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    Article 37 - Unleash Your Immunity

    Uploaded by

    Odiljon Muzaffarov

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    © All Rights Reserved
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    Features Cover story IMMUNE SPECIAL Unleash your immunity IMMUNOLOGISTS are making extraordinary progress in their attempts to understand our immune system - the intricate constellation of cells and molecules inside our bodies that defends us against bacteria, viruses, fungi and toxins. Over the next eight pages, we delve into some of the very latest science to find out everything from what foods you should eat to best boost your immune system to why some people never seem to get sick 6INew cents qebrusry 2025 HOW TO TELL WHETHER YOUR IMMUNE. SYSTEM IS HEALTHY OR NOT WHEN youareunder the covers, sniffing from your thied cold ofthe year, youight wonder whether your immune system is pullingits weight. itisa question we would alllove toanswer:isourimmunesystem healthy of not? Now, aburgeoning feld of immunology is attempting todo ust that with tests that “grade” your immunesystem, the dea being that it could help people preempt problemsand motivatethem to ‘make lifestyle changes toavoidill health TTounderstand how healthy yourimmune system realy is let alone improve fist it {shelpfulto get togrips with what tactually does. Considerit your internal army, with diferent units coordinating to eliminate enemy invaders, all whileavoiding collateral damage toyour own tissuesand constantly adapting tonew challenges Uke a realarmy, your immunesystem canalsofallinto disarray, with some units, underperforming while others go rogue. This can cause majorillnesses. Sohow do youtell whether your army Isdoingits best? Let's begin by considering thedifferent components. The ist line of defence comes from innate immune calls such as macrophages, which engulf bacteria and release chemicals that rigger inflammation, makingcells less hospitable to pathogens (see"Get to know your Immunesystem’ page a2). ‘Oncea threat has been identified, a second lineof defence called the adaptive immune system kicks in, with more specialised tools. B-cells forexample, form antibodies that bindto theunwanted neweomerand renderit harmless. T-cells, meanwile, Include ile cells that attack infected cells, aswell ashelpercellsthat coordinate the ‘A bad diet or stress can make you more sluggish at producing the correct immune cells to fight infection” activities ofthe other immune cells and aidthe B-cells in producing antibodies. Regulatory T-cells are also on handtocall off the batle when the threat has passed, sothe body can repair the damage ‘Ourbiological warriors can be found Jurking around the body. "They'reinthe ‘mucosal lining ofour airways, the digestive tract and in ourskin-anywhere things that could upset the body might getin’ says Jenna Macciochi an immunologist at the University ofSussex, UK. They arealso aided by microorganisms {nthebody,knownas the microbiome. “Weoften think bout the microbiome in relation tothe gu, but wehave microbiota livingall over ourbody,”says Macciochi, ‘When weareatpeakhealth, these Afferent components are perfectly balanced ~butthereare waysthat things ‘might go awry. You may lack the friendly microbes that protect your digestive system, ‘meaning you are more susceptibleto gut infections. A bad diet orstress can make you more sluggish at producingthe correct immune cells to ight infection, andafter you have recovered, you mightlose the cells that“remember” the pathogen, should you he exposed again, since the immune system can also spot and remove tumours, underactivity can render yournore susceptible to cancer. ‘Other problemsarise from overactivity, when the immune system begins acting with disproportionate force, leadingittoharm, the body. Forexample,the immunesystem _may become oversensitive to foreign bodies, suchas pollen, that don't pose an actual threat, which leads toallergies. Orit might startattackingits ownorgans, resulting in autoimmune diseases. Even muted immune activity forlong periods oftime, such as Jowe-grade inflammation, canbe harmful and isthought to contribute to everything fiom cardiovascular diseaseto depression, Historically, thereare somebasicwaysto assessthe health of your immune system ~ ‘including, for instance, measuring the levels of inflammatory moleculesand numbers cofimmune cells within your blood. But recently, ourmeasures have become more sophistcated, witha greaterfocuson > 4 February2073|New sents ‘examining the precisebalanceofthe immunesystem’ different components. Sunil Ahuja’s team at the University of Texas Health Science Center forexample, has designed away toclassify people's immune grade” based onthe relative levels of ifferent Fels. People with higherthan- average numbers ofhelper Tcells,combined. ‘with lowerlevelsof killer Ecells,hadthe highest immune grade, aecordingto their classification. The team has shown that people with immune grade tend tohave ‘much beter outcomes when they face ‘apathogen, with 8 percent reduced ‘mortality compared with those oflower trades ater a covid-g infection, for instance Importantly the team’s grades proved to bbea beter predictor forresponsetocovid-9 ‘thanage alone, meaning that inthe future, this kind of messuremay help toidently high-riskindividuals with greater precision (see "How does your immunesystem change asyouage?’ page 43)."Evenifyouate 80, and you have ahigh immune grade, youldo ‘much betterthan someone much younger witha low immune grade” says Abuja Youmay needtowaita whilebefore your doctors ableto assess yourhealth with this kind of precision, but you can get agood ‘dea about thestate of yourimmune system without any tests, Asa general rule fofthumb, Maceiochi saysthat the average person should expect haveone ortwo ‘mild llnessesayear. you tend to become sick far more often, and ifthose infections tend to last much longer and are more severe than the people aroundyou, then it may be aasignthat oneor moreofthe unitsin your {immunearmy aren't functioningasthey should. Your doctor should be your frst por ofcall but thereaealsothingsyoucan oto give your immunity ahelpinghand (see What should youeat boost your immunesystem?’ page a, David Robson Wiitebiood cellscanhelp ‘oindlcate health 8] New Slentit |g February 2025 WHAT EFFECT DID LOCKDOWNS HAVE (ON CHILDREN'S IMMUNE SYSTEMS? ITISa question highin the minds of many parentsand carers ofinfants born during the frst years of the covid-19 pandemic: hhavelockdowns and social distancing hhad along-termeffect on abies’ health? Thegood news sthat these concemsare largely underpinned by misunderstandings ‘over how the mmune system is shaped dduringourfirstyears fli Itisclearthat pandemic public health ‘measures have had an impact on chikren's exposure to bacteria and viruses that cause illness When strict socal distancing rules were in place, thecapacity fr infections tospread was dramatically reduced, ‘Ananaljsis of data from across England foundthat the numberof children below the age of admitted to hospital with influenza between March 2020 and june2021 dropped by ag percent. twasnt ust uthat was alfected: the analysis found reductions inchild hospitalisations in 8 of the19 Infections they ookedat, including mumps, ‘measles, croup, tonslliisand bronchiolts, Fewer infections ‘This eaves lockdown babies in adifferent positiontothe average infant. Typically around goper cent of UK children have had aninfection by the age of, forinstance, but ananalysisofbablesborn during relana’s firstlockdown foundthatlessthanbalfof sa month-oldsexperienced any infections dduringthei first year. Fortunately, wedon't actually need to get sick when weare very young, Infections like fa ate more key toleadtoserious complications, suchas pneumonia in young children, especially those under the age, you can avoid disease, i'sbetterifyou avoidit” say Nikolaos Papadopoulosat the University of Manchester, UK. Inrecent months, thenorthern hemisphere has hada difficult winterin termsof seasonal infections including among children. Lower population immunity ispartlytoblameforsurging levelsofillness caused by pathogens like the fluvirusand RSV: becausetherewere fewer cases ofthese illnesses during trict covid-9 ‘measures, numbers are catchingup now. Thisisn'ta sign that children’simmune systems have heen weakened by lockdown. The idea that itisimportant to get {infections during infancy comes from the hygiene hypothesis, first proposed by epidemiologist David trachan in 1989. ‘Thethinking was tha life had become more hygienic leadingchikdrentocateh fewer ‘infections, andthat this predisposed them. todevelop allergies. But whilethe idea that youngimmunesystemsneed tobe trained’ ‘on pathogens has taken holdin the public consciousness the hygiene hypothesis isn't ‘ourbest vay ofunderstandingimmune systems inthe modern age. What we really reed nearly life isto encountera wide diversity ofmicrobes and not just the ‘ones that arebad for you. ‘The ideal scenario says Papadopoulos, {stobe exposed in very mall quantities tomany different types of microbes, viruses andbacteria below the threshold {or disease" So,ratherthan beinga good ‘thing in tself, getting lis moreofa marker ‘that your child isencountering@ range ‘of microbes, good and bad. Ifyou don't fencounter many pathogens in your first years, that doesn't mean you willbe ess {oodat fighting hem offlateron, because Your immunesystem continues oleam bout diseases throughout ie. However, oureatly years do seemto be important for shaping our response toallergens,anda lackof exposureto diverse microbes uring thistimemay ‘make children more usceptbleto allergies, ‘The number ofehildren hospitalised forsevere infections droppedin 2020-2021 asthma and sometypesof eczema. Thelrish study found that lockdown babies were more likely to have atopiceczema and show signs ofsensitisation to egg~the fist step towards anallergy~although there was no increase inthe proportion of children who actually hada eggallergy by theage of However, thereareotherways we receive early microbial exposure than just socialising Some, suchas being born vaginally rather than by C-section, may not have been affectedby the pandemic. thers, such asbreastfeeding, spending time ‘outside, antibioticuse and even living with pet dog, may have been influenced by the ‘way our lives changed in 2020 and 2021~ positively forsome, negatively for others. ‘Atthesametime, while we know that ll these factors seem to belinked to immune functioning, none of them has strong enough effect tofuly determineyour immune future. twillbe shaped by a complexinterplay of personalcitcumstances, ‘including genetics and many smalland ‘unique differences in the mieroblal environments in which we grow up. Which, ‘thankfully means there sno “right” way totrainayoung immune system, Penny Sarchet| HOW TO TRAIN THE IMMUNE SYSTEM TO CURE SEVERE DISEASE ONE ofthemostamazingthingsabout ‘theimmunesystem is how hard it works ‘without youeven beingaware.I{ not only fights off bacteria and viruses everyday it also kills off most cancerslong before they ‘becomes threat But sometimes cancers ‘manage to dodge the immune system ~ anda numberof cancer therapies ely on restoring iseffectiveness. Anemerging star isCARTcell therapy, which has produced ddramaticresultsforsomecancers when allthe usual treatments have fale. ‘This incredbletechnology relies on ‘eels, mmune ell that patrol our body, lulling infected or eancerouscells. ells detect their targets witha receptor that protrudes from their surface and binds toatarget protein, oradisplayed fragment ofa protein,on the outside ofother cells, ‘What thismeans that fyouaddthe right receptor to Fells, youcan make them target anythingyou want, including cancer ‘Toachievethis,aperson'sown Feels areextracted and genetically modified toexpressa"chimericantigen receptor’ Thisartifcil receptor ismadeupof three proteins, one thatrecognises the cancer cell target andtwothat boost the cells’ activity. Doctors multiply these cellsand return themtotheirowner, wherethey seek out and destroy cll that have the target protein With few ofthe first peopletreated stil remaining free ofcancera decade later, tcan ‘now besaid tha, in some cases, CARTcell ‘therapies can cure advanced cancers Unfortunately, this approach isn'ta magic bullet. Forstarters,theimmuneattackon cancer cellsit promptscan trigger potentially "The average person should expect one or two mild illnesses a year’ {atalside effects. What's more, CAR Tells only workagainst blood cancers, not solid ‘tumours, andonly ina minority of people. ut thereishope. The techniqueisbeing {mproved. One igissueis that havingtouse each individuals own Tells is extremely expensive, and with very ill people, itsn't lays possible to extract enough T-ells Donor‘:cels see every cell nthe recipient's ‘body as foreign and start attackingthem, So, gene editing is now being used to ‘knockout the genes involved in recognising celsas foreign inaddition toadding the receptor. These universal AR'Fcells can. Deusedto teat many different people withthesame cancers Leukaemia success Another issueisthat Feels have an off ‘switch on theirsurfacecalled PD-1tohhelp prevent them attacking healthy cell Some cancers thwart Fell attacks by exploiting this switch But itis removed via gene editing the -cellscan't be deactivated, Withstandard gene editing, there isa limit, tothe number of changes that can be made, This is because each edit requlees cutting DNA,which can illcellsorresult in major ‘mutations. But the latest CRISPR gene: editing tools don’t eut DNAandsoallow _more changes tobe made ately This approach was used last year to ‘reat Fcell leukaemia orthetfirst time. The 13 year-old who recelved the treatment had aggressive leukaemia that hadn't responded toany other therapy. Twenty-eight days Inter, tests revealed she was in remission Other teams reintroducingeven more ambitious changes toCART-cellsin the hopeofmakingthemeffectiveagainst solid tumours too. Theuse of CAR Feels for treating infectionsby pathogens such Aas HIV and hepatitis Cisalso being explored, Furthermore,CART-cellsarebeing usedto ‘reat autoimmune diseasesby killing offthe rogue immune cells responsible. Last year, ‘ateam in Germany reported that five people ‘with lupushave remained fre ofthe disease since being treated this way Genetically engineeredimmune cells aregoing tobeabigpart of ourfuture. isa futurethat looks very bright indeed. Michael LePage “sFebruary20%3[New scientist ‘ARE THERE SEX DIFFERENCES INTHE IMMUNE SYSTEM? ‘THE concept of “man flu"-the dea that men, ‘maketoo big a deal out of coldisanold Joke. But when covidagarrived, wehadto takeaseriouslookat sex differences inhow peoplerespond to infections. Being male was ariskfactor forexperiencing more severe symplomsof the coronaviris:in England during 2020, men were about 6o percent ‘more likely odie from covide19 than women, “Menarealso nearly twice aslikelytobe diagnosed with tuberculosisand slightly ‘more likely to diefrom flu So does your sex putyouat an advantageor disadvantage ‘when it comesto immunity? ‘There may be several reasons for immune sex differences For one thing, we have discovered in recent yearsthat oestrogen, the main female sex hormone, broadly simulates immunesystem activity. The ‘main male equivalent, testosterone, weakens it Butthereare other forces at worktoo, ‘exis governed by DNA, which comes packaged up into23pairsof chromosomes, “Most women have 1woX chromosomes, hile most men have oneX and one. Tomake surethat cellsin female bodies don’t have duplicateX ehromosome {genes in operation, one X is mostly disabled in every cell, Genetic diversity Which chromosometsinactivatedis determined randomly when embryos are afew weeks old Allthe tissues in afernale body ae therefore mosaics, with half theit cells using theX chromosome inherited fromthe mother andtherestusingthe cone fromthe father Because many genes {involved in the immune system are located ‘onthe X chromosome, this means that femalebodies havetwice the genetic variation tocallon when fighting infections. "Women have morediversity whenit comes toindividual enes,’says Shion Moalem, ageneticresearcherbasedin New York, Thaddition, not allthe genes on the inactivated X chromosome are switched of, withsome immunesystem genes remaining functionalon bothX chromosomes~ Including one called oll ike receptor7 (TLR? which helps cells detec viruses. This means that most women have double the dose of 7 intheir immune system. Havinga stronger immune response {sadouble-edged sword, though: may explain why women are more susceptible gol ew Scents] February2029 ‘toautoimmune diseases such as multiple sclerosis and rheumatoidarthits, where the ody starts to recognise its own cells as dangerous andattacks them, Another contributor to this increased risk ‘of autoimmune conditions, could be that ‘the mechanisms o prevent autoimmunity ‘workless wellin female bodies says Moaler, Inthe fetus,immune ces should be “trained” to recognise the body's owncels. Because most Women are mosaics of two popiilations of genetically different cells, ‘this raining process may be less efficent. Ontheother hand, women's greater propensity autoimmunity helps them ‘out when tcomes to cancer which arises ‘when cells start multiplying of contol The immune system isthought todestroy many tumours before they get bigenough tobenoticed see “How totrain theimmune system to cure severe disease’ page 39) Immune cellsthat aren't as welltrained to recognise the body's own cells are more likey to attack them when they start looking different tonormal,as tumour cells do. Therearealsobehaviouralexplanations {orwhy women tend to get fewer cancers ‘than men, sueh as men smoking and drinkingmore~but somuch emphasis hasbeen placed on these socal factors, \wehave previously overlooked the immune sexlferences, says Moslem. “The morewe look, the more wetfind. Clare Wison Being maleis| significant Fiskfactor forsevere covld-19 DO SOME PEOPLE HAVE NATURALLY ‘STRONGER IMMUNE SYSTEMS? \WEALL know that person.The one who rarely getsill The covid-ig pandemic highlighted that when it comes to catching circulating virusesand bacteria, wearen't allequal:some people can resist being {infected by a pathogen even after heavy exposure. Finding out why could help keep the res ofus in better health, ‘A person may resist anillness because they have recently been exposedto the pathogen that causestandthelrbody knows how tofightit off. This wasnt the ceaseforcovid9, sno one had encountered the coronavirus behind itbeforethe end ‘of 2019, ome peopledid seemto have some resistance tot though, due to past {nfections with other, smllar viruses there areat least four coronaviruses that cause ordinary colds. In2021,afew healthcare ‘workers who had nevertested positive for covid-19 despite heavy exposure were ound tohave had “abortive infections” when the virus briefly replicates inside the nose and @ ‘New Scientist audio sap) mewselentist.com/app airway beforebeing wiped out.Theirimmune systems were foundito reacttoan enzyme used by the virus that causes covid-iga well asthecold-causing coronaviruses, People may have resistance to infections ‘because oftheir genetic make-up. For ‘ovid9,this hasbeen investigated in relationto people's riskof dyingfrom or needing respiratory support due otheir Infection. Earlier this year, Johnathan ‘Cooper-Knockat the University of Sheffield, UX, ands colleagues found more than 1300 genetic variants that are responsible forraisingor decreasing an individual’ risk ‘ofdeveloping severe covid-19, Mos affected ‘the unction oftwotypes of immunecell ‘Pcellsand natural killer cells (See "Get to know your immune system’ “The same genevariants may explain ‘why some peopleavoid catching ta al, says Cooper-Knock But now that most people have been vaccinatedagainst ‘covide1g factors that affect how well, people respondto those vaccines may ‘hemoreimportant he says, Other genes may be involved in our susceptibility to different pathogens. bout 1in100 people with European ancestry are nlkely tobe infected by HIV because ofa ‘genetic variant they have, which also affects ‘Teells. Another gene variant thatalects different kindof immune cell called macrophage may alter the likelihood of developing tuberculosis, accordingto a study ‘ofan ethnically diverse sample of US people Given thelr benefits,why doesn'teveryone have immune-boosting genes? Thereason Isthat many geneticvarantscan have both beneficial and harmfulelfects. For instance, ‘one gene variant became more common Inthe British population during the Middle ‘Ages, probably because it boosted the Immuneresponse tothebacterium that ‘caused the Black Death, But last year, it was discovered that this variants now ‘common in people with Crohn's disease. Aswith otherautoimmune conditions, this iscausedby the immune system mistakenly attacking thecells four own body inthis, ‘ase, the els ning the gut “Take this asa warning that while it may seema good thing try to supercharge ‘theimmune system, itis realy balance ‘that matters when it comes to providing ‘the greatest averall protection. ‘Clare Witson WHAT SHOULD YOU EATTO BOOST YOUR IMMUNE SYSTEM? \WALK down any supermarket aisleand you willsee ows offood anddrink that daimto ‘help your immune system, Weare told that ‘innamons good at battling inflammation and ghting off ness forinstance.Thelist ‘of supposedly immune boosting” foods also often includes berries, mushrooms, green tea, seeds, spinach, broccoli, probiotic yogurt and foods high in specific vitamins. ‘The problem sthat when you dig deeper, yousee that most ofthesebold clalmsaren't ‘derived from clinical trials or solid scence. ‘More often than not, they ae based on small, Jabexperiments where chemicalextracts ofthe plants, nuts orherbs re found to alterthe potency ofimmune cells, and these ‘ndings rarely ranslatetoanything useful So, What dowe rally needto-eat to supporta healthy immune response? Only fairly recently have wediscovered that the biggest immune organ isour gut ‘Theimmunesystemis in regular contact ‘with thetrllios of microbes lvingin the gut, which send signals todialimmune activities upor down, “The good newsisthatthedelicate balance ofthissystem canbe modified through let Take chronic low-grade inflammation, Which can bethoughtofasthe result of anoverstimulated immunesystem and FOODS TOMAINTAINA, HEALTHY IMMUNE SYSTEM 1. Fermented foods, suchas imho ket which contain helpful probiotics. 2,Foods china variety of ioe that provide nourishment for beneficial bacteria, suchas leeks, ‘onions, artichokes or cabbage. °3.Foods that dampen any Inflammation after meal, such _as green, leafy vegetables. Artichokes: rich infbre thatfeeds beneficial bacteria, Increases the riskofheart disease and. metabolic problems such as obesity ‘Thecomplexinteractions between the gut ining short chain fatty acids produced. by the fermentation of dietary Nbresby gut ‘microbes, and pro-inflammatory chemicals called cytokinesallcontefbute to our overall levelofinflammation, Eat your veg While anté-inflammatory diets are often promoted in vaguetermsby the nutrition {ndustry, we do know that the composition ofthe gut microbiome can modify chronic {inflammation and that diet has arolein this. Inrecent years, my eamandat King’s College London have been investigating this Link between the microbiomeandour diet ‘nseveral ways. Inthe ist part ofour ZOE PREDICT (Personalized REsponses to etary Composition Trial programme, weasked +3000 people with no known health problems tofillina diet questionnaire and undergo blood tests. People who regularly ate alot ‘of vogetabes had lower levels of circulating White blood cells. This resultedin lower levelsofchronicinflammation anda lower Tiskof chronicdiseases ‘Thispositiveimpact of vegetables could be duet their high concentration of fibreand compounds called polyphenol, which act as, prebiotics for our gut microbes, promoting ‘the growth and activity of beneficial bacteria, ‘healthy balance of gut microbesalso seems tobe helped by eating fermented foods such as miso, kombucha and kimehi ‘These contain liverncrobes that can {ncrease your gut microbiome diversity Strongevidencesupportingspectic types of fermented foods above othersis slillunavailable However, we now know thatthe microbes frommany fermented products make i past ourstomach to our colon wherebactera reside, Although they only stay forashort whiletheydohave > «a February2oz3[New sents a. “Immune-boosting foods are simply gut-friendly foods” timeto stimulate the production ofhelpfl chemicals thataid our metabolism. Forthe gut microbes o work optimally in supporting our immunehealth, we need ‘acombination ofegular probiotics ~the bacteria themselves ~plusa variety of good prebiotic foods for the mictobesto ferment Into helpful chemicals forus Foods toavoid are thosethat contain litle ornofibreandause rapid spikes in blood glucose levels as wells prolonged highblood fa levels after meals. hese are associated with post-meal inflammation ‘that can become chronicwith repeated intake of sugary foods. Highly refined carbs and.ultra-processed foods especialy those that contaln cheap processed meats are the biggest culprits. Arficial sweeteners and ‘emulsifierscan also harm your gut microbes. ‘My take-home messageis that the gut microbiomeand our diets are closely linked, and oth factors interact with ourimmune system incomplex ways. “immune boosting" foods, therefore, are simply {gutfrendly foods: looking after your diet helps your gut mirobesto help yourimmuinesystem doitsjob, (CAN WECREATE AN ARTIFICIAL IMMUNE SYSTEM? (ONEofthe most important features of the immune system isthattcan lear and remember, kindof biological intelligence that srivalledonly by the brain. And just like the brain, researchers are attempting toreplicatethisinteligence atficially. by

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