tag:theconversation.com,2011:/nz/topics/white-blood-cells-22843/articlesWhite blood cells – The Conversation2021-05-09T19:45:40Ztag:theconversation.com,2011:article/1600982021-05-09T19:45:40Z2021-05-09T19:45:40ZTaking one for the team: 6 ways our cells can die and help fight infectious disease<figure><img src="https://images.theconversation.com/files/399422/original/file-20210507-15-1umzp1t.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C389%2C243&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">White blood cells dying</span> </figcaption></figure><p>We have all heard of COVID-19, the flu and bacterial infections. But what is actually happening to our cells when we contract these diseases? Many of our body’s cells don’t live to tell the tale. But cell death isn’t necessarily a bad thing — in fact, the death of infected cells can provide a sacrificial mechanism to stop pathogens in their tracks before they can spread through our body. </p>
<p>Over the years, researchers have realised there are many ways for our cells to die. Our genetics contain a comprehensive “licence to die”, with the route to cell death dictated by both the type of the cell and the pathogen. Let’s check some out:</p>
<h2>The dancing death</h2>
<p>In the time it takes you to read this sentence, ten million cells in your body will have died, through a type of death called <em>apoptosis</em>. This term, coined in 1972 by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008650/">Australian pathologist John Kerr</a>, comes from the Greek phrase for “leaves falling from a tree”.</p>
<p>Apoptosis is the most common form of cell death, and has also been nicknamed the “dance of death”, because of the extraordinary shape changes exhibited by the cells under a microscope as they sacrifice themselves. </p>
<p>For example, apoptotic cells dying from radiation or <a href="https://www.nature.com/articles/s42003-020-0955-8">infection with influenza A virus</a> (aka, the flu) generate large, bubble-like structures on their surface called blebs, before shooting out long beaded necklace-like protrusions and finally shattering into pieces. </p>
<p>The death of flu-infected cells is suggested to both <a href="https://www.nature.com/articles/s41419-018-1035-6">aid and limit viral spread</a>. Nevertheless, it’s a spectacular event to witness (and an excellent reminder to get your flu shot this winter).</p>
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<figcaption><span class="caption">White blood cell blebbing and dying.</span></figcaption>
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<h2>Out with a bang</h2>
<p>Vaccinia virus is used worldwide to vaccinate against <a href="https://www.who.int/news-room/feature-stories/detail/smallpox-vaccines">smallpox</a>. In fact, it was the very first vaccine, developed in 1796 by Edward Jenner.</p>
<p>We now also know that vaccinia virus can make our cells more sensitive to a particular type of cell death, caused by a molecule called <a href="https://www.cell.com/fulltext/S0092-8674(09)00642-4">TNF</a>. This can help prevent the disease spreading by killing off infected cells before the virus has a chance to replicate.</p>
<p>Many of our cells have a roughly spherical or balloon-like shape, encapsulated by a protective layer called the cell membrane. Just like bursting a balloon with a pin, puncture to the cell membrane marks the point of no return.</p>
<p>This process occurs during <a href="https://www.nature.com/articles/s41467-020-16887-1"><em>necroptosis</em></a> — an explosive type of cell death in which proteins inside the cell punch holes in the membrane. The cell pops and dies, shutting down the machinery needed for viral replication.</p>
<h2>The spider web of death</h2>
<p>When they aren’t busy haunting our nightmares, spiders can be found weaving silken masterpieces of extraordinary detail and strength. The web of a <a href="https://australian.museum/learn/animals/spiders/golden-orb-weaving-spiders/">golden orb weaving spider</a>, for example, is strong enough to entangle small birds. </p>
<p>On a smaller but equally impressive scale, our immune system contains specialised cells called neutrophils that can weave a deadly web of their own and entrap bacteria. Neutrophils gallantly sacrifice themselves in the process of casting their web, in a type of cell death perhaps fittingly called <em>NETosis</em>. </p>
<p>When infected with bacteria such as <em><a href="https://link.springer.com/article/10.1007/s00281-013-0384-6">Streptococcus pneumoniae</a></em>, which causes pneumonia and meningitis, neutrophils eject a specialised web made from their own DNA. These webs can entangle nearby bacteria to prevent their escape until other immune cell reinforcements arrive to clear the infection. Sometimes, proteins found in these webs can also kill the bacteria - quite an impressive defence mechanism!</p>
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<a href="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cartoon illustrating different forms of cell death" src="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=662&fit=crop&dpr=1 600w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=662&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=662&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=832&fit=crop&dpr=1 754w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=832&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=832&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">There are a surprising number of ways cells can lay down their lives for the greater good.</span>
<span class="attribution"><span class="license">Author provided</span></span>
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<h2>The last meal</h2>
<p>Just as our bodies are compartmentalised into organs such as the stomach, liver or heart, our individual cells also have specialised compartments. One of the cell’s “stomachs” (a structure called the “autophagosome”) engulfs and digests cellular contents such as damaged molecules through the process of <em>autophagy</em>.</p>
<p>However, in some circumstances, the machinery that drives this Pac-Man-style action can also facilitate the cell’s demise. Coincidentally, the bacteria <em>Helicobacter pylori</em> can infect cells of the human stomach lining, called epithelial cells, which can cause ulcers and gastritis. The cells can respond with a process called <a href="https://www.nature.com/articles/s41419-017-0011-x">autophagic cell death</a>, in which the induction of autophagy causes the cell to die. </p>
<h2>A fiery death</h2>
<p>Pyromania, derived from the Greek word <em>pyr</em>, meaning fire, is an obsessive desire to set things ablaze. Some of our immune cells also have the ability to self-immolate and cause inflammation as part of our response to infection.</p>
<p>Since its relatively recent discovery in <a href="https://pubmed.ncbi.nlm.nih.gov/11303500/">2001</a>, this type of cell death, called <em>pyroptosis</em>, has become a hot topic (sorry) among cell biologists, and is often facilitated by a molecular complex called the <a href="https://www.sciencedirect.com/science/article/pii/S0092867410000759">inflammasome</a>.</p>
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Read more:
<a href="https://theconversation.com/what-is-autoinflammatory-disease-the-rare-immune-condition-with-waves-of-fever-128696">What is autoinflammatory disease, the rare immune condition with waves of fever?</a>
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<p>In 2021, understanding pyroptosis is more important than ever, as it has been linked to <a href="https://www.jimmunol.org/content/205/2/307">infection with SARS-CoV-2 infection</a>, the virus that causes COVID-19.</p>
<p>Activation of the factors that cause pyroptosis may help explain the excessive inflammation seen in patients with severe COVID-19. And this could potentially offer a new way to combat the disease.</p>
<h2>Overdosing on iron and fat</h2>
<p>There’s no doubt the key to a long and healthy life is a balanced diet and exercise. However, sometimes we can’t resist the urge to devour a burger and fries with ice cream for dessert. With enough hard work, we can burn it off again. But for individual cells, overindulging can be fatal. </p>
<p>Too much iron and/or harmful types of fat molecules can cause cells to die by <em>ferroptosis</em>. Cells infected with <em><a href="https://rupress.org/jem/article/216/3/556/120345/A-major-role-for-ferroptosis-in-Mycobacterium">Mycobacterium tuberculosis</a></em>, the bacterium that causes TB, can increase their iron content and cause ferrototic cell death! Pass the salad, thanks.</p>
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Read more:
<a href="https://theconversation.com/tick-tock-how-stress-speeds-up-your-chromosomes-ageing-clock-127728">Tick, tock... how stress speeds up your chromosomes' ageing clock</a>
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<p>The survival of the human body is a fine balancing act between cell growth and cell death. Understanding our cells’ complex “licence to die” could give us new ways to combat disease.</p><img src="https://counter.theconversation.com/content/160098/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Georgia Atkin-Smith receives funding from the CASS Foundation (Medicine/Science Grant) and is a postdoctoral researcher at both La Trobe University and the Walter and Eliza Hall Institute of Medical Research.</span></em></p><p class="fine-print"><em><span>Ivan Poon receives funding from the National Health and Medical Research Council and the Australian Research Council. Ivan is an Associate Professor at the La Trobe Institute for Molecular Science. </span></em></p>The survival of the human body is a fine balancing act between cell growth and cell death. Understanding our cells’ complex “licence to die” could give us new ways to combat disease.Georgia Atkin-Smith, Research scientist, La Trobe UniversityIvan Poon, Associate Professor, Biochemistry, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag: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/1406012020-06-15T13:48:56Z2020-06-15T13:48:56ZAutoimmune diseases: we discovered how to turn white blood cells from attacking the body to protecting it<figure><img src="https://images.theconversation.com/files/341837/original/file-20200615-65952-vd1u3k.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C6071%2C4041&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We shown how to stop immune cells from attacking the nervous system cells.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/smiling-handsome-boyfriend-wheelchair-girlfriend-coffee-1212056776">LightField Studios/ Shutterstock</a></span></figcaption></figure><p>For most of us, the immune system works to protect us from bacteria, viruses, and other harmful pathogens. But for people with autoimmune conditions, the body’s white blood cells instead perceive other cells and tissues in the body to be a threat and attacks them. While some immune disorders, like allergies, can sometimes be treated, autoimmune conditions such as multiple sclerosis (MS) remain incurable. </p>
<p>Our research has shown that you can stop the immune system attacking the nerves – which is what happens in MS. We did this by <a href="https://www.nature.com/articles/ncomms5741">giving the immune system</a> ever-increasing doses of the same molecule that the immune system was attacking.</p>
<p>Now we’ve taken this research one step further to show <a href="https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30728-2">how this process works</a> inside the white blood cells that make up the immune system. Our team revealed the complex mechanisms that allow us to switch T cells (a type of white blood cell) from attacking the cells of autoimmune disease patients to protecting them. We learnt how to make reactive T cells tolerant. </p>
<p>Our T cells have evolved so that each one recognises different parts of the molecules made by pathogens (also known as antigens). When the T cells recognise antigens, the T cells start multiplying in order to attack the invaders. The T cells move from a resting state into a highly activated state by turning on immune response genes that help them attack pathogens.</p>
<p>When an infection is over, some of these T cells remain, giving lifelong immunity as <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/memory-t-cell">memory T cells</a>. They’re able to carry this <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/bies.201600184">lifelong memory</a> by imprinting our chromosomes with triggers that allow immune response genes to be reactivated much faster.</p>
<p>In autoimmune diseases such as MS, Graves’ disease and type 1 diabetes, the immune system gets it wrong. In MS, the T cells start to see <a href="https://pubmed.ncbi.nlm.nih.gov/16794783/">myelin basic protein</a>, a component of the outside, insulating coating that surrounds nerve cells, as an antigen. They attack the nervous system and, as a result, MS sufferers lose control over their muscles. Our research is trying to rectify this.</p>
<h2>Weakening T cells</h2>
<p>To help us understand this process, we focused on the T cells that specifically recognise myelin basic protein as an antigen. We found that over time these T cells became less reactive after they were exposed to gradually increasing doses of the myelin basic protein. </p>
<p>This progressive exposure reprogrammed these T cells so that the signals telling the cells to attack the protein became weaker. This converted the T cells from attacking to protecting.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/341455/original/file-20200612-153858-1p37pr9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">White blood cells normally protect against diseases.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-white-blood-cell-leukocyte-1108335812">microstock3D</a></span>
</figcaption>
</figure>
<p>This switch could be explained by the fact that the immune system is regulated by two types of genes. One type tells the immune system to attack, while the other gene type silences the immune system to stop it going out of control. </p>
<p>We showed that when T cells are made tolerant, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/ctla-4">two</a> <a href="https://pubmed.ncbi.nlm.nih.gov/21061197/">of the most important genes</a> that suppress the immune system were reprogrammed at the level of the chromosome to keep them more active. Repetitive exposure to the myelin basic protein imprinted a memory within these inhibitory genes. This allowed T cells to remember to inhibit the T cell receptor from sending attack signals when they encountered that same specific myelin basic protein fragment.</p>
<p>The end effect of turning on the inhibitory genes was to weaken the signals inside T cells that would normally turn on other genes that activate the immune system. That meant that the T cells stopped getting the signal telling them to attack nerve cells. </p>
<p>Autoimmune diseases are currently treated using immunosuppressive drugs. The problem with this is that they suppress the whole immune system, making the patient prone to cancers and other infections. Trials using antigen therapy in patients with MS and <a href="https://www.liebertpub.com/doi/full/10.1089/thy.2019.0036">Grave’s disease</a> are ongoing, but results from short-term preliminary <a href="https://n.neurology.org/content/90/11/e955">clinical trials</a> showed both MS and Graves’ disease patients started to have improved health while the trials lasted.</p>
<p>One day we hope that antigen-based immunotherapy will be able to deliver major benefits for all types of autoimmune disease. By detailing the complex mechanisms that control the fate of self-reactive T cells, we may have also opened the door for more specific therapies for these diseases.</p><img src="https://counter.theconversation.com/content/140601/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Cockerill receives funding from the Medical Research Council to study epigenetic reprogramming of genes in memory T cells. I have no conflicts of interest relating to this article.</span></em></p><p class="fine-print"><em><span>David Wraith consults for Apitope International NV, a company focusing on antigen-specific immunotherapy of autoimmune disease and receives funding from the Medical Research Council and EU.</span></em></p>Our research has found a way of switching immune system cells from attacking to protecting.Peter Cockerill, Professor, Institute of Cancer and Genomic Sciences, University of BirminghamDavid C. Wraith, Professor of Immunology and Director, Institute of Immunology and Immunotherapy, University of Birmingham, University of BirminghamLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1371452020-05-05T12:20:41Z2020-05-05T12:20:41ZYour genes could determine whether the coronavirus puts you in the hospital – and we’re starting to unravel which ones matter<figure><img src="https://images.theconversation.com/files/332506/original/file-20200504-83725-1ijhd03.jpg?ixlib=rb-1.1.0&rect=286%2C0%2C8411%2C4900&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The relationship between the coronavirus and human genetics is murky. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/virus-cells-attacking-a-dna-strand-royalty-free-image/1183281148?adppopup=true">fatido/E+ via Getty Images</a></span></figcaption></figure><p><em>The Research Brief is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>When some people become infected with the coronavirus, they only develop <a href="https://theconversation.com/infected-with-the-coronavirus-but-not-showing-symptoms-a-physician-answers-5-questions-about-asymptomatic-covid-19-137029">mild or undetectable cases of COVID-19</a>. Others suffer severe symptoms, fighting to breathe on a ventilator for weeks, if they survive at all. </p>
<p>Despite a concerted global scientific effort, doctors <a href="https://fivethirtyeight.com/features/why-are-some-young-healthy-people-getting-severe-covid-19/">still lack a clear picture</a> of why this is. </p>
<p>Could genetic differences explain the differences we see in symptoms and severity of COVID-19?</p>
<p>To test this, we used computer models to analyze known genetic variation within the human immune system. The <a href="https://dx.doi.org/10.1128/JVI.00510-20">results of our modeling</a> suggest that there are in fact differences in people’s DNA that could influence their ability to respond to a SARS-CoV-2 infection.</p>
<h2>What we did</h2>
<p>When a virus infects human cells, the body reacts by turning on what are essentially anti-virus alarm systems. These alarms identify viral invaders and tell the immune system to send cytotoxic T cells – a type of white blood cell – to destroy the infected cells and hopefully slow the infection.</p>
<p>But not all alarm systems are created equal. People have different versions of the same genes – called alleles – and some of these alleles are more <a href="https://dx.doi.org/10.1128%2FCMR.00048-08">sensitive to certain viruses or pathogens than others</a>. </p>
<p>To test whether different alleles of this alarm system could explain some of the range in immune responses to SARS-CoV-2, we first retrieved a list of all the proteins that make up the coronavirus from an <a href="https://www.ncbi.nlm.nih.gov/refseq/">online database</a>.</p>
<p>We then took that list and used existing computer algorithms to predict how well different versions of the anti-viral alarm system detected these coronavirus proteins. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=802&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=802&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=802&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1008&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1008&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1008&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 model of an HLA protein (green and yellow) bound to a piece of a virus (orange and blue) – in this case, influenza.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/HLA-B27#/media/File:HLA-B*2705-peptide_in_complex_with_influenza_nucleoprotein_NP383-391.png">Prot reimage via Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>The part of the alarm system that we tested is called the human leukocyte antigen system, or HLA. Each person has multiple alleles of the genes that make up their HLA type. Each allele codes for a different HLA protein. These proteins are the sensors of the alarm system and find intruders by binding to various peptides – chains of amino acids that make up parts of the coronavirus – that are foreign to the body.</p>
<p>Once an HLA protein binds to a virus or piece of a virus, it transports the intruder to the cell surface. This “marks” the cell as infected and from there the immune system will kill the cell.</p>
<p>In general, the more peptides of a virus that a person’s HLAs can detect, the <a href="https://dx.doi.org/10.4049%2Fjimmunol.1302101">stronger the immune response</a>. Think of it like a more sensitive sensor of the alarm system. </p>
<p>The results of our modeling predict that some HLA types bind to a large number of the SARS-CoV-2 peptides while others bind to very few. That is to say, some sensors may be better tailored to SARS-CoV-2 than others. If true, the specific HLA alleles a person has would likely be a factor in how effective their immune response is to COVID-19. </p>
<p>Because our study only used a computer model to make these predictions, we decided to test the results using clinical information from the 2002-2004 SARS outbreak.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1216&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1216&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1216&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1528&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 section of DNA that codes for HLAs is on the sixth chromosome.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HLA_MHC_Complex_illustration.jpg">Pdeitiker at English Wikipedia / Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We found similarities in how effective alleles were at identifying SARS and SARS-CoV-2. If an HLA allele appeared to be bad at recognizing SARS-CoV-2, it was also bad at recognizing SARS. Our analysis predicted that one allele, called B46:01, is particularly bad with regards to both SARS-CoV-2 and SARS-CoV. Sure enough, previous studies showed that people with this allele tended to have more <a href="https://doi.org/10.1186/1471-2350-4-9">severe SARS infections</a> and higher viral loads than people with other versions of the HLA gene. </p>
<h2>What’s next?</h2>
<p>Based on our study, we think variation in HLA genes is part of the explanation for the huge differences in infection severity in many COVID-19 patients. These differences in the HLA genes are probably not the only genetic factor that affects severity of COVID-19, but they may be a significant piece of the puzzle. It is important to further study how HLA types can clinically affect COVID-19 severity and to test these predictions using real cases. Understanding how variation in HLA types may affect the clinical course of COVID-19 could help identify individuals at higher risk from the disease.</p>
<p>To the best of our knowledge, this is the first study to evaluate the relationship between viral proteins across a wide range of HLA alleles. Currently, we know very little about the relationship between many other viruses and HLA type. In theory, we could repeat this analysis to better understand the genetic risks of many viruses that currently or could potentially infect humans.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/137145/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Reid Thompson receives funding from the Department of Veterans Affairs, and the Sunlin and Priscilla Chou Foundation. </span></em></p><p class="fine-print"><em><span>Abhinav Nellore and Austin Nguyen do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers from Oregon Health and Science University found that variations in genes that code for parts of the cellular alarm system might play a role in how well people fight off COVID-19.Austin Nguyen, PhD Candidate in Computational Biology and Biomedical Engineering, Oregon Health & Science UniversityAbhinav Nellore, Assistant Professor of Biomedical Engineering & Surgery, Oregon Health & Science UniversityReid Thompson, Assistant Professor of Radiation Medicine, Oregon Health & Science UniversityLicensed 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/900672018-01-15T16:06:50Z2018-01-15T16:06:50ZRevealed: adult leukaemia can be caused by gene implicated in breast cancer and obesity<figure><img src="https://images.theconversation.com/files/201962/original/file-20180115-101505-1tj72tw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">AML under the microscope. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/blood-smear-under-microscopy-showing-on-550330186?src=1RRsQj8cvHJjbcMN_p5BAw-1-37">Medtech THAI STUDIO LAB 249</a></span></figcaption></figure><p>When people think of leukaemia, they usually think of blood cancers that affect children. These mostly come under the category of acute lymphoblastic leukaemia – or ALL – and are different to the group of blood cancers which predominantly affect adults over the age of 60, known as acute myeloid leukaemia (AML). </p>
<p>AML accounts for about 90% of all leukaemias in adults, though it affects some children too. With <a href="http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-aml/incidence#heading-One">some 3,000</a> new cases each year in the UK alone, it is tougher to treat than ALL. </p>
<p>Where advances in ALL treatment have raised survival rates to <a href="https://www.stjude.org/disease/acute-lymphoblastic-leukemia-all.html">around 90%</a> over the past several decades, the rates for surviving the less well researched AML are <a href="https://www.healthline.com/health/acute-myeloid-leukemia-survival-rates-outlook">more like</a> 65%. Older adults respond least well to treatment, with only 5% of over-65s surviving more than five years. </p>
<p>I am therefore pleased to report a promising discovery. Work in which I have been involved has shown that a particular gene can play a critical role in the development of the disease. This could be the precursor to a breakthrough that could be life-saving for patients. </p>
<h2>Cells and treatments</h2>
<p>Your bone marrow contains stem cells which divide and differentiate into red blood cells and the main groups of white blood cells – myeloid cells, neutrophils and lymphocytes. Normally this happens in a very controlled manner, ensuring you have all the red blood cells needed to carry oxygen around your body, and all the white blood cells needed to fight off infections. </p>
<p>In AML too many immature myeloid cells are produced too quickly by the bone marrow. They are mutant cells which don’t mature, meaning they fail to defend against infection. </p>
<p>For this reason, early signs of AML include flu-like symptoms, aches and pains in the joints, and rapid weight loss. As the abnormal cells build up inside the bone marrow or the blood they grow and divide aggressively. Left untreated, AML patients can have only weeks to live. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=913&fit=crop&dpr=1 600w, https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=913&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=913&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1148&fit=crop&dpr=1 754w, https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1148&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/201963/original/file-20180115-101505-e9kfw7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1148&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bone marrow transplant.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bone-marrow-transplant-operation-786989008?src=V3Gd5UZImFRTdR5V6xaclg-1-7">El-Roi</a></span>
</figcaption>
</figure>
<p>Patients are normally treated by two stages of chemotherapy over a few months: an induction phase which reduces the number of cancer cells to undetectable levels, then a consolidation phase to kill any cancerous cells hiding in the body. Patients often also receive a bone marrow transplant, effectively giving them a new immune system. </p>
<p>Treating AML is complicated by patients generally being older, since they tolerate the intensive chemotherapy less well. In many cases, they receive some treatment and end up only living a few months. Better understanding the mutations to develop more targeted and less harsh treatments looks like the key to improving survival. </p>
<h2>Step forward, PTPN1</h2>
<p>A number of mutations are associated with AML, and often occur in combinations. It’s these mixtures of mutations that are thought to cause the <a href="https://www.cancer.org/cancer/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html">complex subtypes</a> of cancers within the AML group. One common mutation is called <a href="http://www.cytocell.com/probes/23-del20q-deletion">Del20q</a>. It involves the deletion of part of <a href="https://ghr.nlm.nih.gov/chromosome/20">chromosome 20</a>, one of the 23 pairs of chromosomes most humans have in all their cells. </p>
<p>It has <a href="http://www.bloodjournal.org/content/bloodjournal/82/11/3424.full.pdf?sso-checked=true">long been suspected</a> that genes on this part of the chromosome may function, either individually or together, to suppress cancer. Until recently, however, researchers have found it hard to say which genes are responsible. </p>
<p>One candidate is known as PTPN1, or protein tyrosine phosphatase, non-receptor type 1. First discovered in the late 1980s and linked to metabolic function, it is more famously known for its roles in <a href="https://www.ncbi.nlm.nih.gov/pubmed/27465552">breast cancer</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/25120222">type 2 diabetes</a>. Its location on chromosome 20 has long made specialists suspect it could also be involved in AML. </p>
<p>It was <a href="https://www.nature.com/articles/leu201731">shown recently</a> that when you switch off the equivalent gene in mice, it leads to what are known as <a href="https://www.cancersupportcommunity.org/myeloproliferative-neoplasms">myeloproliferative neoplasm</a>, which is the wider family of blood cancers of which AML is a member. In <a href="http://cancerres.aacrjournals.org/content/early/2017/11/09/0008-5472.CAN-17-0946">our new study</a>, we have taken this a step forward: we have shown that if you delete this gene in older mice, it specifically gives rise to AML – and in a similar way to how the disease develops in older humans. </p>
<p>The previous study showed that PTPN1 is deleted from chromosome 20 in the cells of patients in around 17% of AML cases, which raises questions about the remaining majority of cases. We were able to show that deleting the mouse equivalent of PTPN1 activates a molecule called STAT3, which is important to regulating cell growth and division. </p>
<p>If a patient has too much STAT3, it leads to the generation of too many immature myeloid cells – that hallmark of AML I mentioned earlier. This is potentially a very useful finding for further studies into the genetics behind the disease: in the two other most common mutations linked to AML, which relate to a protein called JAK2 and a receptor called FLT-3, STAT3 is also over-activated. In all, STAT3 is relevant to maybe three quarters of all AML cases. Uncovering exactly how they relate looks critical to developing an eventual cure. </p>
<h2>The future</h2>
<p>In short, we’re closing in on understanding the links between PTPN1, STAT3 and AML. A few years from now, as the cost of genome sequencing falls, it will become a question of identifying which combination of mutations has affected a patient and prescribing a treatment accordingly. </p>
<p>This treatment will probably be more bespoke chemotherapy for patients that can tolerate it, and perhaps gene editing using tools such as <a href="https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr">CRISPR</a> for those that cannot. Doctors would edit the correct versions of genes like PTPN1 back into the patient’s bone marrow, potentially restoring normal function and negating the often difficult search for a compatible bone marrow donor. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/201964/original/file-20180115-101498-q5v593.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">New edition.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bone-marrow-transplant-operation-786989008?src=V3Gd5UZImFRTdR5V6xaclg-1-7">vchal</a></span>
</figcaption>
</figure>
<p>There is much research still to be done. We need to understand what PTPN1 is doing in healthy myeloid cells to grasp which processes are disturbed when it becomes deleted. The other big question is whether instead of getting deleted, PTPN1 sometimes more subtly mutates and how this relates to AML. Besides this, there are many other genes on the Del20q deletion that we need to better understand, too. </p>
<p>In the meantime, showing that removing PTPN1 leads to AML is an important piece of the puzzle. It brings the day closer when survival rates for AML make the same climb that we have seen in other kinds of leukaemia, and hopefully even beyond.</p><img src="https://counter.theconversation.com/content/90067/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Samantha Le Sommer does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Improvements in survival rates for acute myeloid leukaemia have failed to keep pace with other leukaemias. That may be about to change.Samantha Le Sommer, Postdoctoral Researcher, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/803272017-07-26T20:15:02Z2017-07-26T20:15:02ZBlood tests and diagnosing illness: what can blood tell us about what’s happening in our body?<figure><img src="https://images.theconversation.com/files/176715/original/file-20170704-12293-nwqqm7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Blood permeates every tissue in the body, meaning just a few spoonfuls can tell us a lot about our health. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p><em>This week we’re running a series in collaboration with the Australian Red Cross Blood Service looking at blood: what it actually does, why we need it, and what happens when something goes wrong. Read other articles in the series <a href="https://theconversation.com/au/topics/blood-series-39533">here</a>.</em></p>
<hr>
<p>Doctors have continually sought better ways of determining what is wrong with a patient. When you visit a GP’s office or emergency department with an unknown illness, a doctor will commonly draw some blood to gain a better idea of what’s going on inside your body. Blood is perhaps the most important window through which we can peer into a person’s health or illness.</p>
<p>About 7% of our body weight is our blood, and our heart spits out about five litres of blood every minute. Oxygenated blood leaves the left side of the heart via the aorta and the arteries - which permeate every tissue in the body - and returns to the right side of the heart via the veins. From the right side of the heart, blood is pumped into the lungs where it is oxygenated, returning to the left side of the heart.</p>
<p>In about two tablespoons of blood there’s a lot we can tell about our health.</p>
<h2>What blood can tell us</h2>
<p>When someone presents at an emergency department, the initial panel of tests will include a full blood count. This details the red blood cell count, white blood cell count and platelets; electrolytes (the substance in our blood that carries an electric charge that is vital for life) to measure kidney function; liver function tests and “C-reactive protein” which can tell us if there is inflammation somewhere in the body.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/177464/original/file-20170710-5553-yu4kic.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">Our blood can tell us how many of our organs are functioning.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
</figcaption>
</figure>
<p>From these tests we can determine things like the presence of anaemia (low red blood cells from various causes), infection, kidney failure and liver disease. Often the results of these tests will trigger further testing. For example, the presence of anaemia will usually lead to testing for iron deficiency, possibly vitamin B12 and folate, screening for haemolysis (destruction of red blood cells) and a measure of how well the bone marrow, which makes red blood cells, is responding. </p>
<p>If infection is suspected, blood will be drawn and transferred into a bottle that enables bacteria to grow. Bacteria in the blood is called septicaemia. The identification of the bacteria responsible significantly helps in the management, meaning the right antibiotics can be delivered to the patient.</p>
<hr>
<p><a href="https://theconversation.com/from-animal-experiments-to-saving-lives-a-history-of-blood-transfusions-80391"><em>Infographic - From animal experiments to saving lives: a history of blood transfusions</em></a></p>
<hr>
<p>Bruising or excessive bleeding will prompt assessment of platelets and clotting. Platelets are the first responders to injury, and if they are low or not functioning properly, they will allow bleeding to proceed unchecked. To tell if blood is clotting normally we need an additional teaspoon of blood. These clotting factors are synthesised in the liver, so they can also give us a warning about liver disease.</p>
<p>As a kidney specialist, my personal favourite are the electrolytes. Together with a urine test, blood electrolytes can measure someone’s kidney disease from stage one through to five. As kidney function declines, potassium levels increase in the blood and can reach dangerous levels. A high potassium count can cause a potentially fatal heart arrhythmia.</p>
<p>Liver function tests provide information on what the liver is producing and excreting - abnormalities of liver function could mean gall stones or hepatitis. Viral causes of hepatitis, such as Hepatitis B and C, can quickly be checked in the blood. We can also find out how recently the infection was acquired and whether chronic infection persists.</p>
<p>Cardiac enzymes in the blood tell us if a patient has had a heart attack. The enzymes are proteins released from damaged heart muscle, so the higher the level, the greater the damage to the heart.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/179116/original/file-20170721-30878-unhpag.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">Blood is an incredible window into the workings of the human body.</span>
<span class="attribution"><span class="source">Blood on Silk / Buy Sell by Fiona Davies (AUS) Courtesy of the artist as part of Science Gallery Melbourne’s BLOOD exhibition</span></span>
</figcaption>
</figure>
<h2>What can’t blood tell us?</h2>
<p>The repertoire of blood tests available to the treating doctor is vast. Other blood tests include screening for autoimmune disease, monitoring the response of cancers to treatment with tumour markers, assessing reproductive function, screening for genetic disorders during pregnancy and diagnosing pregnancy itself.</p>
<p>Despite this, sometimes a diagnosis remains elusive – frustrating for the patient and doctor alike. Neurological disease such as stroke, motor neurone disease, Alzheimer’s and multiple sclerosis aren’t diagnosable from blood tests. Similarly, the diagnoses of depression, schizophrenia, ADHD and autism lack a specific blood diagnostic marker.</p>
<p>The huge array of blood tests available to the clinician aid in a rapid diagnosis in many instances. But the choice and the interpretation of the test needs to be considered in light of the patient and their presenting symptoms. As the old adage in medicine says: treat the person and not the numbers.</p>
<hr>
<p><em><strong>Read other articles in the series:</strong></em></p>
<p><em><a href="https://theconversation.com/essays-on-blood-why-do-we-actually-have-it-75064">Essays on blood: why do we actually have it?</a></em></p>
<p><em><a href="http://theconversation.com/from-animal-experiments-to-saving-lives-a-history-of-blood-transfusions-80391">From animal experiments to saving lives: a history of blood transfusions</a></em></p>
<p><em><a href="http://theconversation.com/explainer-whats-actually-in-our-blood-75066">Explainer: what’s actually in our blood?</a></em></p>
<p><a href="http://theconversation.com/blood-groups-beyond-a-b-and-o-what-are-they-and-do-they-matter-75063"><em>Blood groups beyond A, B and O: what are they and do they matter?</em></a></p>
<p><em><a href="http://theconversation.com/what-can-go-wrong-in-the-blood-a-brief-overview-of-bleeding-clotting-and-cancer-76400">What can go wrong in the blood? A brief overview of bleeding, clotting and cancer</a></em></p><img src="https://counter.theconversation.com/content/80327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Karen Dwyer does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Blood is perhaps the most important window through which we can peer into a person’s health or illness.Karen Dwyer, Deputy Head, School of Medicine, Deakin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/750662017-07-24T20:12:06Z2017-07-24T20:12:06ZExplainer: what’s actually in our blood?<figure><img src="https://images.theconversation.com/files/170731/original/file-20170524-5786-oxlpch.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Our blood has more functions than we probably realise - all vital for life. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p><em>This week we’re running a series in collaboration with the Australian Red Cross Blood Service looking at blood: what it actually does, why we need it, and what happens when something goes wrong with the fluid that gives us life. Read other articles in the series <a href="https://theconversation.com/au/topics/blood-series-39533">here</a>.</em></p>
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<p>Blood is vitally important for our body. As it’s pumped around our body through veins and arteries, it transports oxygen from our lungs to all of the other organs, tissues and cells that need it. Blood also removes waste products from our organs and tissues, taking them to the liver and kidneys, where they’re removed from the body.</p>
<p>About 45% of our blood consists of different types of cells and the other 55% is plasma, a pale yellow fluid. Blood transports nutrients, hormones, proteins, vitamins and minerals around our body, suspended in the plasma. They provide energy to our cells and also signal for growth and tissue repair. The average adult has about five litres of blood.</p>
<p>The different types of blood cells include red blood cells, platelets, and white blood cells, and these are produced in the bone marrow, in the centre of our bones.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=306&fit=crop&dpr=1 600w, https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=306&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=306&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=384&fit=crop&dpr=1 754w, https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=384&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/177639/original/file-20170710-587-zksmvf.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=384&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">The Conversation</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<h2>Red blood cells</h2>
<p>Red blood cells are essential for transporting oxygen around the body. Red cells are very small, donut-shaped cells with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678251/">an average lifespan of 120 days</a> within the body. They contain a protein called haemoglobin, which contains iron and binds very strongly to oxygen, giving blood its red colour. </p>
<p>Red cells are flexible and able to squeeze through even the tiniest of our blood vessels, called capillaries, to deliver oxygen to all of the cells in our body. When the red cells reach our organs and tissues, haemoglobin releases the oxygen.</p>
<h2>Platelets</h2>
<p>Platelets are even smaller than red blood cells. In fact, they are tiny fragments of another much larger type of cell, called a megakaryocyte, which is located in the bone marrow. Platelets are formed by budding off from the megakaryocyte. Platelets have an average lifespan of eight to 10 days within the body, so they are constantly being produced. When body tissue is damaged, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925965/">chemicals are released that attract</a> platelets. </p>
<p>Platelets clump together and stick to the damaged tissue, which starts to form a clot to stop bleeding. Many of the proteins that help the clot to form are contained in plasma. Platelets also release growth factors that help with tissue healing.</p>
<hr>
<p><a href="https://theconversation.com/from-animal-experiments-to-saving-lives-a-history-of-blood-transfusions-80391"><em>Infographic - From animal experiments to saving lives: a history of blood transfusions</em></a></p>
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<h2>White blood cells</h2>
<p>Blood also carries white blood cells, which are an essential part of our immune system. Some white cells are able to kill micro-organisms by engulfing and ingesting them. Other types of white cells, called lymphocytes, release antibodies that help to fight infection.</p>
<p>Blood cells don’t act alone; they work together for normal body function. For example, when we cut our skin, platelets help plug the cut to stop it bleeding, plasma delivers nutrients and clotting proteins, white cells help to prevent the cut from becoming infected, and red cells deliver oxygen to help keep the skin tissue healthy.</p>
<h2>Blood transfusions</h2>
<p>Sometimes patients who are having surgery, cancer treatment or when they are seriously injured need a blood transfusion. This is usually because they have lost a lot of platelets, red cells or plasma, or because their cancer treatment has killed many of their blood cells.</p>
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<figcaption><span class="caption">The journey of blood.</span></figcaption>
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<p>In Australia, blood is donated by voluntary blood donors at the <a href="http://www.donateblood.com.au/">Australian Red Cross Blood Service</a>. A typical whole blood donation is just over 450 mL, and it takes around ten minutes to collect. Every time a donation is made, the donor is screened for infectious diseases such as hepatitis and HIV, so these aren’t transferred to the patient receiving the blood. </p>
<p>After donation, the blood is separated into its different parts: platelets, red cells and plasma, which are known as blood components. White cells are removed because they can cause problems in patients who receive them. Once the blood has been separated, it’s stored until it’s needed by hospitals. The red blood cells are stored in a refrigerator and the plasma is frozen. The red cells can be stored for six weeks, and the plasma can be stored for up to a year. Platelets can only be stored for five days. When a hospital needs blood it’s packed into special blood shippers, and transported to the hospital blood bank to be transfused.</p>
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<p><em><strong>Read other articles in the series:</strong></em></p>
<p><em><a href="https://theconversation.com/essays-on-blood-why-do-we-actually-have-it-75064">Essays on blood: why do we actually have it?</a></em></p>
<p><em><a href="http://theconversation.com/from-animal-experiments-to-saving-lives-a-history-of-blood-transfusions-80391">From animal experiments to saving lives: a history of blood transfusions</a></em></p><img src="https://counter.theconversation.com/content/75066/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Denese Marks receives funding from the Australian and New Zealand Society of Blood Transfusion, Defence Health Foundation and MacoPharma Pty Ltd. Australian governments fund the Australian Red Cross Blood Service for the provision of blood, blood products and services to the Australian community.</span></em></p>Blood transports nutrients, hormones, proteins, vitamins and minerals around our body.Denese Marks, Adjunct Associate Professor, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/750642017-07-23T20:10:04Z2017-07-23T20:10:04ZEssays on blood: why do we actually have it?<figure><img src="https://images.theconversation.com/files/178776/original/file-20170719-13561-1ibysp7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We know blood is vital for life, do we know why?</span> <span class="attribution"><span class="source">Illuminations: Blood Equality by Jordan Eagles (USA) Image credit: David Meanix and courtesy of artist as part of Science Gallery Melbourne’s BLOOD exhibition</span></span></figcaption></figure><p><em>This week we’re running a series in collaboration with the Australian Red Cross Blood Service looking at blood: what it actually does, why we need it, and what happens when something goes wrong with the fluid that gives us life. Read other articles in the series <a href="https://theconversation.com/au/topics/blood-series-39533">here</a>.</em></p>
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<p>Just as a village can’t grow into a city without some form of transport (road, rail or river) that provides necessary interconnections for it to flourish, living things are limited in the size they can reach unless they have some form of circulatory system to transport nutrients and remove waste.</p>
<p>Single celled organisms such as bacteria and fungi, and some multicellular creatures such as sponges, corals and flatworms, simply absorb the nutrients they need and get rid of their waste using a passive process known as diffusion (which is much like soaking in and draining out).</p>
<p>More complex animals have developed some kind of circulatory system. A variety of different systems and pumps (hearts) have developed, but they all have a few things in common. These include something to carry oxygen around their bodies, a fluid of some sort, and some “plumbing” – in humans (and a number of other species) the fluid is called blood and the plumbing is our arteries, veins and capillaries. The oxygen carrier is haemoglobin.</p>
<p>Depending on the organism and where it has adapted to live, its oxygen carrier can come in different forms, often giving its “blood” different colours. Spiders, crustaceans, octopuses and squid use haemocyanin, which is based on copper and gives them blue blood. This carrier works well in low oxygen environments and in the cold. </p>
<p>Segmented worms and some leeches use an iron based carrier called chlorocruorin, which can appear either green or red, depending on its chemical environment. Vertebrates, including humans, use haemoglobin, which makes their blood red.</p>
<p>A truly special case is the <a href="https://blogs.scientificamerican.com/brainwaves/how-the-antarctic-icefish-lost-its-red-blood-cells-but-survived-anyway/">Antarctic icefish</a>, which lost its haemoglobin long ago as a result of a presumably random mutation. It has adapted though, and now survives by transporting oxygen that is simply dissolved in its blood. This is possible thanks to the cold conditions it lives in.</p>
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<a href="https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=419&fit=crop&dpr=1 600w, https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=419&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=419&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/176694/original/file-20170704-7743-1u6unbb.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>What is our blood made of?</h2>
<p>Human blood, and that of all creatures with backbones (Antarctic ice fish excepted), is red. The colour comes from a chemical known as haem, which contains iron. It’s the iron that is the crucial ingredient for carrying oxygen. Oxygen is needed for our cells to burn sugars, fats and proteins in a controlled way. This provides us with the energy we need to live.</p>
<p>Outside our bodies, we know that when iron is exposed to oxygen, it rusts. And it doesn’t easily “unrust”. But to work as an oxygen carrier in our bodies, iron needs to “rust” and “unrust” on demand - picking up oxygen where it is in plentiful supply (our lungs), and releasing it where it is required (the cells in our organs).</p>
<p>This on/off oxygen switch is made possible with help from complex larger molecules. The first is haem, a flat ring structure that holds an iron atom at its centre. Haem is held closely by proteins known as globin, and this combination forms haemoglobin, which is itself packaged up in red blood cells to be transported around the body.</p>
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<p><a href="https://theconversation.com/from-animal-experiments-to-saving-lives-a-history-of-blood-transfusions-80391"><em>Infographic - From animal experiments to saving lives: a history of blood transfusions</em></a></p>
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<p>The molecular structure of haemoglobin is delicately tuned to allow it to bind oxygen in the lungs and drop it off in areas where there is less oxygen available.</p>
<p>Red cells are specialised parcels, lacking DNA, that are able to squeeze through the tiniest capillaries, down to four millionths of a meter (equivalent to roughly half their diameter). Their donut shape maximises their surface area to make sure they can efficiently deliver oxygen, while keeping them small enough to fit through the smallest blood vessels.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=286&fit=crop&dpr=1 600w, https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=286&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=286&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=360&fit=crop&dpr=1 754w, https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=360&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/176861/original/file-20170705-4592-1q4j491.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=360&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">The Antarctic ice fish managed to evolve past needing red blood cells and instead absorbs oxygen.</span>
<span class="attribution"><span class="source">Wikimedia Commons</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>More than just the red stuff</h2>
<p>As well as red cells, our blood contains other cells and chemicals that repair and maintain the transport system and send signals around the body.</p>
<p>White blood cells, also known as leukocytes, repel or destroy invaders. Some white blood cells (lymphocytes) manufacture molecules known as antibodies that tag viruses and bacteria for destruction, while others called neutrophils and macrophages (literally “big eaters”) engulf bacteria, fungi and parasites to keep our circulation clean. When neutrophils have done their job you sometimes might see them as the main component of pus.</p>
<p>Platelets are very small fragments of larger cells called megakaryocytes. They react to any breaches to the walls of blood vessels, gathering together and triggering reactions that form a plug (or a clot) for the damaged section. If a person doesn’t have enough platelets, they can suffer from uncontrollable bleeding.</p>
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<span class="attribution"><span class="source">The Conversation</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<h2>Where does it come from?</h2>
<p>All blood cells (red cells, white cells and platelets) develop from haematopoietic (literally meaning “blood-making”) stem cells, located in the bone marrow. It has recently been found that many <a href="https://www.ncbi.nlm.nih.gov/pubmed/28329764">platelets are made in the lungs</a>, from megakaryocytes that have migrated there from the bone marrow.</p>
<p>As stem cells develop, they progressively specialise into the many different types of blood cells, making developmental choices along the way. The specialisation of cells during development is tightly controlled by a symphony of growth factors. In some types of blood cancers and serious diseases, stem cell or bone marrow transplants can be used to “reboot” the blood making system.</p>
<p>As our knowledge of the control of blood cell development grows, we’re making progress towards being able to <a href="https://www.newscientist.com/article/2131517-human-blood-stem-cells-grown-in-the-lab-for-the-first-time/">reproduce this process in cells grown in the laboratory</a>. This is still some time away from being a broadly available process, but an exciting area to watch as it develops.</p>
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<p><em>Update: the sentence outlining the shape of red blood cells was incorrect and has been reworded.</em></p><img src="https://counter.theconversation.com/content/75064/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Irving is employed by the Australian Red Cross Blood Service and has research collaborations with others receiving NHMRC and ARC research grants.
Australian governments fund the Australian Red Cross Blood Service for the provision of blood, blood products and services to the Australian community.</span></em></p>Everything you never knew about the red stuff in your veins.David Irving, Adjunct Professor, University of Technology SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/663782016-10-03T15:29:31Z2016-10-03T15:29:31ZWant to pimp your immune system? Take a holiday<figure><img src="https://images.theconversation.com/files/139989/original/image-20161002-23434-8ynno3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Better than pills.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-338638163/stock-photo-senior-citizen-couple-taking-a-walk-in-a-park-during-autumn-morning.html?src=3-M6uVW-EWQzKIT7fkbHDw-1-11"> IvicDrusany/Shutterstock.com</a></span></figcaption></figure><p>Going on holiday, having a fun night out with friends, or simply relaxing at home with a good book – these activities make us feel good. Now, for the first time, we have evidence that they also do us good. Our latest study shows that our surroundings and lifestyle can have a big impact on our immune system. </p>
<p>We sent lab mice on “holiday” for two weeks. Our <a href="http://journal.frontiersin.org/article/10.3389/fimmu.2016.00381/full?utm_source=FRN&utm_medium=EMAIL_IRIS&utm_campaign=EMI_XIA_161001_Milestones_Author_article_impact_page#">results</a>, published in Frontiers in Immunology, showed that simply housing mice in a cage that is about three times bigger than the standard one and adding toys (an experimental system called “enriched environment”), has a significant impact on their ability to fight infections. Indeed, the T cells of the mice in the enriched environment showed major changes in their genes, with 56 specific genes upregulated (made more active) and four downregulated (made less active). There was also an improved ability to respond to infections and fight pathogens – no drugs, no gene therapies, just two weeks in a more stimulating and engaging environment.</p>
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<h2>Why it matters</h2>
<p>You might ask what this means if we translate it to humans. Well, we all naturally seek more enriched environments and we are empowered with the ability to change place or company when we do not like it. We constantly strive to improve our daily lives and environments. With these new findings, we might feel even more encouraged to do so knowing that it is good for our immune system. </p>
<p>But what about all those who cannot change their environment so easily? What about the growing ageing population that lives in care homes with limited mobility and lower chances of interaction? A seminal study by <a href="https://www.researchgate.net/publication/22550402_Long-Term_Effects_of_a_Control-Relevant_Intervention_with_the_Institutionalized_Aged">Ellen Langer</a> in 1978 showed that just providing nursing home residents with a plant to take care of led to a significant increase in the length of their life. Over an 18-month follow up, those who weren’t given a plant to care for (the control group) were twice as likely to die as those who were given a plant to care for.</p>
<p>The results of our study might help revisit the idea that living conditions have a significant impact on our health. As we grow old, our immune system also grows old and tired. Common flu or infections that are manageable for most of us in our twenties to fifties become life-threatening disease for most elderly. </p>
<p>Is this true only for the old population? Not necessarily. Again, eminent scientists like Donald Winnicott in the 1970s clearly showed the importance of playfulness as an <a href="https://www.amazon.co.uk/Child-Family-Outside-Penguin-Psychology/dp/0140136584">indicator of psychological health</a>. If he were alive today, he would have most certainly have demonstrated the importance of play and fun for the immune system – with or without mice. </p>
<p>I think that we should never wait for someone else to tell us when we need to have a break or have some fun. However, I hope that our work will prompt people to consider that sometimes the cure is not just in the pill.</p><img src="https://counter.theconversation.com/content/66378/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fulvio D'Acquisto receives funding from the Medical Research Council, Arthritis Research UK, the Multiple Sclerosis Society and the British Hearth Foundation. </span></em></p>The first experiment to demonstrate that an enriched environment can boost the function of some immune cells.Fulvio D'Acquisto, Professor of Immunopharmacology, Queen Mary University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/509202015-11-27T04:37:20Z2015-11-27T04:37:20ZAfrica’s answer to 70-year old problem of how to beat repeat infections<figure><img src="https://images.theconversation.com/files/103184/original/image-20151125-23837-xh6v7a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The original antigenic sin has made fighting diseases really difficult.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>Dr Wilfred Ndifon has proposed a <a href="http://rsif.royalsocietypublishing.org/content/12/112/20150627.long">solution</a> to a 70-year old immunological mystery relating to the original antigenic <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023910">sin</a>. This complex problem has played havoc with efforts to fight infectious diseases, particularly in places such as Africa where people can suffer successive infections. Ndifon and Tolullah Oni are two of 12 Next Einstein Forum <a href="http://nef.org/nef-fellows/">Fellows</a> working to solve major challenges in health, education, big data and quantum theory using science, technology, engineering and mathematics.</em></p>
<p><strong>What is the original antigenic sin?</strong></p>
<p>The original antigenic sin was first reported about 70 years ago by American epidemiologist Thomas <a href="http://global.britannica.com/biography/Thomas-Francis-Jr">Francis Jr</a>. But its underlying biological mechanisms are still poorly understood. </p>
<p>This much we know: the human body activates white blood cells to fight an infection. When a new infection comes along the white blood cells are activated again. But they are less effective at fighting the new agent. This makes the body much less able to fight the new disease. This is what Thomas Francis described as the original antigenic sin.</p>
<p>The length of time over which original antigenic sin can occur depends on how long the immune system’s memory of a previous infection lasts, which in turn depends on the infecting pathogen. For pathogens like flu viruses, the immune system’s memory can persist throughout an individual’s lifetime.</p>
<p>The same problem arises when a person is treated with a vaccine to fight pathogen A. When that person is infected by a related pathogen B, the vaccine focuses on pathogen A making it less effective.</p>
<p><strong>Why does this matter?</strong></p>
<p>The original antigenic sin makes fighting diseases really difficult. This is because it reduces the effectiveness of vaccines. This happens because vaccines preferentially reactivate previously activated white blood cells. So past infections increase the risk for more severe future infections and for reduced vaccine effectiveness. </p>
<p>This risk is particularly high in sub-Saharan Africa where infections tend to occur frequently. The risk is high in regions where infections occur frequently simply because you need sequential infections with related pathogens in order for original antigenic sin to manifest.</p>
<p>So, the more infections there are, the more likely it is that the body’s defences will be compromised by original antigenic sin. This is also pertinent in the Northern Hemisphere where there are frequent sequential infections by related variants of flu viruses. This creates an ideal environment for original antigenic sin to manifest.</p>
<p>It is also important in other parts of the world where <a href="http://www.cidrap.umn.edu/news-perspective/2009/08/original-antigenic-sin-threat-h1n1-vaccine-effectiveness">flu</a> is prevalent. </p>
<p>Scientists have documented many instances of the original antigenic sin in humans, mice, and other organisms. </p>
<p>It has been beautifully illustrated in <a href="http://www.jimmunol.org/content/183/5/3294.long">mice</a> that were infected either with only one variant of the flu virus or with that variant followed a month later by another related variant. While the mice infected with only one variant were able to completely control a subsequent infection with that variant, those that were sequentially infected had about 10 000 times more virus in their lungs as a result of original antigenic sin.</p>
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<figcaption><span class="caption">NEF Fellow Wilfred Ndifon on how he solved 70 year old immunological problem.</span></figcaption>
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<p><strong>Can you give a practical example?</strong></p>
<p>Imagine for a minute that you have malaria.</p>
<p>The immune system contains specialised white blood cells that are responsible for protecting the body from pathogens which cause malaria. </p>
<p>When the immune system is exposed to the pathogen, the pathogen is chopped into pieces called antigens. Then it is loaded onto the surface of other white blood cells. The white blood cells then become activated. They are then able to get rid of the malaria. </p>
<p>A small number of these white blood cells remain after the pathogen has been eliminated. They stay behind to enable a swift response to any infection by the same pathogen.</p>
<p>After eliminating malaria, let’s imagine you are infected by a new variant of the pathogen. Normally the body should unleash the same process. But this is not always the case.</p>
<p>In some cases, the white blood cells do not recognise the new pathogen. Instead, they focus on the previous pathogen. An earlier theory suggested that this may result from competition among certain white blood cells called B cells. In immunology this is called the original antigenic sin. </p>
<p><strong>So what’s the solution</strong></p>
<p>My study introduced and confirmed an original theory using mathematics and experimental data. My theory explains why original antigenic sin occurs. It is also the first theory to explain how original antigenic sin can be <a href="http://www.pnas.org/content/109/34/13751.full">alleviated</a> by a substance that is added to a vaccine to better activate the immune system’s cells. What we call an adjuvant.</p>
<p>I show that both original antigenic sin and its alleviation by adjuvants arise from the activity of certain white blood cells called <a href="http://www.nature.com/nri/posters/tregcells/index.html">T</a> regulatory cells.</p>
<p>T regulatory cells activated by previous pathogens weaken certain white blood cells’ ability to load new pathogens onto their surface. This in turn causes fewer white blood cells to become activated, thereby making it difficult for the body to fight new pathogens and leading to original antigenic sin.</p>
<p>But my theory predicts that adjuvants will reduce the inhibition of white blood cell activation that is caused by T regulatory cells, thereby alleviating original antigenic sin.</p>
<p>My discovery opens up additional possibilities for preventing the destructive health consequences of original antigenic sin. For example, it suggests how original antigenic sin can be prevented from reducing a vaccine’s effectiveness. This can be done by designing vaccines so that their components better latch onto the surface of certain white blood cells. </p>
<p>This will counter the effect of the T regulatory cells and make the immune system more effective at getting rid of the pathogens targeted by the vaccine.</p><img src="https://counter.theconversation.com/content/50920/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Wilfred Ndifon receives funding from the Canadian government's International Development Research Centre.</span></em></p><p class="fine-print"><em><span>Tolullah Oni does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Innovative initiative aims to inspire pupils on the continent to take up careers in science.Wilfred Ndifon, Research Chair with joint appointments at both the South African and the Ghanaian centres of the African Institute for Mathematical Sciences. He is also affiliated to the Department of Mathematical Sciences, Stellenbosch UniversityTolullah Oni, Senior Lecturer at the School of Public Health and Family Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.