a nice warm environment with plenty of nutrients.</p>
<p>That’s where your immune system comes in. It’s your body’s defense system against these kinds of invaders. Before you’re even born, your body starts producing specialized B-cells and T-cells – types of white blood cells that can recognize pathogens and help block their growth.</p>
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<a href="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">An artist’s rendering of the white blood cells that help recognize and fight off invaders.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/lymphocytes-illustration-royalty-free-illustration/685027719">Kateryna Kon/Science Photo Library via Getty Images</a></span>
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<p>During an infection, your B-cells can proliferate and produce antibodies that grab onto pathogens and block their ability to spread within your body. T-cells work by recognizing infected cells and killing them. Together they make up what scientists call your “adaptive” immune system.</p>
<p>Maybe your physician has checked your white blood cell levels. That’s a measurement of whether you have more B-cells and T-cells in your blood than usual, presumably because they’re fighting infection.</p>
<p>When you’re very young, you don’t have a lot of these B- or T-cells. It can be a challenge for your body to control infection because it’s simply not used to the job. As you mature, your adaptive immune system learns to recognize pathogens and handle these constant invasions, allowing you to fight off infection quickly and effectively.</p>
<p>While white blood cells are powerful people-protectors, they’re not enough on their own. Luckily, your immune system has another layer, what’s called your <a href="https://doi.org/10.1159/000453397">“innate” immune response</a>. Every cell has its own little immune system that allows it to directly respond to pathogens quicker than it takes to mobilize the adaptive response.</p>
<p>The innate immune response is tuned to pounce on types of molecules that are commonly found on bacteria and viruses but not in human cells. When a cell detects these invader molecules, it triggers production of an antiviral interferon protein. Interferon triggers the infected cell to die, limiting infection. </p>
<p>Another type of innate immune cell, called a monocyte, acts as a sort of cellular bouncer, getting rid of any infected cells it finds and signaling the adaptive immune response to shift into gear.</p>
<p>The innate and adaptive immune systems can act together as a fine-tuned machine to detect and clear out pathogens.</p>
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<h2>Older immune systems are weaker</h2>
<p>When a pathogen invades, the difference between illness and health is a race between how fast the pathogen can spread within you and how fast your immune response can react without causing too much collateral damage.</p>
<p>As people age, their innate and adaptive immune responses change, shifting this balance.</p>
<p><a href="https://doi.org/10.1016/j.humimm.2009.07.005">Monocytes from older individuals</a> <a href="https://doi.org/10.1093/infdis/jir048">produce less interferon</a> in response to viral infections. They have a harder time killing infected cells and signaling the adaptive immune response to get going.</p>
<p>Low-grade chronic inflammation in individuals that commonly occurs during aging can also <a href="https://doi.org/10.1111/j.1749-6632.2000.tb06651.x">dull the ability of the innate and adaptive immune responses</a> to react to pathogens. It’s similar to becoming used to an annoying sound over time.</p>
<p>As you age, the reduced “attention span” of your innate and adaptive immune responses make it harder for the body to respond to viral infection, giving the virus the upper hand. Viruses can take advantage of your immune system’s slow start and quickly overwhelm you, resulting in serious disease and death.</p>
<h2>Social distancing is vital</h2>
<p>Everyone, no matter their age, needs to protect themselves from infection, not just to keep themselves healthy but also to help protect the most vulnerable. Given the difficulty older individuals have in controlling viral infection, the best option is for these individuals to avoid becoming infected by viruses in the first place.</p>
<p>This is where washing hands, avoiding touching your face, self-isolation and <a href="https://theconversation.com/social-distancing-what-it-is-and-why-its-the-best-tool-we-have-to-fight-the-coronavirus-133581">social distancing</a> all become important, <a href="https://www.cdc.gov/coronavirus/2019-ncov/prepare/prevention.html">especially for COVID-19</a>.</p>
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<span class="caption">The mist ejected by a sneeze can launch viruses airborne, so other people can inhale them.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=11161">James Gathany</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>COVID-19 is caused by a respiratory virus, which can spread via tiny virus-containing droplets. Larger droplets fall to the ground quickly; very small droplets dry up. Mid-range droplets are of most concern because they can <a href="https://www.medscape.com/viewarticle/741245_3">float in the air for a few feet</a> before drying. These droplets can be inhaled into the lungs.</p>
<p>Keeping at least 6 feet away from other people helps significantly reduce your chance of being <a href="https://doi.org/10.1186/s12879-019-3707-y">infected by these aerosol droplets</a>. But there’s still the <a href="https://theconversation.com/viruses-live-on-doorknobs-and-phones-and-can-get-you-sick-smart-cleaning-and-good-habits-can-help-protect-you-133054">possibility for virus to contaminate surfaces</a> that infected people have touched or coughed on. Therefore, the best way to protect vulnerable older and immunocompromised people is to stay away from them until there is no longer a risk. By stopping the spread of SARS-CoV-2 throughout the whole population, we help protect those who have a harder time fighting infection.</p>
<p><em>This article draws on material from <a href="https://theconversation.com/older-people-are-at-more-risk-from-covid-19-because-of-how-the-immune-system-ages-133899">an article originally published</a> on March 19, 2020.</em></p><img src="https://counter.theconversation.com/content/147391/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Geiss receives funding from the National Institutes of Health.</span></em></p>Older coronavirus patients face grimmer outlooks. A virologist explains the aging-related changes in how immune systems work that are to blame.Brian Geiss, Associate Professor of Microbiology, Immunology & Pathology, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1433232020-08-26T12:22:26Z2020-08-26T12:22:26ZDeclining antibodies and immunity to COVID-19 – why the worry?<figure><img src="https://images.theconversation.com/files/350678/original/file-20200731-25-14azhjx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6540%2C4442&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An artist's impression of antibodies (red and blue) responding to an infection with the new coronavirus SARS-CoV-2 (purple). </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/antibodies-responding-to-covid-19-royalty-free-illustration/1227513276?adppopup=true">KTSDESIGN/SCIENCE PHOTO LIBRARY / Getty Images</a></span></figcaption></figure><p>Most people are aware that testing for antibodies in a person’s blood can show if someone has had a specific disease, such as COVID-19. Those antibodies provide protection from getting the disease again.</p>
<p>But in a <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2025179">paper published in the New England Journal of Medicine</a>, researchers found that antibody levels decline in individuals who have recovered from COVID-19, dropping by half every 36 days. Does that mean people who have recovered from COVID-19 have lost their immunity? </p>
<p><a href="https://scholar.google.com/citations?user=VMa6rFgAAAAJ&hl=en">I am a geneticist</a> interested in innate immune response – the part of the immune system that we have at birth – and how the innate immune cells “educate” antibody-producing cells about a pathogen and how to identify and destroy it. As I’ll explain, antibodies are important for immunity, but they aren’t the only factor that counts.</p>
<h2>Two arms of the immune system</h2>
<p>The immune system is made up of two parts: innate immunity and adaptive – or acquired – immunity. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/books/NBK279396/">The innate immune system</a>, which includes white blood cells called dendritic cells, monocytes and neutrophils, is present at birth and responds instantly to invaders. This group of white blood cells bombard pathogens with destructive chemicals and swallow and destroy viruses and bacteria. The innate immune system provides an instantaneous reaction to a pathogen. The problem is that it’s a blunt instrument – it responds the same way to all perceived threats. </p>
<p>The adaptive immune system, which is made up of B cells and T cells, must learn about a pathogen and its characteristics from the innate immune cells. This system takes longer to kick in, but the up side is that it is very specific and in many cases lasts a lifetime.</p>
<h2>The immune system’s memory</h2>
<p>The history of pathogen exposure is carried in so-called memory T cells and memory B cells. When an infection is defeated and gone, these cells reside in the peripheral tissues of the body such as lymph nodes or spleen and serve as a memory of the disease-causing virus. This immunological memory is responsible for the host defense and kicks into action in case of the second wave or attack of the pathogen. </p>
<p>It is normal for <a href="https://www.scientificamerican.com/article/concerns-about-waning-covid-19-immunity-are-likely-overblown/">antibody levels to decline</a> after a person has recovered from a disease. But the New England Journal of Medicine paper <a href="https://www.cidrap.umn.edu/news-perspective/2020/07/study-covid-19-antibodies-decay-quickly-after-mild-illness">raised concerns</a> because it suggests that we are losing our immunological memory – which is as bad as losing a real memory.</p>
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<a href="https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=472&fit=crop&dpr=1 600w, https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=472&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=472&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=593&fit=crop&dpr=1 754w, https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=593&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/351399/original/file-20200805-237-1wd13k0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=593&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Basophils, Neurophils, Eosinophils and Monocytes (left) make up the innate immune system. B cells and T cells are part of the adaptive immune system.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/vector-types-of-blood-cells-erythrocytes-royalty-free-illustration/1216602031?adppopup=true">Vitalii Dumma / Getty Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>What role do T cells play in immunity?</h2>
<p>B cells and antibodies are only part of the immune response. T cells help B cells produce antibodies – which are proteins that can bind to a specific pathogen and destroy it.</p>
<p>The way this happens is that first the B cells swallow the virus and start producing antibodies. </p>
<p>T cells cannot swallow the virus. But a type of white blood cell called an antigen-presenting cell can. After it does, it “shows” different parts of the virus to the T cells. The T cells then learn about the virus which they can now seek and destroy. </p>
<p>T cells also stick to the B cells and send them the activation signals that help B cells ramp up antibody production.</p>
<h2>If antibodies decline, what does this mean for COVID-19 immunity?</h2>
<p>It suggests that when there are fewer antibodies in the blood, there is a greater chance that a number of individual virus particles, called virions, will survive and escape destruction. Therefore, the remaining virions will continue to proliferate and cause disease.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<h2>What do declining antibody levels mean for establishing herd immunity?</h2>
<p>Herd immunity refers to a population and occurs when a sufficiently high number of people within a community are immune to the virus and incapable of transmitting it. That provides protection for those who are still vulnerable. For example, if 60% of people are protected against COVID – because they have survived the infection and carry antibodies – it might protect (via less frequent interactions) the remaining 40% from getting sick. </p>
<p>But the results in the New England Journal of Medicine suggest that people with lower levels of antibody may still have the virus and may not have symptoms of the disease. </p>
<p>That means that if these people with low antibody levels hang around healthy, uninfected people, they present a danger to them because they can transmit the virus. </p>
<h2>When antibody levels fall, does immunity disappear?</h2>
<p>In general, the answer is no. If the virus attempts to cause a second infection, the memory B and T cells are able to recognize it, multiply million of times and defend the body against the virus, preventing it from triggering another full-blown infection. </p>
<p>The protection provided by memory T and B cells is the reason that vaccine-based protection works.</p>
<p>However, there are exceptions. A lifelong vaccine against the flu does not work because flu’s genetic code changes rapidly, altering the appearance of the flu, and therefore requires a new vaccine every season. </p>
<p>But with SARS-CoV-2, the problem as I see it, seems to be that those <a href="https://doi.org/10.1038/s41467-020-17292-4">memory T cells </a><a href="https://doi.org/10.1038/s41591-020-1038-6">and B cells</a> seem to be wiped out. </p>
<p>Antibodies are proteins and last for only between three and four weeks in the blood circulation. To keep antibody levels high, B cells need to replenish them with a fresh supply. But in COVID-19, the declining antibody levels suggest that the cells that produce these antibodies are not present in sufficient numbers, which would explain the drop in antibody levels. Studies of how long immunity from COVID-19 last may shed more light, but for now we do not know the reason why.</p><img src="https://counter.theconversation.com/content/143323/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alexander (Sasha) Poltorak does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>If antibody levels drop dramatically after an infection, what does that mean for immunity? An expert explains how B and T cells contribute to immunity and why antibodies don’t tell the full story.Alexander (Sasha) Poltorak, Professor of Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1449912020-08-25T12:24:42Z2020-08-25T12:24:42ZA man was reinfected with coronavirus after recovery – what does this mean for immunity?<figure><img src="https://images.theconversation.com/files/354454/original/file-20200824-22-kbunl3.jpg?ixlib=rb-1.1.0&rect=14%2C36%2C4808%2C3176&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Is it possible to get COVID-19 twice?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/man-wearing-a-face-mask-as-a-precautionary-measure-against-news-photo/1228166500?adppopup=true">May James/AFP via Getty Images</a></span></figcaption></figure><p>A 33-year old man was found to have <a href="https://www.statnews.com/2020/08/24/first-covid-19-reinfection-documented-in-hong-kong-researchers-say/">a second SARS-CoV-2 infection</a> some four-and-a-half months after he was diagnosed with his first, from which he recovered. The man, who showed no symptoms, was diagnosed when he returned to Hong Kong after a trip to Spain. </p>
<p><a href="https://scholar.google.com/citations?user=ubfhdQwAAAAJ&hl=en">I am a virologist</a> with expertise in coronaviruses and enteroviruses, and I’ve been curious about reinfections since the beginning of the pandemic. Because people infected with SARS-CoV-2 can often test positive for the virus for weeks to months, likely due to the sensitivity of the test and <a href="https://doi.org/10.1002/jmv.25952">leftover RNA fragments</a>, the only way to really answer the question of reinfection is by sequencing the viral genome at the time of each infection and looking for differences in the genetic code. </p>
<p>There is no published peer-review report on this man – only a press release from the University of Hong Kong – although reports say the work will be published in the journal <a href="https://academic.oup.com/cid">Clinical Infectious Diseases</a>. Here I address some questions raised by the current news reports. </p>
<h2>Why wasn’t the man immune to reinfection?</h2>
<p>Immunity to endemic coronaviruses – those that cause symptoms of the common cold – <a href="http://doi.org/10.1136/adc.58.7.500">is relatively short-lived</a>, <a href="http://doi.org/10.1017/s0950268800048019">with reinfections occurring</a> even within the same season. So it isn’t completely surprising that reinfection with SARS-CoV-2, the virus that causes COVID-19, might be possible.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/books/NBK279396/">Immunity is complex and involves multiple mechanisms</a> in the body. That includes the generation of antibodies – through what’s known as the adaptive immune response – and through the actions of T-cells, which can help to educate the immune system and to specifically eliminate virus-infected cells. However, researchers around the world are still learning about immunity to this virus and so can’t say for sure, based on this one case, whether reinfection will be a cause for broad concern.</p>
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<h2>How different is the second strain that infected the Hong Kong man?</h2>
<p>“Strain” has a particular definition when referring to viruses. Often a different “strain” is a virus that behaves differently in some way. The coronavirus that infected this man in Europe is likely not a new strain. </p>
<p>A <a href="https://www.statnews.com/2020/08/24/first-covid-19-reinfection-documented-in-hong-kong-researchers-say/">STAT News article</a> reports that the <a href="https://nextstrain.org/ncov/global">genetic make up of the sequenced virus</a> from the patient’s second infection had 24 nucleotides – building blocks of the virus’s RNA genome – that differed from the <a href="https://www.ncbi.nlm.nih.gov/nuccore/1798174254">SARS-CoV-2 isolate</a> that infected him the first time. </p>
<p>SARS-CoV-2 has a genome that is made up of about 30,000 nucleotides, so the virus from the man’s second infection was roughly 0.08% different than the original in genome sequence. That shows that the virus that caused the second infection was new; not a recurrence of the first virus. </p>
<h2>The man was asymptomatic – what does that mean?</h2>
<p>The man wasn’t suffering any of the hallmark COVID-19 symptoms which might mean he had some degree of protective immunity to the second infection because he didn’t seem sick. But this is difficult to prove.</p>
<p>I see three possible explanations. The first is that the immunity he gained from the first infection protected him and allowed for a mild second infection. Another possibility is that the infection was mild because he was presymptomatic, and went on to develop symptoms in the coming days. Finally, sometimes infections with SARS-CoV-2 are asymptomatic – at the moment it is difficult to determine whether this was due to the differences in the virus or in the host.</p>
<h2>What can we say about reinfection based on this one case?</h2>
<p>Only that it seems to be possible after enough time has elapsed. We do not know how likely or often it is to occur.</p>
<h2>Should people who have recovered from COVID-19 still wear a mask?</h2>
<p>As we are still learning about how humans develop immunity to SARS-CoV-2 after infection, my recommendation is for continued masking, hand hygiene and distancing practices, even after recovery from COVID-19, to protect against the potential for reinfection.</p><img src="https://counter.theconversation.com/content/144991/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Culler Freeman is funded by the Pediatric Infectious Diseases Society St. Jude Children's Research Hospital Fellowship in Basic and Translational Research. </span></em></p>Reports describe a Hong Kong man who was reinfected with the coronavirus after returning from Europe. Does that mean he wasn’t immune after the first infection?Megan Culler Freeman, Pediatric Infectious Diseases Fellow, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1338992020-03-19T12:06:52Z2020-03-19T12:06:52ZOlder people are at more risk from COVID-19 because of how the immune system ages<figure><img src="https://images.theconversation.com/files/321466/original/file-20200319-126270-1h2b5un.jpg?ixlib=rb-1.1.0&rect=207%2C39%2C3367%2C2441&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A nursing home resident who tested positive for the virus visits through the window with her daughter.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-US/ad2fd7eca51e46b5a390af76f9d8aa7e/2/0">AP Photo/Ted S. Warren</a></span></figcaption></figure><p><em>An updated version of this article was published on Oct. 2, 2020. <a href="https://theconversation.com/older-people-like-president-trump-are-at-more-risk-from-covid-19-because-of-how-the-immune-system-ages-147391">Read it here</a>.</em></p>
<p>The rapidly spreading coronavirus pandemic is taking a particularly harsh toll on older people.</p>
<p><a href="https://doi.org/10.3855/jidc.12600">Data from the initial outbreak in China and then Italy</a> show that infected people under the age of 60 are at low – but not no – risk of dying from COVID-19. More recent data from the U.S. suggest that a <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm?s_cid=mm6912e2_w">higher rate of people in their 30s and 40s</a> have experienced severe illness and even death than previously thought. Curiously, <a href="https://www.washingtonpost.com/health/2020/03/17/coronavirus-looks-different-kids-than-adults/">young children</a> do not appear to be at increased risk of serious COVID-19 complications, in contrast to what happens with other viruses, <a href="https://www.cdc.gov/flu/highrisk/children.htm">like the seasonal flu</a>. </p>
<p>However, the statistics get <a href="https://doi.org/10.3855/jidc.12600">grimmer as the patients get older</a>. Whereas people in their 60s have a 0.4% chance of dying, people in their 70s have a 1.3% chance of dying, and people over 80 have a 3.6% chance of dying. While this may not sound like a high chance of death, during the current outbreak in Italy, <a href="https://doi.org/10.1016/S0140-6736(20)30627-9">83% of those who succumbed to COVID-19</a> infection were over the age of 60.</p>
<p>The new coronavirus SARS-CoV-2, which causes COVID-19, is therefore a <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm">very serious pathogen for people over 60</a>. As it continues to spread, this older age group will continue to be at risk for serious disease and death.</p>
<p>What is it that puts older people at increased risk from viruses like this? It’s primarily thought to be due to changes in the human immune system as we age.</p>
<h2>Your body’s tools to fight off virus infections</h2>
<p>As you go about your life, your body is constantly bombarded by pathogens – the bacteria, fungi and viruses that can make you sick. A human body is a great place for these organisms to grow and thrive, providing a nice warm environment with plenty of nutrients.</p>
<p>That’s where your immune system comes in. It’s your body’s defense system against these kinds of invaders. Before you’re even born, your body starts producing specialized B-cells and T-cells – types of white blood cells that can recognize pathogens and help block their growth.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321468/original/file-20200319-126300-18zc0vh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An artist’s rendering of the white blood cells that help recognize and fight off invaders.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/lymphocytes-illustration-royalty-free-illustration/685027719">KATERYNA KON/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>During an infection, your B-cells can proliferate and produce antibodies that grab onto pathogens and block their ability to spread within your body. T-cells work by recognizing infected cells and killing them. Together they make up what scientists call your “adaptive” immune system.</p>
<p>Maybe your physician has checked your white blood cell levels. That’s a measurement of whether you have more B-cells and T-cells in your blood than usual, presumably because they’re fighting infection.</p>
<p>When you’re very young, you don’t have a lot of these B- or T-cells. It can be a challenge for your body to control infection because it’s simply not used to the job. As you mature, your adaptive immune system learns to recognize pathogens and handle these constant invasions, allowing you to fight off infection quickly and effectively.</p>
<p>While white blood cells are powerful people protectors, they’re not enough on their own. Luckily, your immune system has another layer, what’s called your <a href="https://doi.org/10.1159/000453397">“innate” immune response</a>. Every cell has its own little immune system that allows it to directly respond to pathogens quicker than it takes to mobilize the adaptive response.</p>
<p>The innate immune response is tuned to pounce on types of molecules that are commonly found on bacteria and viruses but not in human cells. When a cell detects these invader molecules, it triggers production of an antiviral interferon protein. Interferon triggers the infected cell to die, limiting infection. </p>
<p>Another type of innate immune cell, called a monocyte, acts as a sort of cellular bouncer, getting rid of any infected cells it finds and signaling the adaptive immune response to shift into gear.</p>
<p>The innate and adaptive immune systems can act together as a fine-tuned machine to detect and clear out pathogens.</p>
<h2>Older immune systems are weaker</h2>
<p>When a pathogen invades, the difference between illness and health is a race between how fast the pathogen can spread within you and how fast your immune response can react without causing too much collateral damage.</p>
<p>As people age, their innate and adaptive immune responses change, shifting this balance.</p>
<p><a href="https://doi.org/10.1016/j.humimm.2009.07.005">Monocytes from older individuals</a> <a href="https://doi.org/10.1093/infdis/jir048">produce less interferon</a> in response to viral infection. They have a harder time killing infected cells and signaling the adaptive immune response to get going.</p>
<p>Low-grade chronic inflammation in individuals that commonly occurs during aging can also <a href="https://doi.org/10.1111/j.1749-6632.2000.tb06651.x">dull the ability of the innate and adaptive immune responses</a> to react to pathogens. It’s similar to becoming used to an annoying sound over time.</p>
<p>As you age, the reduced “attention span” of your innate and adaptive immune responses make it harder for the body to respond to viral infection, giving the virus the upper hand. Viruses can take advantage of your immune system’s slow start and quickly overwhelm you, resulting in serious disease and death.</p>
<h2>Social distancing is vital</h2>
<p>Everyone, no matter their age, needs to protect themselves from infection, not just to keep themselves healthy but also to help protect the most vulnerable. Given the difficulty older individuals have in controlling viral infection, the best option is for these individuals to avoid becoming infected by viruses in the first place.</p>
<p>This is where washing hands, avoiding touching your face, self-isolation and <a href="https://theconversation.com/social-distancing-what-it-is-and-why-its-the-best-tool-we-have-to-fight-the-coronavirus-133581">social distancing</a> all become important, <a href="https://www.cdc.gov/coronavirus/2019-ncov/prepare/prevention.html">especially for COVID-19</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=378&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=378&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=378&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=475&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=475&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321445/original/file-20200318-1905-pndn5q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=475&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The mist ejected by a sneeze can launch viruses airborne, so other people can inhale them.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=11161">James Gathany</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>COVID-19 is caused by a respiratory virus, which can spread via tiny virus-containing droplets. Larger droplets fall to the ground quickly; very small droplets dry up. Mid-range droplets are of most concern because they can <a href="https://www.medscape.com/viewarticle/741245_3">float in the air for a few feet</a> before drying. These droplets can be inhaled into the lungs.</p>
<p>Keeping at least 6 feet away from other people helps significantly reduce your chance of being <a href="https://doi.org/10.1186/s12879-019-3707-y">infected by these aerosol droplets</a>. But there’s still the <a href="https://theconversation.com/viruses-live-on-doorknobs-and-phones-and-can-get-you-sick-smart-cleaning-and-good-habits-can-help-protect-you-133054">possibility for virus to contaminate surfaces</a> that infected people have touched or coughed on. Therefore, the best way to protect vulnerable older and immunocompromised people is to stay away from them until there is no longer a risk. By stopping the spread of SARS-CoV-2 throughout the whole population, we help protect those who have a harder time fighting infection.</p>
<p><em>This article has been updated to clarify that people of all ages are at risk of coming down with COVID-19.</em></p><img src="https://counter.theconversation.com/content/133899/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Geiss receives funding from the National Institutes of Health. </span></em></p>Different demographics are more or less vulnerable to serious complications from the coronavirus. A virologist explains the aging-related changes in how immune systems work that are to blame.Brian Geiss, Associate Professor of Microbiology, Immunology & Pathology, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1268062019-11-18T14:04:07Z2019-11-18T14:04:07ZHow gene-edited white blood cells are helping fight cancer<figure><img src="https://images.theconversation.com/files/301829/original/file-20191114-26211-1bih0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists are using gene editing to make better cancer treatments.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/crispr-gene-edit-concept-genetic-engineering-1342323245?src=62f4801b-c214-4ef0-a90c-fdd9058cd01e-1-27">Lightspring/Shutterstock.com</a></span></figcaption></figure><p>For the first time in the United States, a gene editing tool has been used to treat advanced cancer in three patients and showed promising <a href="https://ash.confex.com/ash/2019/webprogram/Paper122374.html">early results</a> in a pilot phase 1 <a href="https://clinicaltrials.gov/ct2/show/NCT03399448?term=parker&cond=CRISPR&draw=2&rank=1">clinical trial</a>. So far the treatment appears safe, and more results are expected soon.</p>
<p>To develop a safer and more effective treatment for cancer patients, scientists from the <a href="https://home.www.upenn.edu/">University of Pennsylvania</a>, <a href="https://www.parkerici.org/">the Parker Institute for Cancer Immunotherapy</a> in San Francisco and <a href="https://www.tmunity.com/">Tmunity Therapeutics</a>, a biotech company in Philadelphia, developed an advanced version of immunotherapy. In this treatment, a patient’s own immune cells are removed from the body, trained to recognize specific cancer cells and then finally injected back into the patient where they multiply and destroy them. </p>
<p>Unlike chemotherapy or radiation therapy, which directly kills cancer cells, immunotherapy activates the body’s own immune system to do the work. This team used a gene editing tool called CRISPR to alter immune cells, turning them into trained soldiers to locate and kill cancer cells. By using this technique, the team hoped to develop a more effective form of immunotherapy with minimal side effects.</p>
<p><a href="https://scholar.google.com/citations?user=qtpo58sAAAAJ&hl=en">I am trained as a pharmaceutical scientist</a> and a biomolecular engineer, and I was particularly interested to learn about this new therapy because <a href="https://www.che.ufl.edu/jain/">my lab</a> focuses on editing the gene editors. In particular, I am trying to develop even better CRISPR-based gene editors for the diagnosis and treatment of cancer and other disorders. We combine chemistry, biology and nanotechnology to engineer, control and deliver gene editing tools more efficiently and precisely. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=499&fit=crop&dpr=1 600w, https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=499&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=499&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=627&fit=crop&dpr=1 754w, https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=627&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/301833/original/file-20191114-26202-e4lhqm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=627&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A pseudo-colored scanning electron micrograph shows two T-cells (red) attacking a cancer cell (white). Researchers are creating more powerful cancer treatments by editing the genes inside the T-cells.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/27125551111/in/album-72157666320520263/">Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>Training the immune cells to find and kill cancer</h2>
<p>The first step in making these tumor-killing cells used in the cancer drug trial was to isolate the T-cells – a type of white blood cells that fights pathogens and cancer cells – from the blood of the cancer patients. Two patients with advanced <a href="https://www.cancer.gov/types/myeloma">multiple myeloma</a> and one patient with <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/myxoid-liposarcoma">myxoid/round cell liposarcoma</a> were enrolled for this study. </p>
<p>To arm the T-cells and bolster their tumor-fighting skills without harming normal cells, scientists genetically engineered the T-cells – disabling three genes and adding one gene – before returning them to the patients.</p>
<p>The first two of these deleted genes encode T-cell receptors, which are proteins found on the surface of the T-cells that can recognize and bind specific molecules, known as antigens, on cancer cells. When these engineered T-cells bind to these antigens, it allows them to attack and directly kill the cancer cells. But the problem is that a single T-cell can recognize multiple different antigens in the body, making them less focused on finding the cancer cells. By eliminating these two genes, the T-cells are less likely to attack the wrong target or the host, a phenomenon called autoimmunity, </p>
<p>In addition, they disrupted a third gene, called programmed cell death protein 1, which slows down the immune response. Disabling the programmed cell death protein 1 gene improves the efficiency of T-cells. </p>
<p>The final step in the transformation of these cells was adding a gene which produces a new T-cell receptor that recognizes and grabs onto a specific marker on the cancer cells called NY-ESO-1. With three genes deleted and one added, the T-cells are now ready to fight cancer.</p>
<h2>Where is CRISPR in this clinical trial?</h2>
<p>So how exactly did this team edit a T-cell? They utilized CRISPR/Cas9 gene editing technology that uses two components: a guide CRISPR molecule that finds and binds the target gene site; and a molecular scissor, Cas9, that snips the DNA, ultimately disabling the gene.</p>
<p>The team used electroporation, a technology that creates temporary holes in the cell membrane, to deliver the Cas9 protein along with the guide molecules that targeted the three genes of interest in millions of T-cells. </p>
<p>After disrupting the three genes with CRISPR, the team used a safe, deactivated virus to deliver a gene to the T-cell that would enable it to recognize the cancer-specific marker – NY-ESO-1. Removing these genes from millions of cells and then allowing the T-cells to multiply into billions of cells outside the body in petri dishes can take several days to weeks. </p>
<p>Four days before injecting the CRISPR-modified T-cells, the team gave each of the three patients several doses of chemotherapy drugs to deplete the existing white blood cells in their bodies. </p>
<p>Finally, approximately <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769084/">100 million modified T-cells per kilogram</a> of body weight were injected into the patients as a single infusion. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=379&fit=crop&dpr=1 600w, https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=379&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=379&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=476&fit=crop&dpr=1 754w, https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=476&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/301982/original/file-20191115-66945-ycyjnb.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=476&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">After modifying the T-cells by clipping out three genes with CRISPR and adding a new one, the immune cell becomes better at locating and killing cancer cells.</span>
<span class="attribution"><span class="source">Piyush Jain</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Promising future of CRISPR</h2>
<p>The team monitored the patients continuously for the first 28 days after injecting the T-cells. Then they followed up monthly for six months; after that every three months by monitoring any adverse events such as immune reaction. The T-cell therapy is frequently associated with various side effects such as fever, muscle pain, headaches, confusion, seizures, low blood pressure, bleeding disorders and multiple organ dysfunction. The team noted no signs of toxicity in any patient, which is exciting.</p>
<p>But the first patient with advanced multiple myeloma had continued growth of a tumor after 60 days. While the treatment seemed not so successful for the first patient, the <a href="https://clinicaltrials.gov/ct2/show/NCT03399448?term=parker&cond=CRISPR&draw=2&rank=1">phase 1 clinical trial</a> is mainly designed to test the safety, and the team reported no toxicity to any patient. </p>
<p>The second patient with advanced myxoid/round cell liposarcoma was monitored using serial CT scans and seemed stable after 90 days. The third patient with multiple myeloma started the trial recently and is too early for any results. The fact that there were no serious toxicity issues with this new therapy involving the CRISPR-based gene editing technology in cancer patients is a remarkable step toward the broad use in the clinic. </p>
<p>[ <em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters/weekly-highlights-61?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=weeklysmart">You can get our highlights each weekend</a>. ]</p><img src="https://counter.theconversation.com/content/126806/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Piyush K. Jain does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>In a new study, a team of US scientists have used gene editing to change the genetic code of white blood cells and transform them into more efficient tumor fighting cells. How did they do it?Piyush K. Jain, Assistant Professor, Department of Chemical Engineering, Herbert Wertheim College of Engineering, UF Health Cancer Center, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1253452019-10-30T12:57:05Z2019-10-30T12:57:05ZSuper-soldier T-cells fight cancer better after a transformational DNA delivery<figure><img src="https://images.theconversation.com/files/298005/original/file-20191021-56194-145vhts.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Delivering DNA to immune cells is the trickiest part of developing new gene-based therapies.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/dna-delivery-logo-icon-design-1020055285?src=tm7y2e5WjiSFAu5jUhfo-A-1-26">SAK Design/SHutterstock.com</a></span></figcaption></figure><p>I enjoy online shopping. However, I often find myself fussing about the delivery options during checkout. This is because not all delivery services are equally efficient and stress-free. </p>
<p>This personal experience has also inspired my research. As a <a href="https://scholar.google.com/citations?user=22Jx6scAAAAJ&hl=en&oi=ao">postdoctoral scholar</a> at <a href="https://www.meloshgroup.com/">Stanford University</a>, I have engineered tiny nano-materials – objects about 10,000 times smaller than a grain of rice – to better deliver DNA into white blood cells called T-cells that defend us against cancer. <a href="https://doi.org/10.1002/adtp.201900133">My method</a> – which I think of as the equivalent of FedEx and UPS – delivers DNA efficiently to T-cells that then transforms them into super-soldiers for tracking and attacking cancer cells. </p>
<h2>The promise of immuno-medicine</h2>
<p>Despite decades of research, cancer remains a challenging disease to treat because cancer cells mutate rapidly, becoming resistant to treatments such as chemotherapeutic drugs and radiation. The World Health Organization estimates that in 2018, <a href="https://www.who.int/news-room/fact-sheets/detail/cancer">close to 10 million individuals died of cancer</a>. The estimated <a href="https://www.who.int/news-room/fact-sheets/detail/cancer">economic cost</a> due to treatments and lost productivity when patients couldn’t work during treatment was a whopping US$1.2 trillion, and this is expected to increase with an aging population.</p>
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<a href="https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/297999/original/file-20191021-56211-skkuvh.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="attribution"><span class="source">Andy Tay</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/297998/original/file-20191021-56207-19z5679.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">These are figurines from a toy kit called ‘Rainbow Heroes.’ I created the kit with the Stanford Design School to educate children with cancer aged 5-10 about cancer immunotherapy. The black figurines represent the ‘enemy’ cancer cells while the colorful figurines are the ‘hero’ immune cells.</span>
<span class="attribution"><span class="source">Andy Tay</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>In the 1990s James Allison and Tasuku Honjo, who won the <a href="https://www.nobelprize.org/prizes/medicine/2018/summary/">2018 Nobel Prize in Medicine or Physiology</a> for cancer immunotherapy, discovered that cancer cells can inhibit T-cells and prevent them from detecting tumor cells. They pioneered a strategy using proteins called antibodies to bind to cancer cells. This prevents the cancer cells from interfering with T-cells and suppressing them.</p>
<p>The second type of cancer immunotherapy, which I study, involves genetically engineering T-cells with tailored DNA. The DNA I insert into T-cells encodes proteins that function like weapons that kill cancer cells faster before they get a chance to develop new mutations.</p>
<p>Unfortunately, it isn’t easy to deliver DNA into cells, and the existing methods are inadequate and may compromise the cancer-fighting functions of T-cells. Some T-cells may become hyperactive after DNA delivery and attack the patients’ own organs.</p>
<h2>Improving DNA delivery</h2>
<p>There are two predominant ways to deliver DNA into T-cells. The first uses viruses to deliver DNA. The second uses bulk electroporation, a technique that uses electricity to punch holes in the cells allowing the DNA to enter. However, both are inefficient and have several disadvantages. </p>
<p>Viruses insert their own viral DNA into host cells alongside the therapeutic DNA during delivery. This is dangerous, as the long-term consequence of having viral genes in our body is unknown. Viruses can also trigger <a href="https://doi.org/10.1016/S0163-7258(98)00020-5">toxic immune responses</a> such as persistent fever and even <a href="https://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html">death</a>. Another disadvantage is that viruses can carry only small packages of DNA, making it difficult to cram the latest gene editing tools inside them. </p>
<p>These shortcomings paved the way for electroporation. This method works by subjecting cells to strong electric fields that create holes in cells’ membrane and allow DNA to pass through. However, this technique is akin to a courier blasting holes in a person’s home to deliver packages. I and others have shown that this approach <a href="https://doi.org/10.1002/adtp.201900133">harms the T-cells</a> and <a href="https://doi.org/10.1073/pnas.1809671115">dampens their cancer-fighting ability</a>. </p>
<h2>The power of nano-engineering</h2>
<p>To bridge this technological gap, <a href="https://doi.org/10.1002/adtp.201900133">I have developed a new technique</a> named magnetic nano-electro-injection, or MagNEI, that can deliver DNA into T-cells up to four times more efficiently than virus and bulk electroporation. This is necessary to produce high numbers of genetically engineered T-cell soldiers – one billion or so – needed to fight cancer. </p>
<p>This is how MagNEI works. I first decorate the T-cells with FDA-approved magnetic particles to activate them and make them more receptive to DNA delivery. Then I use magnets to secure these cells onto hollow nano-tubes. These tubes are 10,000 times smaller in diameter than a grain of rice. Next, electric fields are applied through the nano-tubes to create small pores, or tunnels, into the cell membrane for DNA to enter cells. Magnetic forces then direct DNA into the nucleus of the cell. This is a much gentler procedure than electroporation.</p>
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<a href="https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=273&fit=crop&dpr=1 600w, https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=273&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=273&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=343&fit=crop&dpr=1 754w, https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=343&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/298974/original/file-20191028-113987-kmkci7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=343&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Left: T-cell decorated with magnetic particles that activate it, preparing it for DNA delivery. Right: Scanning electron microscopic image of hollow nano-tubes.</span>
<span class="attribution"><span class="source">Andy Tay</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>New metrics to assess delivery techniques</h2>
<p>Besides looking at DNA delivery efficiency – the percentage of cells that are successfully transformed with genetically engineered DNA – it is also important to consider the other consequences of various delivery methods. For example, I have found that the ability of engineered T-cell soldiers to migrate and hunt down cancer cells can be weaker after DNA delivery. </p>
<p>In my opinion, the cancer immunotherapy community needs to expand beyond simple assessments such as efficiency and cell survival to evaluate the utility of new DNA delivery techniques. </p>
<p>Therefore, in a recent review, <a href="https://doi.org/10.1021/acs.accounts.9b00272">I proposed a framework with new criteria</a> for evaluating which DNA delivery methods are most effective. One way to assess the impact of DNA delivery is to measure how the activity of specific genes are altered by the delivery of foreign DNA. </p>
<p>For instance, I found that bulk electroporation causes significant changes in the activity of genes linked to metabolism. That may explain why cells treated with this method grow slowly. This reduction in cell growth can increase manufacturing costs of these engineered T-cells and lengthen the treatment time for patients. </p>
<p>Magnet-based nano-scale methods such as mine offer advantages over virus and bulk electroporation for DNA delivery, but thus far, I have tested them only in animal studies and in experiments outside of human bodies. In the future, I hope to use nano-materials for delivering DNA to create cell-based therapies.</p>
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<p class="fine-print"><em><span>Andy Tay does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers are trying to boost the power of our immune system by genetically altering our white blood cells and transforming them into super-soldiers to fight cancer.Andy Tay, Postdoctoral Research Fellow in Materials Science and Engineering, Stanford UniversityLicensed as Creative Commons – attribution, no derivatives.