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11.1A: Selle en organe van die immuunstelsel - Biologie

11.1A: Selle en organe van die immuunstelsel - Biologie


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Die immuunstelsel sluit primêre limfoïede organe, sekondêre limfatiese weefsels en verskeie selle in die aangebore en aanpasbare immuunstelsels in.

Leerdoelwitte

  • Herken die selle en organe van die immuunstelsel en hul funksies

Kern punte

  • Die belangrikste primêre limfoïede organe van die immuunstelsel is die timus en beenmurg, en sekondêre limfweefsels soos milt, mangels, limfvate, limfknope, adenoïede en vel en lewer.
  • Leukosiete (witbloedselle) tree op soos onafhanklike, eensellige organismes en is die tweede arm van die aangebore immuunstelsel.
  • Die aangebore leukosiete sluit in die fagosiete (makrofage, neutrofiele en dendritiese selle), mastselle, eosinofiele, basofiele en natuurlike moordenaarselle. Hierdie selle identifiseer en elimineer patogene en is ook belangrike bemiddelaars in die aktivering van die aanpasbare immuunstelsel.
  • Die selle van die aanpasbare immuunstelsel is spesiale tipes leukosiete, wat limfosiete genoem word. B -selle en T -selle is die belangrikste tipes limfosiete en is afgelei van hematopoietiese stamselle in die beenmurg.
  • Die limfatiese stelsel is 'n deel van die bloedsomloopstelsel, wat bestaan ​​uit 'n netwerk van buise wat limfatiese vate genoem word. Die limfstelsel het verskeie funksies, soos die vervoer van witbloedselle na en van die limfknope na die bene.

Sleutel terme

  • limfosiete: 'N Limfosiet is 'n tipe witbloedsel in die gewerwelde immuunstelsel. Die drie hooftipes limfosiete is T -selle, B -selle en natuurlike moordenaarselle (NK). T-selle (timuselle) en B-selle (bursa-afgeleide selle) is die belangrikste sellulêre komponente van die adaptiewe immuunrespons.
  • Leukosiete: Selle van die immuunstelsel betrokke by die verdediging van die liggaam teen beide aansteeklike siektes en vreemde materiale. Vyf verskillende en diverse tipes leukosiete bestaan.

Immuunstelsel organe

Die belangrikste primêre limfoïede organe van die immuunstelsel sluit in die timus en beenmurg, sowel as sekondêre limfweefsels, insluitend milt, mangels, limfvate, limfknope, adenoïede, vel en lewer.

Die timus "voed" T-selle op en verskaf 'n induktiewe omgewing vir die ontwikkeling van T-selle uit hematopoietiese stamvaderselle. Die timus is die grootste en aktiefste gedurende die neonatale en pre-adolessente periodes van ontwikkeling. Teen die vroeë tienerjare begin die timus atrofeer en word thymiese stroma vervang deur vetweefsel. Tog bly die oorblywende T-limfopoese gedurende die volwasse lewe voort.

Beenmurg is die buigsame weefsel wat in die binnekant van bene voorkom. By mense word rooibloedselle in die koppe van lang bene geproduseer. Die rooi beenmurg is 'n belangrike element van die limfstelsel, een van die primêre limfoïede organe wat limfosiete genereer uit onvolwasse hematopoietiese stamvader selle. Beenmurg en timus vorm die primêre limfoïede weefsels wat betrokke is by die produksie en vroeë seleksie van limfosiete.

Die limfatiese stelsel is 'n deel van die bloedsomloopstelsel, wat bestaan ​​uit 'n netwerk van buise genaamd limfatiese vate wat 'n helder vloeistof, genoem limf, eenrigting na die hart dra. Die limfstelsel het verskeie onderling verwante funksies, insluitend die vervoer van witbloedselle na en van die limfknope na die bene, en die vervoer van antigeen -teenwoordige selle (soos dendritiese selle) na die limfkliere waar 'n immuunrespons gestimuleer word. Limfoïede weefsel word in baie organe aangetref, veral die limfknope.

Die milt is in struktuur soortgelyk aan 'n groot limfknoop en dien hoofsaaklik as 'n bloedfilter. Dit sintetiseer teenliggaampies in sy wit pulp en verwyder teenliggaampies bedekte bakterieë saam met teenliggaampies bedekte bloedselle deur middel van bloed- en limfknope.

Die palatien mangels en die nasofaryngeale mangel is limfoepiteelweefsels wat naby die orofarynx en nasopharynx geleë is. Hierdie immuunkompetente weefsels is die immuunstelsel se eerste verdedigingslinie teen ingeneemde of ingeasemde vreemde patogene. Die fundamentele immunologiese rolle van mangels word nog nie verstaan ​​nie.

Limfknope word wyd versprei oor dele van die liggaam, insluitend die oksel en maag, en verbind deur limfvate. Limfknope is garnisoene van B, T en ander immuunselle. Limfkliere dien as filters of strikke vir vreemde deeltjies en is belangrik vir die behoorlike werking van die immuunstelsel. Hulle is styf verpak met die witbloedselle, wat limfosiete en makrofage genoem word.

Die vel is een van die belangrikste dele van die liggaam, omdat dit in kontak is met die omgewing en die eerste verdedigingslinie teen eksterne faktore is, wat dien as 'n anatomiese versperring van patogene en skade tussen die interne en eksterne omgewing in liggaamlike verdediging. Langerhans -selle in die vel vorm deel van die aanpasbare immuunstelsel.

Die lewer het 'n wye verskeidenheid funksies, insluitend immunologiese effekte - die retikulo -endotheelstelsel van die lewer bevat baie immunologies aktiewe selle, wat dien as 'n 'sif' vir antigene wat via die portaalstelsel na dit vervoer word.

Immuunstelsel selle

Leukosiete (witbloedselle) is immuunstelselselle wat betrokke is by die verdediging van die liggaam teen aansteeklike siektes en vreemde stowwe. Daar bestaan ​​vyf verskillende soorte leukosiete, wat almal geproduseer en afgelei is van 'n veelpotige sel in die beenmurg wat bekend staan ​​as 'n hematopoietiese stamsel. Die aangebore leukosiete sluit die fagosiete, mastselle, eosinofiele, basofiele en natuurlike doderselle in. Hierdie selle identifiseer en elimineer patogene en is belangrike bemiddelaars in die aktivering van die aanpasbare immuunstelsel.

Neutrofiele en makrofage is fagosiete wat deur die liggaam beweeg om patogene binne te dring. Neutrofiele word normaalweg in die bloedstroom aangetref en is die algemeenste tipe fagosiet. Tydens die akute fase van inflammasie migreer neutrofiele na die plek van inflammasie en is gewoonlik die eerste selle wat by die infeksietoneel aankom. Makrofage woon binne weefsels en produseer 'n wye verskeidenheid chemikalieë. Hulle tree ook op as aasdiere en verwyder die liggaam van verslete selle en ander puin, en as antigeen-aanbiedende selle wat die adaptiewe immuunstelsel aktiveer. Dendritiese selle is fagosiete in weefsels wat in kontak is met die eksterne omgewing, en is hoofsaaklik in die vel, neus, longe, maag en ingewande geleë. Hierdie selle dien as 'n skakel tussen die liggaamsweefsels en die aangebore en aanpasbare immuunstelsels, aangesien hulle antigeen aan T-selle aanbied, een van die sleutelseltipes van die aanpasbare immuunstelsel.

Mastselle woon in bindweefsels en slymvliese, en reguleer die inflammatoriese reaksie. Dit word meestal geassosieer met allergie en anafilakse.

Basofiele en eosinofiele is verwant aan neutrofiele. Hulle skei chemiese bemiddelaars af wat betrokke is by die verdediging teen parasiete, en speel 'n rol in allergiese reaksies, soos asma.

Natuurlike doderselle is leukosiete wat tumorselle aanval en vernietig, of selle wat deur virusse besmet is.

Die selle van die adaptiewe immuunstelsel is spesiale tipes leukosiete, wat limfosiete genoem word. B -selle en T -selle is die belangrikste tipes limfosiete en is afgelei van hematopoietiese stamselle in die beenmurg.

T-selle herken 'n 'nie-self'-teiken, soos 'n patogeen, eers nadat antigene verwerk en aangebied is in kombinasie met 'n' self'-reseptor, 'n belangrike histokompatibiliteitskompleks (MHC) molekule genoem. Daar is twee hoofsubtipes van T-selle: die moordende T-sel, wat selle doodmaak wat met virusse (en ander patogene) besmet is of andersins beskadig of disfunksioneel is, en die helper T-sel, wat beide aangebore en aanpasbare immuunresponse reguleer en help bepaal watter immuunreaksies die liggaam op 'n bepaalde patogeen maak. Hierdie selle het geen sitotoksiese aktiwiteit nie en maak nie besmette selle dood of maak patogene direk skoon nie. 'N Derde, geringe subtipe is die γ T -selle wat ongeskonde antigene herken wat nie aan MHC -reseptore gebind is nie.

In teenstelling hiermee is die B-sel-antigeenspesifieke reseptor 'n teenliggaammolekule op die B-seloppervlak, wat hele patogene herken sonder dat antigeenverwerking nodig is. Elke geslag van B -sel druk 'n ander teenliggaam uit, sodat die volledige stel B -sel -antigeenreseptore al die teenliggaampies verteenwoordig wat die liggaam kan vervaardig.


Androgeen- en androgeenreseptore as reguleerders van monosiet- en makrofaagbiologie in die gesonde en siek long

Androgene, die oorheersende manlike geslagshormone, dryf die ontwikkeling en instandhouding van manlike eienskappe aan deur aan die androgeenreseptor (AR) te bind. Aangesien androgene sistemies deur die hele organisme versprei word, beïnvloed dit baie weefsels en seltipes benewens dié in manlike geslagsorgane. Dit is nou duidelik dat die immuunstelsel 'n teiken is vir androgeenwerking. In die longe spreek baie immuunselle AR uit en reageer hulle op androgeen. In hierdie oorsig beskryf ons die uitwerking van androgene en AR's op long-myeloïede immuunselle-monosiete en makrofage-soos dit verband hou met gesondheid en siekte. In die besonder beklemtoon ons die effek van androgene op longsiektes, soos asma, chroniese obstruktiewe longsiekte en longfibrose. Ons bespreek ook die terapeutiese gebruik van androgeen en hoe sirkulerende androgeen met longsiekte korreleer. Benewens menslike studies, bespreek ons ​​ook hoe muismodelle gehelp het om die effek van androgene op monosiete en makrofage in longsiekte te ontbloot. Alhoewel die rol van estrogeen en ander vroulike hormone breedvoerig in die literatuur ontleed is, fokus ons op die nuwe perspektiewe van androgeen as modulators van die immuunstelsel wat myeloïede selle teiken tydens longontsteking.

Sleutelwoorde: androgeen androgeen reseptor asma long makrofag monosiet geslagsverskil geslagshormoon.

Kopiereg © 2020 Becerra-Diaz, Song en Heller.

Syfers

Geslagsverskille in longsiektes ...

Geslagsverskille in longsiektes wat in hierdie oorsig bespreek word en hoe dit kan ...

Die uitwerking van androgene op ...

Die effekte van androgene op muis- en menslike monosiete en makrofage in vitro…


'N Vinnige opsomming van die immuunstelsel en die COVID-19-entstof

Daar is baie strategieë vir die ontwikkeling van 'n entstof, maar die idee agter almal is soortgelyk. Entstowwe is ontwerp om 'n vreemde indringer, soos 'n virus of bakterie, aan te pas by u aanpasbare immuunstelsel sonder dat u siek word. Ons immuunstelsels is ongelooflik, wat dit ook baie ingewikkeld maak. Hier fokus ons op 'n paar aspekte wat belangrik is om die ontwikkeling van entstowwe te verstaan.

Entstowwe gee ons immuunstelsel 'n sjabloon, waaruit ons liggame immuun 'geheue' kan bou teen 'n spesifieke patogeen (bv. Virus of bakterie). As ons dan weer deur hierdie patogeen geïnfekteer word, sal hierdie immuungeheue die simptome wat ons ervaar verminder. Beeldkrediet: CC0 op Pixabay.

Entstowwe bevat tipies 'n deel van 'n patogeen (bv. virus of bakterie) en stimuleer die produksie van teenliggaampies teen hierdie patogeen. Inentings 'maak' ons immuunstelsel 'goed' om beter voorbereid te wees op 'n infeksie as ons weer aan die patogeen blootgestel word. Beeldkrediet: CC0 op Pixabay.

Twee hooftipes selle herken siektes in ons immuunstelsel, spoel dit uit en bou 'geheue' vir ons immuniteit teen latere invalle: B-selle en T-selle. Hierdie adaptiewe immuunsel tipes kan onafhanklik of saam werk om infeksie te beveg en geheue te bou teen her blootstelling aan die indringer (bv. Die virus, bakterie, parasiet, kankersel, ens.). T -selle het die vermoë om hierdie indringers direk dood te maak, ander immuunstelsel selle te werf na die plek van infeksie en te help met die ontwikkeling van B -selle. Hulle kan ook geheue verleen deur die vrystelling van proteïene wat sitokiene genoem word. B-selle stel Y-vormige proteïene vry wat teenliggaampies genoem word, wat op soortgelyke wyse indringers herken en werk om hulle te vernietig. Wanneer iets vreemds ons liggame binnedring, begin B-selle teenliggaampies teen daardie indringer skep. Alhoewel hierdie selle ongelooflik goed is om ons liggame teen infeksie te beskerm, neem hierdie proses tyd (ongeveer 7 dae vir die aanpasbare immuunstelsel). As ons immuunstelsel egter met 'n spesifieke indringer 'aangevul' is, kan dit baie vinnig teenliggaampies teen hierdie indringer produseer as dit weer daaraan blootgestel word, wat herinfeksie voorkom. Die gebruik van entstowwe gee ons immuunstelsel (insluitend ons B- en T-selle) 'n sjabloon om immuungeheue teen herinfeksie te ontwikkel sonder om die volle simptome van virale blootstelling te ervaar.

So, hoe lok entstowwe ons immuunstelsel om 'n verdediging teen virusinfeksies te bied? Daar is baie verskillende tipes entstowwe, maar hulle gebruik almal dele van die virus om ons immuunstelsel te mislei om teenliggaampies teen die virus te skep, wat ons immuunstelsel effektief 'gereed maak' om gereed te wees om vinnig teenliggaampies te genereer wanneer ons aan die werklike virus blootgestel word. Soos jy jou kan voorstel, is daar baie verskillende dele van 'n virus om van te kies wanneer entstowwe geskep word, en sommige virusse is moeiliker om 'n entstof teen ander te ontwikkel. Virusse soos griep kan vinnig muteer, en daarom het ons elke jaar 'n nuwe griepinspuiting nodig om ons teen die mees algemene griep-stam te beskerm. Trouens, baie RNA-virusse kan vinnig muteer, wat nuwe stamme skep wat dalk 'n ander entstof benodig om doeltreffend te wees. Koronavirusse, soos COVID-19, is RNA-virusse (lees meer oor die nuwe koronavirus hier).

Die Moderna en Pfizer-entstowwe bevat messenger-RNA (mRNA) wat vir een van die proteïene van COVID-19 kodeer. Hierdie 'stuk' COVID-19 veroorsaak nie 'n infeksie nie, maar verbeter die immuunstelsel se vermoë om COVID-19 te herken en teenliggaampies daarteen te skep, as ons daaraan blootgestel word. Beeldkrediet: CC0 op Pixabay.

Daar is tans baie verskillende tipes entstowwe wat ontwikkel word vir COVID-19, waarvan drie goedgekeur is vir noodgebruik in die VSA Hierdie pos fokus op die twee entstowwe wat deur Moderna en Pfizer gemaak word, wat mRNA-entstowwe genoem word. Vir die huiwerige mense wat besef dat dit 'n nuwe tipe entstof is, is dit belangrik om daarop te let dat hierdie tipe entstof deur meer as 10 jaar navorsing ondersteun word. mRNA, of boodskapper-RNA, is saamgestel uit genetiese kode vir die sintetisering van proteïene. Die sellulêre masjiene in ons liggame lees mRNA en gebruik dit om die proteïene in ons selle te bou. Virale proteïene word ook gemaak deur dieselfde masjiene wat ons selle gebruik. 'N MRNA -entstof vir die nuwe koronavirus bevat dus mRNA wat vir een van die virus se proteïene kodeer. Sodra iemand die entstof toegedien het, word die mRNA in die entstof opgeneem, deur ons selle gesintetiseer en aan die adaptiewe immuunstelsel voorgelê om dit te 'priem', net soos die adaptiewe immuunstelsel na 'n natuurlike infeksie toegedien sou word. B-selle het dan die vermoë om die vreemde indringers te herken en teenliggaampies daarteen te skep sodat die proteïen verwyder kan word. Aangesien ons B-selle 'n herinnering het aan wanneer en as ons aan COVID-19 blootgestel word, kan ons liggaam dit herken en 'n immuunrespons vinniger opbou, wat veroorsaak dat dit ons stelsel skoonmaak voordat dit tyd het om ons te besmet. Dit is belangrik om in gedagte te hou dat hierdie proteïen nie 'n aansteeklike virus is nie, maar eerder 'n deel van die virus as 'n geheel. Daarom kan mRNA-entstowwe nie 'n infeksie veroorsaak nie. As u meer wil leer oor mRNA -entstowwe, lees hierdie blogpos hier.

Met drie entstowwe wat nou beskikbaar is vir noodgebruik, behoort ons binnekort 'n lig aan die einde van die pandemiese tonnel te sien. Om uit te vind wie tans in aanmerking kom vir inenting in die staat Indiana, kyk hier! Soos altyd, bly veilig en bly op hoogte!


Nuwe bevindinge dui daarop dat orgaanweefsel deur die hele lewe toenemend immuun word

MINNEAPOLIS/ST.PAUL (20/04/2021) - Navorsers van die Universiteit van Minnesota se mediese skool bied nuwe maniere om na te dink oor die immuunstelsel danksy 'n onlangse studie wat in Natuur. Hulle navorsing, wat daarop dui dat orgaanweefsels lewenslank toenemend immuun word, kan begin om die fundamentele idees rakende die inentingsreëls en die funksie van die immuunstelsel binne die liggaam te verander.

Saythi Wijeyesinghe, PhD, die hoofskrywer van die studie is 'n navorser in die Masopust Lab by die U of M Mediese Skool, wat fokus op T-sel-immuniteit. Sy navorsing het begin met die doel om die lewensduur van T -selle in orgaanweefsels te verstaan, waarvan bekend is dat dit virusse afweer, terwyl dit ook beskerm word teen herinfeksie deur dieselfde virus.

"Histories het studies van die immuunstelsel die hernubare aard daarvan beklemtoon deur beenmurg, limfoïede organe en bloed. Ons werk wys hoeveel hierdie model nie rekening hou met die baie immuunselle wat deur ander organe van die liggaam versprei word, waar die meeste infeksies en gewasse ontstaan,” het Wijeyesinghe gesê. "Wat ons gevind het, skets uiteindelik 'n baie breër prentjie van hoe die immuunstelsel toesig oor die hele liggaam vir patogene, weefselskade en gewasse bewerkstellig."

Die belangrikste bevindinge van die studie sluit in:

    - Antivirale T-selle wat in die meeste organe van die liggaam woon, bly oor tyd en te midde van uitgebreide aansteeklike blootstelling

- Anders as ander orgaanstelsels, word die immuunstelsel lewenslank toenemend immuunstelsel, wat mettertyd 'n natuurlike reaksie is op opgehoopte mikrobiese blootstelling

- Tot 25% van die selle in organe was immuunselle, wat aandui dat die immuunstelsel aansienlik bydra tot die sellulêre samestelling van die liggaam

- En saam met antivirale T-selle is die meeste ander immuunselle ook duursaam in weefsels.

Wijeyesinghe hoop dat hierdie studie die deurlopende verandering in die wyse waarop die breër wetenskaplike gemeenskap die immuunstelsel en immuunhomeostase kan konseptualiseer, verder kan bevorder.

Tydens hierdie studie het Wijeyesinghe ook onverwags ontdek hoe weefsel-inwonende T-selle kan dien as die oorsprong vir geheue T-selle in bloed. As 'n volgende stap in hierdie navorsing ontwikkel die Masopust Lab nuwe tegnieke om die lot van hierdie immuunselle op te spoor, in die hoop om die verband tussen bloedgedraagde en weefselgebaseerde immuniteit verder te ontleed.

Hierdie studie word befonds deur die University of Minnesota Medical School, die National Institutes of Health -toelaes (R01 AI084913, R01 AI146032, F30 DK114942 en T32 AI007313) en Howard Hughes Medical Institute Faculty Scholars -program.

Oor die Universiteit van Minnesota Mediese Skool

Die Universiteit van Minnesota Mediese Skool is aan die voorpunt van leer en ontdekking, die transformasie van mediese sorg en die opvoeding van die volgende generasie dokters. Ons gegradueerdes en fakulteite produseer hoë-impak biomediese navorsing en bevorder die praktyk van medisyne. Besoek med.umn.edu om te leer hoe die Universiteit van Minnesota alle aspekte van medisyne vernuwe.

Vrywaring: AAAS en EurekAlert! is nie verantwoordelik vir die akkuraatheid van nuusberigte wat op EurekAlert geplaas word nie! deur bydraende instellings of vir die gebruik van enige inligting deur die EurekAlert-stelsel.


Ontdekking van die immuunstelsel kan chroniese orgaanverwerping beëindig

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Die tempo van akute verwerping binne 'n jaar nadat 'n oorplanting aansienlik afgeneem het, maar baie mense wat 'n orgaanoorplanting kry, benodig waarskynlik 'n tweede een in hul leeftyd weens chroniese verwerping, het Fadi Lakkis, besturende direkteur van Frank & amp, gesê. Athena Sarris leerstoel in oorplantingsbiologie en is wetenskaplike direkteur van Pitt & rsquos Thomas E. Starzl Transplantation Institute. Die ontbrekende skakel op die gebied van orgaanoorplanting is 'n spesifieke manier om verwerping te voorkom, en hierdie bevinding bring ons 'n stap nader aan die doel. & rdquo

Die navorsers het toe molekulêre en genetiese ontledings gebruik om te wys dat 'n molekule genaamd gepaarde Ig-agtige reseptor-A (PIR-A) nodig was vir hierdie herkenning en geheue kenmerk van die aangebore immuunselle in die gashere. Toe PIR-A óf geblokkeer is met 'n sinteties vervaardigde proteïen of geneties uit die gasheerdier verwyder is, is die geheue-reaksie uitgeskakel, sodat oorgeplante weefsels nog baie langer kon oorleef.

BEELDINLIGTING: (klik elkeen vir weergawes met hoë resolusie)

Byskrif: grafiek wat die oorlewingsyfers van transplantaat vir nieroorplantings in 1985 en 2016 vergelyk: Mediese vooruitgang het gehelp om die tempo van akute afstoting dramaties te verlaag (binne die eerste jaar) na oorplanting, maar chroniese afstoting verminder steeds die oorlewing op lang termyn van die orgaan.

KREDIET: Fadi Lakkis, Universiteit van Pittsburgh, data aangepas uit die Amerikaanse Renal Data System


11.1A: Selle en organe van die immuunstelsel - Biologie

Uiters nuttige kursus om die basis te verstaan ​​van wat immunologie is! Ek beveel dit absoluut aan! en dankie aan die instrukteur, sy was baie maklik om te verstaan ​​en kon my verloof hou!

Die kursus bied 'n uitstekende, stap-vir-stap gedetailleerde uiteensetting van immuniteit vanuit die stelselbiologie-perspektief: begin op organismevlak en daal na die sel- en molekulêre vlakke.

Преподаватели

Alma Moon Novotny, Ph.D.

Текст видео

Voordat ons gaan kyk na die spesifieke selle wat by immuniteit betrokke is, gaan ons begin en kyk hoe ons in die eerste plek by hulle uitkom. Dit wil sê, ons kyk na die bron van dit alles hematopoiese. Soos dit blyk, herstel u voortdurend al u bloedselle, en interessant genoeg, is daar 'n hematopoietiese stamsel wat u kan veroorsaak. U kan sien dat dit nie eens die moontlike bloedsoorte dek nie. hier onder. Maar dit is waar hulle vandaan kom. As ons dus na 'n hematopoietiese stamsel kyk, kyk ons ​​na iets wat 'n pluripotente stamsel genoem word, dit wil sê dat dit 'n baie moontlike ontwikkelingsfase het. As dit net tot een seltipe aanleiding kon gee, sou dit 'n stamsel van 'n bepaalde soort wees. As dit 'n stamsel was soos in die vroeë embrio's, sou dit as totipotent beskou word omdat dit tot enigiets kan lei. Maar jy kan sien dat hierdie spesifieke stamsel 'n hele klomp verskillende opsies het, maar almal is tipes bloedselle. Hierdie stamsel word eers goed gevorm voordat jy gebore word, as 'n embrio in die dooiersakmembraan wat afgelei is van die werklike membraan wat voedsel uit die eiergeel in amniot -eiers haal en eintlik 'n vestigiale struktuur is, behalwe die hematopoietiese stamsel generasie by soogdiere. Nou, hierdie selle, migreer hulle vinnig na die lewer en milt namate die embrio ontwikkel, en teen die tyd dat u gebore is, het u 'n populasie van hulle in u beenmurg gevestig. Hierdie ouens is regtig merkwaardig. As ek eintlik so min as 50 of 100 van hierdie selle oorplant, bedoel ek jy kan hulle van een persoon na 'n ander tel, hulle kan die hele bloedselpopulasie van 'n individu herskep. Dit het 'n paar merkwaardige moontlikhede vir beenmurgoorplantings, outoloë beenmurgoorplantings. Hulle kan goeie selle uit u verwyder, al die slegte mense doodmaak, dit weer inbring, u bloedselle herstel met iets gesond. Dit kan baie van die probleme wat mense met oorplanting versus gasheer siekte het, omseil. Maar dit kan nogal 'n uitdaging wees om dit te versamel. Ons sal sien dat sodra hematopoietiese stamsel begin differensieer, en ons hier noodlottig sal word, dit oppervlakmolekules sal begin plaas op die oppervlak wat sal sê dat dit deel uitmaak van 'n afstamming en dit sal dit nie voorheen hê nie . Maar tog is daar so min hiervan dat dit regtig 'n uitdaging is om dit uit te haal. Dus, ons gaan voort om te kyk hoe hierdie sel u volledige bloedtoevoer lewer. Voordat ons daarnatoe gaan, is ek bang dat sommige van u dalk bagasie van die junior hoërskool af saamneem, en dit wil sê dat ek op skool 'n primitiewe manier gehad het om bloedselle te beskryf en te kategoriseer . Dit wil sê, ons het eritrosiete gehad, dit is die rooibloedselle en die bloedplaatjies en dan witbloedselle wat al hierdie ander tipes insluit en dan 'n paar. So, hier is 'n herinnering. Rooibloedselle of eritrosiete maak die meerderheid van die selle in die bloedstroom uit, maar hulle is 'n baie spesifieke gevolg van hematopoiese, hulle is in die myeloïede afkoms wat ons sal sien. Hulle het 'n bietjie samewerking met die immuunstelsel, maar basies is hulle daar om suurstoftoevoer en ph in jou bloed te handhaaf. Die bloedplaatjies hier is klein fragmente uit selle, en ons kan sien dat ons begin met megakaryosiete wat deur 'n ontwikkelingsfase gaan en hierdie klein bloedplaatjies wat soms trombosiete genoem word, afknyp. Weereens, hierdie dinge sal eintlik help om die immuunstelsel te stimuleer, maar trombosiete word nie as deel van die witbloedselle beskou nie. Megakariosiete aan die ander kant is witbloedselle, en hier op die foto het ons 'n metaforiese megakariosiet wat getoon word as 'n openbare werke-verdediger en hier het ons 'n gat in jou bloedvat. Hierdie ou gaan die lek toestop soos enige goeie instandhoudingswerker. U kan natuurlik sien dat hierdie man dit doen met bloedplaatjies wat hy in klein verlengstukke van sy sitoplasma afknyp en die bloedplaatjies op hierdie gat gaan bars en help om dit aan te sluit. Boonop het ons ook hierdie reseptor hierbo, wat 'n trombopoletienreseptor is, gewys, en as u baie skade in u stelsel opdoen, ontvang hierdie ouens boodskappe wat sê dat u in gevaar is en dat hulle reguleer hul produksie van bloedplaatjies. Dus, om nie te meegevoer te raak met al hierdie dinge nie, maar net om jou te herinner dat wanneer jy begin met 'n hematopoietiese stamsel, dit 'n reeks seine sal moet ontwikkel om in die een of ander pad te gaan. En hier het ons een aan die bokant en daar is basies twee verskillende besluite wat dit kan maak, en dit is om 'n hematopoietiese stamsel te bly en voort te gaan om te verdeel en te regenereer. En die transkripsiefaktor BMI-1 is belangrik in daardie besluit. As u egter ekstra selle in u bloedstroom benodig, en dit is 'n konstante en voortdurende behoefte, sal sommige van die selle wat hematopoietiese stamselle is, die transkripsiefaktor GATA-2 ontkoppel, en die GATA-2 sal hierdie ouens begin stuur. ontwikkelingspaaie na spesifieke funksionele self. Een van die eerste dinge wat blykbaar gebeur, is dat hulle iets in hul oppervlaktes sit, Lin, vir afstamming, en dit sal dus afstamming plus selle wees, terwyl die hematopoietiese selle afstammelinge minus of lin minus sal wees. Nou, die eerste besluit wat hierdie sel moet neem nadat dit besluit het om iewers heen te gaan, is of hy deel moet wees van die limfoïede of myeloïede geslag. Dus, as dit deel van die limfoïede afkoms gaan word, sal dit 'n ander transkripsiefaktor, Ikaros, spesifiek opreguleer, en as dit nie die geval is nie, het dit eintlik 'n verskeidenheid transkripsiefaktore wat standaard is, maar baie ingewikkeld is . Dit sal lei tot die myeloïde afstamming. Dus, as jy hier agterkom, het ons 'n gemeenskaplike myeloïde stamvader en 'n gemeenskaplike limfoïede stamvader. Die gewone myeloïde stamvader produseer 'n groot klomp selle, insluitend megakaryosiete, bloedplaatjies, eritrosiete en 'n klomp ander selle wat ek gaan beskryf en beskryf. Die Ikaros sal dit na die algemene limfoïede stamvader stuur wat ander dendritiese selle maar ook NK-selle produseer en dan die adaptiewe selle wat hul geen herrangskik, wat in B-selle en T-selle sal kom. Teen die tyd dat ons by T -selle kom wat ons na hierdie volgende een sal doen, begin ons spesifieke seine in die selmembraan sien, en dit is in die kerffamilie van seine wat vir 'n verskeidenheid gebruik word ontwikkelingsgebeurtenisse vanaf ons voorwortel. Dit is 'n algemene beeld van hoe ons dit kry, en in die volgende afdeling gaan ons na die myeloïede selle kyk.


Limfosiete --- Hart van die immuunstelsel

Hoe limfosiete antigene herken

Wanneer 'n antigeen die liggaam binnedring, neem gewoonlik net daardie limfosiete met reseptore wat by die kontoere van daardie spesifieke antigeen pas deel aan die immuunrespons. Wanneer hulle dit doen, word sogenaamde dogterselle gegenereer wat reseptore het wat identies is aan dié wat op die oorspronklike limfosiete gevind word. Die resultaat is 'n familie limfosiete, wat 'n limfosietkloon genoem word. met identiese antigeenspesifieke reseptore.

'n Kloon gaan voort om te groei nadat limfosiete die eerste keer 'n antigeen teëgekom het sodat, as dieselfde tipe antigeen die liggaam 'n tweede keer binnedring, daar baie meer limfosiete spesifiek vir daardie antigeen gereed sal wees om die indringer te ontmoet. Dit is 'n belangrike komponent van immunologiese geheue .

Hoe limfosiete gemaak word

Sommige limfosiete word in die beenmurg verwerk en migreer dan na ander dele van die liggaam-spesifiek die limfoïede organe (sien Limfstelsel). Hierdie limfosiete word B-limfosiete genoem, of B-selle (vir selle wat afkomstig is van beenmurg). Ander limfosiete beweeg uit die beenmurg en word verwerk in die timus, 'n piramide-vormige limfoïede orgaan wat onmiddellik onder die borsbeen op die vlak van die hart geleë is. Hierdie limfosiete word T-limfosiete, of T-selle (vir timus-afgeleide selle) genoem.

Hierdie twee soorte limfosiete --- selle en T-selle --- speel verskillende rolle in die immuunrespons, alhoewel hulle saam kan optree en mekaar se funksies kan beïnvloed. Die deel van die immuunrespons wat B-selle betrek, word dikwels humorale immuniteit genoem omdat dit in die liggaamsvloeistowwe plaasvind. Die deel wat T -selle behels, word sellulêre immuniteit genoem omdat dit direk tussen die T -selle en die antigene plaasvind. Hierdie onderskeid is egter misleidend, want streng gesproke is alle aanpasbare immuunresponse sellulêr --- dit wil sê hulle word almal geïnisieer deur selle (die limfosiete) wat op antigene reageer. B -selle kan 'n immuunrespons inisieer, maar die sneller antigene word eintlik uitgeskakel deur oplosbare produkte wat die B-selle in die bloed en ander liggaamsvloeistowwe vrystel. Hierdie produkte word teenliggaampies genoem en behoort aan 'n spesiale groep bloedproteïene wat immunoglobuliene genoem word. (sien "T -selle"), na 'n groter sel wat 'n ontploffingsel genoem word. Die ontploffingsel begin vinnig verdeel en vorm 'n kloon van identiese selle.

Sommige hiervan verander verder in plasmaselle --- in wese, teenliggaamproduserende faktone. Hierdie plasmaselle produseer 'n enkele tipe antigeen-spesifieke teenliggaampie teen 'n tempo van ongeveer 2 000 teenliggaampies per sekonde. Die teenliggaampies sirkuleer dan deur die liggaamsvloeistowwe en val die sneller-antigeen aan.

Teenliggaampies val antigene aan deur daaraan te bind. Sommige teenliggaampies heg hulself aan indringende mikroörganismes en maak hulle onbeweeglik of verhoed dat hulle liggaamselle binnedring. In ander gevalle werk die teenliggaampies saam met 'n groep bloedproteïene, wat gesamentlik die komplementstelsel genoem word, wat uit ten minste 30 verskillende komponente bestaan. In sulke gevalle bedek teenliggaampies die antigeen en maak dit onderhewig aan 'n chemiese kettingreaksie met die komplementproteïene. Die komplementreaksie kan die indringer laat bars, of kan aasselle lok wat die indringer "eet".

Not all of the cells from the clone formed from the original B cell transform into antibody-producing plasma cells some serve as so-called memory cells. These closely resemble the original B cell, but they can respond more quickly to a second invasion by the same antigen than can the original cell. T -selle. There are two major classes of T cells produced in the thymus: helper T cells and cytotoxic, or killer, T cells. Helper T cells secrete molecules called interleukins (abbreviated IL) that promote the growth of both B and T cells. The interleukins that are secreted by lymphocytes are also called lymphokines. The interleukins that are secreted by other kinds of blood cells called monocytes and macrophages are called monokines. Some ten different interleukins are known: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, interferon, lymphotoxin, and tumor necrosis factor. Each interleukin has complex biological effects.

Cytotoxic T cells destroy cells infected with viruses and other pathogens and may also destroy cancerous cells. Cytotoxic T cells are also called suppressor lymphocytes because they regulate immune responses by suppressing the function of helper cells so that the immune svstem is active onlv when necessary.

The receptors of T cells are different from those of B cells because they are "trained" to recognize fragments of antigens that have been combined with a set of molecules found on the surfaces of all the body's cells. These molecules are called MHC molecules (for major histocompatibility complex). As T cells circulate through the body, they scan the surfaces of body cells for the presence of foreign antigens that have been picked up by the MHC molecules. This function is sometimes called immune surveillance.


Crosstalk between microbiota and extra-intestinal organ immunity

Although most studies in the field to date focused on the interplay of microbiota and mucosal immunity in the intestine, interactions of both the gut microbiota and extra-intestinal microbiota communities with extra-intestinal organ immunity have been gaining increased attention (Fig. 3). Emerging evidence highlights that the local microbiomes of extra-intestinal mucosal surfaces provide niche-specific functions, including modulation of organ-specific immune responses.

The gut microbiome and microbiome-associated metabolites translocate from the intestinal lumen to various organs (e.g., liver, brain or lung) through the circulatory system, and subsequently induce tissue-specific local immune responses. In the liver, bacterial LPS is recognized by TLR4 in different cell types, leading to upregulation of various pro-inflammatory chemokines and adhesion molecules. MAMPs influence the number, function and maturation of Kupffer cells, and glycolipid antigen-containing probiotics can activate hepatic NKT cells. The gut-resident pathobiont Klebsiella pneumoniae can translocate and induce Th17 cell responses in the liver. In the CNS, microbiome-derived SCFAs regulate microglial homeostasis, and promote regulatory T cells to counter-regulate CNS autoimmunity. In the lung, SCFA-induced primed myeloid cells translocate to the lung and shape the pulmonary immunological landscape. Clostridium orbiscindens-derived product desaminotyrosine modulates type I IFN signaling. In addition, exposure to different lung-resident microbes (e.g., Pseudomonas, Lactobacillus, pneumotypeSPT) is associated with an enhanced Th17 type response.

Alike the intestine, the skin (the body’s largest organ) represents a dynamic and complex ecosystem, harboring and interacting with a plethora of locally-entrenched commensal microorganisms. High throughput sequencing-based studies revealed a diversity of site-specific but temporally stable microbial communities in the healthy human skin 200,201 featuring inter-individual variability. 202 The skin microbiota induces protective and regulatory immunity that contributes to host-microbe mutualism. Skin-resident commensals not only effectively control the equilibrium of T effector and regulatory T cells in the tissue, dependent of IL-1 and MyD88 signaling, 111 but also regulate components of the cutaneous complement system 203 as well as the expression of various cutaneous AMPs. 204 Certain aspects of the regulation of cutaneous innate and adaptive immunity by the skin microbiome feature strain specificity. One of the most highly abundant skin commensals, Staphylococcus epidermidis, can specifically induce homing of CD8 + T cells primed by CD103 + DCs into the epidermis and can promote skin antimicrobial responses in an IL17-dependent manner. 205 Furthermore, the S. epidermidis-specific CD8 + T cell response is restricted to non-classical MHC class I molecules, which also promote tissue repair. 206 During skin injury,TLR2 recognition of S. epidermidis cell wall component lipoteichoic acid suppresses skin inflammation and inhibits release of inflammatory cytokines, thereby promoting wound healing. 207 It should be noted that colonization with skin commensal during the neonatal period is crucial for establishing immune tolerance through massive accumulation of active T regulatory cells in the neonatal skin, collaboratively driven by hair follicle morphogenesis. 208,209 Moreover, epidermal keratinocytes also actively participate in cutaneous immune defenses. Microbial metabolites, such as SCFAs produced by the commensal skin bacterium Propionibacterium acnes, can modulate keratinocyte inflammatory activity through inhibition of the keratinocytes’ histone deacetylases. 210 Furthermore, cutaneous commensals such as coagulase-negative Staphylococcus strains produce antimicrobials that protect from pathobionts such as Staphylococcus aureus. 211

Skin dysbiosis has been associated with different inflammatory skin disorders, including atopic dermatitis 212 and psoriasis. 213 Whether skin dysbiosis is the cause or consequence of these disorders is not yet clarified, but it has been proposed that locally amplified immune responses to particular skin microbes, or increased microbial load, in the setting of impaired skin barrier and genetic predisposition, might contribute to pathology. 214 For example, skin colonization with Staphylococcus aureus promotes skin allergy in a mouse model of atopic dermatitis through δ-Toxin-induced mast cell activation. 215 Furthermore, epidermal JunB is critical for immune-microbiota interactions, as mice lacking JunB expression in skin epithelial cells are characterized by augmented Th2 and Th17 type immune responses, accompanied by increased S. aureus colonization. 216 However, many open questions remain to be explored, including the molecular basis of cutaneous microbiota-immune interactions and mechanisms by which the cutaneous immune system discriminates between skin commensals and pathogens.

Emerging evidence highlights an important crosstalk between the gut microbiome and the lung (‘gut-lung axis’). Alterations in the gut microbiome or microbiome-derived metabolites may impact on lung immunity in the context of pulmonary diseases. Gut commensals regulate antiviral immunity at the respiratory mucosa through inflammasome activation upon influenza A virus infection. 217 Accordingly, GF mice show an impaired pulmonary pathogen clearance. 218 Microbiome-derived SCFAs promote bone marrow hematopoiesis, and the primed myeloid cells subsequently migrate to the lung, shaping the lung’s immunological landscape and conferring protection against airway inflammation. 219 Desaminotyrosine, a product derived from the gut commensal Clostridium orbiscindens, exerts distal effects on the lung to protect against influenza through modulation of type I IFN signaling. 220

Additionally, recent evidence points towards a potential of a locally entrenched lung microbiota possibly impacting pulmonary immunity. 221 In mice, the rapid formation of an airway microbiome within the first 2 postnatal weeks is critical for immune tolerance to inhaled allergens through PD-L1-related mechanisms. 222 The human microbiome in the lower respiratory tract forms within the first 2 postnatal months, alongside lung immune maturation. 223 Alterations of the lung microbiota has been implicated in exacerbation of chronic pulmonary diseases, including chronic obstructive pulmonary disease, asthma and cystic fibrosis. 224 Notably, exposure to different lung microbes is associated with different cellular immune responses. For example, enrichment of Pseudomonas en Lactobacillus in mouse models of chronic lung inflammation, 225 or pneumotypeSPT derived from a diseased human bronchoalveolar system, 226 is related to an enhanced Th17 type response. Pathobionts such as members of Proteobacteria induce severe TLR2-independent airway inflammation and lung immunopathology. 227 More recent evidence suggests that certain lung commensals may instigate the development of pulmonary adenocarcinoma by activating γδ T cells that produce IL17. This highlights the putative role of a lung microbiome-immunity crosstalk in lung cancer. 228 However, the study of the lung microbiome and the interplay between commensal microbial communities and pulmonary immunity is only in its infancy, with many more mechanistic insights expected to be revealed in future studies.

Liver

The liver features direct anatomical connection to the gastrointestinal tract via the portal venous circulation and bile duct system, thereby being constantly exposed to bacterial products of gut microbiome origin (‘gut-liver axis’). Intestinal commensals and their products were repeatedly reported to translocate from the intestinal lumen to the liver in certain contexts, in which they may impact hepatic immune responses. For example, microbial-associated molecular patterns (MAMPs) from gut bacteria can directly influence the number, function and maturation of hepatic Kupffer cells (KCs), a critical componentof the hepatic innate immune system. 229 Intestinal pathogens may exacerbate immunological hepatic injury by activating DCs and NKT cells in the liver. 230 Similarly, glycolipid antigen-containing probiotics were reported to stimulate hepatic NKT cells in a strain- and dose-dependent manner. 231 Hepatic stellate cells, the main fibrosis-inducing cell line in the liver, can also be directly stimulated by bacterial lipopolysaccharide (LPS), mainly through induction of TLR4 signaling. This results in an upregulation of multiple chemokines and adhesion molecules. 232 Innate immune sensing of gut-derived microbial products by different TLRs, including TLR4, TLR9, TLR5, and their downstream impacts on liver inflammation in the context of NAFLD/NASH have been recently reviewed elsewhere. 180

Liver inflammation impacted by gut microbiota was also described in primary sclerosing cholangitis (PSC), a chronic inflammatory and cholestatic liver disease. The enteric pathobiont Klebsiella pneumonia cultured from PSC patient specimens was demonstrated to damage the intestinal epithelial barrier, thereby inducing bacterial translocation that promotes Th17 cell responses in the murine liver. 233 Interestingly, a recent study showed alterations of the bile microbiota in PSC patients, characterized by reduced biodiversity, higher abundance of the pathobiont Enterococcus faecalis, and increased levels of the noxious secondary bile acid taurolithocholic acid. 234 However, it remains unclear whether these alterations are causally involved in PSC or are merely a consequence of biliary disease.

Recent studies also demonstrated carcinogenic effects of microbiome-derived small molecules via regulation of immune responses in liver malignancy, including secondary bile acid mediating upregulation of hepatic NKT cells, 189 deoxycholic acid modulating the inflammatory secretome, 235 lipoteichoic acid regulating prostaglandin E2 expression, 236 and LPS signaling through TLR4. 237

Central nervous system

The development of a healthy brain and balanced neuro-immunity relies on integration of numerous endogenous and environmental cues. Among these, molecular signals originating from the gut microbiome may play prominent roles in modulating brain cell function. 238 Microglia are among the primary innate immune cells in the CNS, and are instrumental in CNS immune defense and contribute to brain development and homeostasis. 239 The microbiota contributes to microglia homeostasis, potentially mediated by signaling through SCFAs. 240 GF mice display marked defects in microglia structure and function and hence feature impaired CNS innate immune responses. 240,241 Interestingly, the maternal microbiome impacts on microglial development during prenatal stages, and microglial perturbations associated with the absence of microbiota manifest in a sex-dimorphic manner. 242 Both microbial dysbiosis and microglial dysfunction have been described in several neurological diseases, including behavioral, inflammatory and neurodegenerative disorders. 243 Whether microbiota-microglia interactions contribute to the pathogenesis of these disorders merits further studies.

Moreover, diet-derived SCFAs were reported to promote regulatory T cells to counter-regulate autoimmunity in the CNS, 139 and the intestinal microbiota modulates meningeal IL-17 + γδ T cells, which impact on the pathogenesis of ischemic brain injury. 244 Despite tremendous recent advances, the study of the interplay between the microbiome and neuro-immunity in health and disease is still in its infancy. Some studies shed light on possible mechanisms driving such putative 'gut-brain axis' in the context of neuro-immunity. For example, depletion of gut commensal bacteria by antibiotic treatment dampens the progression of experimental autoimmune encephalomyelitis in mice, which is suggested to be mediated by induction of IL-10-producing regulatory T cells. 245 Offsprings of pregnant female mice that harbor certain gut bacteria with a propensity to induce T helper 17 response are at increased risk of developing neurodevelopmental disorders. 246 Interestingly in a murine maternal immune activation model, IL-17a-mediated inflammatory responses were shown to exert beneficial roles in improving social behaviors in offsprings of adult mice. 247 Potential microbiota involvement in these mechanisms merits further studies. Continued research efforts in this direction may hold great therapeutic promise in uncovering new regulatory pathways impacting a variety of inflammatory, developmental and degenerative neurological diseases.

Intra-organ low-biomass microbiomes

There is growing recent interest in utilizing next-generation sequencing to characterize sparsely populated low-biomass microbiomes in seemingly ‘sterile’ organs, such as the skin, 206 lungs, 248 reproductive organs 249 and bile ducts. 234 However, caution is required in interpreting such findings, as many studies that attempt to investigate low-biomass microbiome samples are challenged by high false positive signals resulting from contamination and sequencing-related challenges and artefacts. 250 Contaminating microbial DNA may originate from multiple environmental sources, such as laboratory extraction, amplification and library preparation kits. 251 Notably, the notion of the existence of a placental microbiome and its link to reproductive health was recently challenged by a thorough comparison of results using different kits, blank controls and complementary approaches of microbial detection not exclusively relying on sequencing. 252,253 In order to avoid fallacious conclusions, strategies to control contamination must be considered when working with low microbial biomass tissues, including experimental and computational measures. 250,254,255,256 Although promising, these strategies largely still await proof that signals uncovered from low-biomass microbiomes reliably translate into verifiable mechanistic biological insights.


When the Immune System Fails

Unless you're shot in the head or hit by a bus, your immune system has a major and direct influence on your life span!

Under normal circumstances the immune system acts for the good of the host - preventing infection and cancer. However, it can sometimes seem to be acting in a negative manner by actually causing disease rather than preventing it. This article aims to discuss and highlight two extremes of the immune system, with disease examples for both.

The Goldilocks phenomenon

Disorders in an individual's immune system can result in conditions of varying severity from affecting quality of life through to death. Often described as the "Goldilocks phenomenon", the activity of the immune system can result in disorders through either not reacting readily enough or by eliciting an immune response too promptly. In the first instance, where the immune system is not responsive enough, immunodeficiency diseases can occur, often resulting in recurring and life-threatening infections

Immunodeficiency can arise from a number of sources the result of a genetic disease, such as in the case of severe combined immunodeficiency (SCID) from the use of pharmaceuticals, such as immunosuppressive drugs or through an infection, such as acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. In situations when the immune system is hyperactive and works more effectively than it should, the result can be an attack on normal tissues, as if they were foreign organisms. This can result in autoimmune diseases such as diabetes mellitus (type I diabetes), rheumatoid arthritis, lupus erythematosus, coeliac disease and allergies to name but a few.

Immunodeficiency can occur when one or more components of the immune system are defective or inactive. The ability of the immune system to respond to pathogens is reduced in both the very young and the elderly, with immune responses starting to decline after the age of 50 on average due to immunosenescence. In developed countries obesity, alcohol consumption and drug abuse are common causes of poor immune function. However, malnutrition is the most common cause of immunodeficiency globally due to the often poor diet of individuals in developing countries. Diets lacking sufficient protein and deficiency of single nutrients such as iron, copper, zinc, selenium, vitamins A, C, E, and B6, and folic acid have all been reported to reduce immune responses. Additionally, loss of thymus function at an early age through genetic mutation or surgical removal, for example during some paediatric heart surgery, can result in severe immunodeficiency. Immunodeficiency can also be inherited, for example chronic granulomatous disease (CGD) is a genetic condition whereby patients suffer from recurrent bouts of infection due to the decreased capacity of their immune system's phagocytes to fight off disease-causing pathogens. HIV infection and some types of cancer result in acquired immunodeficiency as a symptom.

Overactive immune responses

In contrast, an overactive immune system can be the cause of several conditions characterised by an inappropriate response by the immune system. This can be down to either a failure to fully distinguish between self and non-self, thus resulting in an attack on the body's own tissues as in the case of autoimmunity, or by an over-reaction to the environment in the instance of hypersensitivity. These undesirable and damaging responses may be divided into four classes based on the mechanisms involved and the timeframe of the reaction:

TikBeskrywingExample
ekAn immediate or anaphylactic reaction, often associated with an allergy. Symptoms range from mild discomfort to death.Asma
IIOccurs when antibodies bind to antigenson the patient's own cells, marking them for destruction,Autoimmune haemolytic anaemia
IIITriggered by aggregations of antigens, complement proteins and antibodies which are deposited in various tissues.Sistemiese lupus eritematose
IVAlso known as cell-mediated or delayed type hypersensitivity, these conditions usually take between two and three days to develop and are involved in many autoimmune and infectious diseases. May also involve contact dermatitis as in the case of poison ivy.Contact dermatitis

Immunodeficiency case study

Severe combined immunodeficiency (SCID), or Boy in the Bubble Syndrome, is a severe, genetically inherited immunodeficiency disorder in which one's adaptive immune system is completely disabled due to a defect in one of several genes. SCID is listed as a rare disease by the Office of Rare Diseases of the National Institutes of Health, meaning that SCID, or a subtype of SCID, affects less than 200 000 people in the US population. Affected individuals are extremely vulnerable to infectious diseases with symptoms including chronic diarrhoea, ear infections, recurrent pneumonia and profuse oral infection with Candida. Babies born with SCID, if untreated, usually die within their first year due to severe, recurrent infections. Several US states are undergoing pilot studies to diagnose SCID in newborns (as of February 1st 2009 Wisconsin and Massachusetts screen all newborns). To date, the most common treatment for SCID is a bone marrow transplant from a related donor, preferably in the first 3 months after birth or before the child is born. Gene therapy techniques have also been developed and as a result, the first treatment of SCID patients occurred in 2000 and allowed these individuals to have a functional immune system for the first time. These trials are, however, on hold due to an increased occurrence of leukemia in these patients.

Hypersensitivity case study

Asthma is a very common chronic disease the affects the respiratory system whereby the airways constrict, become inflamed and lined with excess mucus. Often in response to one or more triggers, an asthmatic response may result from exposure to airborne allergens, tobacco smoke, cold or warm air, perfume, exercise, stress to name but a few. Symptoms of asthma can range from mild to life-threatening and include wheezing, chest tightness and itching, coughing and shortness of breath. Such symptoms can usually be controlled with a combination of drugs and environmental changes following the identification of triggers. Attention in developed countries has focused on asthma because of its rapidly increasing prevalence, affecting up to one in four urban children. However, asthma is caused by complex interactions of environmental and genetic factors that are not yet fully understood. By the end of 2005 25 genes had been associated with asthma in several populations. Many of these genes are related to the immune system or to modulating inflammation.

Autoimmune case study

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disorder, the causes of which are still incompletely known. It most commonly results in the inflammation and tissue damage of joints and tendon sheaths. RA can be a disabling and painful condition which can ultimately lead to the substantial loss of function and mobility. Whilst there is currently no known cure for RA, treatment can alleviate symptoms and in some cases modify the process. Such treatments range from physical therapy, painkillers and anti-inflammatory drugs through to disease-modifying antirheumatic drugs (DMARDs) which can be used to inhibit the causative immune processes. The course of RA varies greatly with some people having mild short-term symptoms but, in most cases the disease is progressive and chronic.


11.1A: Cells and Organs of the Immune System - Biology

  • body's ability to resist or eliminate potentially harmful foreign materials or abnormal cells
  • consists of following activities:
    • Defense against invading pathogens (viruses & bacteria)
    • Removal of 'worn-out' cells (e.g., old RBCs) & tissue debris (e.g., from injury or disease)
    • Identification & destruction of abnormal or mutant cells (primary defense against cancer)
    • Rejection of 'foreign' cells (e.g., organ transplant)
    • Inappropriate responses:
      • Allergies - response to normally harmless substances
      • Autoimmune diseases
      • Bacteria - induce tissue damage & produce disease largely by releasing enzymes or toxins that physically injure or functionally disrupt affected cells & organs
      • Viruses - can only reproduce in host cells & cause cellular damage or death by:
        • depleting essential cellular components
        • causing cellular production of substances toxic to cell
        • transforming normal cells into cancer cells
        • inducing destruction of cells because infected cell no longer recognized as 'normal-self' cell


        The innate immune response functions as the first line of defence against infection. It consists of soluble factors, such as complement proteins, and diverse cellular components including granulocytes (basophils, eosinophils and neutrophils), mast cells, macrophages, dendritic cells and natural killer cells. The adaptive immune response is slower to develop, but manifests as increased antigenic specificity and memory. It consists of antibodies, B cells, and CD4 + and CD8 + T lymphocytes. Natural killer T cells and gamma-delta T cells are cytotoxic lymphocytes that straddle the interface of innate and adaptive immunity (Dranoff 2004). Dendritic cells are leucocytes that get their name from their surface projections that resemble the dendrites of neurons. They are found in most tissues of the body and are particularly abundant in those that are interfaces between the external and internal environments, e.g., skin and the lining of the gastrointestinal tract. Dencritic cells present antigen/self-antigen complexes that activate T-cells. Gamma-delta cells are primarily found in the intestine, the lining of the vagina, and the skin. They encounter antigens at those locations and, therefore, serve as a first line of defense.



        Nonspecific Immune Responses

        2 - Interferon - group of proteins that defend against viral infection

        3 - Natural killer cells - lymphocyte-like cells that rather nonspecifically lyse & destroy virus-infected cells & cancer cells

        • can be caused by microbial infections, physical agents (e.g., trauma, ultraviolet radiation, burns, or 'frostbite'), & tissue necrosis resulting from inadequate blood flow
        • principle effects include:
          • Redness - inflamed tissue appears red, e.g., skin affected by sunburn, due to dilation of small blood vessels within the damaged area
          • Heat - an increase in temperature is seen in peripheral parts of the body, such as the skin. It is due to increased blood flow to the area as a result of vascular dilation and the delivery of warm blood to the area.
          • Swelling - results from edema (accumulation of fluid in the extra vascular space)
          • Pain - results partly from the stretching and distortion of tissues due to edema and, in particular, from pus under pressure


          Bacterial invasion or tissue damage

          Arterial vasodilation & Increased capillary permeability

          Increased blood flow to tissue & accumulation of fluid


          http://www.biologymad.com/Immunology/inflammation.jpg


          Immunology in the gut mucosa

          • family of similar proteins
          • interfere with replication of the same or unrelated viruses in other host cells
          • Mechanism:

          Interferon binds with receptors on uninvaded cells

          Uninvaded cells produce enzymes capable of breaking down viral mRNA

          Virus enters previously-uninvaded cell (now with interferon)

          Virus-blocking enzymes are activated

          Virus unable to multiply in newly invaded cells


          Interferon and the immune response

          • lymphocyte-like cells
          • destroy virus-infected cells & cancer cells by lysing their membranes upon first exposure
          • mode of action similar to cytotoxic T cells (but latter can attack only cells to which they have been previously exposed)
          • an important first line of defense against newly arising malignant cells and cells infected with viruses, bacteria, and protozoa. They form a distinct group of lymphocytes with no immunological memory. Natural Killer Cells constitute 5 to 16 percent of the total lymphocyte population. Their specific function is to kill infected and cancerous cells.
          • activated by invading organisms &, more often, triggered by antibodies ('complements' action of antibodies)
          • consists of 11 plasma proteins produced by liver


          The complement cascade after activation by pathogens. Tthe complement cascade is usually activated by antibody complexes (classical pathway). This activation leads opsonization and phagocytosis, as well as lysis as a result of the formation of the membrane attack complex (MAC). These combined actions of complement lead to the elimination of pathogenic cells (Figure modified from Ricklin and Lambris 2007).
          • Functions: 1 - Membrane-attack complex proteins form a channel in membrane of invading cell. The resulting influx of water causes lysis (or bursting) of the invading cell.


          Complement system (more detailed!)

          The complement system consists of a series of proteins that work to "complement" the work of antibodies in destroying bacteria.

          • Selective attack aimed at "target" following prior exposure
          • Two classes of responses:
            • Humoral immunity - antibodies produced by B lymphocytes
            • Cell-mediated immunity - activated T lymphocytes


            Lymphocytes originate as stem cells in the bone marrow.
            Some migrate to the Thymus & develop into T-cells others remain in the bone marrow & develop into B-cells.
            Both B- & T-cells then migrate to lymphoid tissue.


            Organs and tissues of the immune system
            (www.niaid.nih.gov)


            B lymphocytes (or B cells) are most effective against bacteria & their toxins plus a few viruses, while T lymphocytes (or T cells) recognize & destroy body cells gone awry, including virus-infected cells & cancer cells.


            Clonal selection (and expansion of the vertebrate immune response (Figure from Bergstrom and Antia 2006)

            The adaptive immune response of vertebrates works by clonal selection. Independent of exposure to an antigen or pathogen, the immune system generates a repertoire of immune cell lineages or clones (labeled 1&ndash8 in the above Figure), each encoding a receptor with a predetermined shape and specificity. The human immune system creates in excess of 10,000,000 different clones. As a first approximation, those that react with self-antigens (numbers 3, 5, and 8 in Figure I) are deleted shortly after they mature. When the individual is infected with a pathogen, those clones that are specific for the pathogen (number 2 in the above Figure) will proliferate, producing a pathogen-specific immune cell population that is large enough to control that pathogen. This process is known as clonal expansion. After the pathogen is cleared, some of the pathogen-specific immune cells survive and confer immune memory (Bergstrom and Antia 2006).

            • Antigen = foreign protein (e.g., an antigenic protein from the outer surface of the Lyme disease bacterium is pictured to the right)
            • Each B & T cell has receptors on surface for binding with a particular antigen.
            • B-cells that bind with an antigen will subsequently differentiate into Plasma cells & Memory cells
              • Plasma cells - begin to produce antibodies (up to 2,000 per second)
              • Memory cells - remain dormant until a person is again exposed to the same antigen

              The B cell uses its receptor to bind a matching antigen, which it proceeds to engulf and process. Then it combines a fragment of antigen with its special marker, the class II protein. This combination of antigen and marker is recognized and bound by a T cell carrying a matching receptor. The binding activates the T cell, which then releases lymphokines interleukins that transform the B cell into an antibody- secreting plasma cell.

              • Grouped into 5 subclasses:
                • IgM - B cell surface receptor for antigen attachment secreted early in an immune response
                • IgG - most abundant antibody produced in large numbers



                Source: NIAID

                  • IgA - found in secretions of digestive, respiratory, urinary, & reproductive systems, as well as in breast milk and in tears
                  • IgD - found on the surface of many B cells function is unknown (but may play a role in activation of B cells)


                  Source: Check (2007).

                  IgA -- a doublet -- concentrates in body fluids such as tears, saliva, and the secretions of the respiratory and gastrointestinal tracts. It is, thus, in a position to guard the entrances to the body.

                  • provide protection by:

                  2 - agglutination (see example to the right)

                  • activation of complement system
                  • enhancement of phagocytosis
                  • stimulation of killer cells


                  The different biological effects of antibodies (Casadevall et al. 2004).

                  Plasma cells vs. Memory cells


                  (a) Development of memory B cells and plasma cells.
                  (b)
                  Development of memory T cells. After activation, cells differentiate into effector T cells and effector memory T cells (Gray 2002).
                  • prolific producers of customized antibodies (IgG antibodies)
                  • have lots of ROUGH ENDOPLASMIC RETICULUM (RER) because antibodies are proteins & RER is needed to make proteins (because of the associated ribosomes) and then transport them out of the cell
                  • formation and subsequent production of takes several days after exposure to an antigen & peak antibody production may occur a week or two after exposure. This is referred to as the PRIMARY RESPONSE.
                  • remain dormant but respond quickly if exposed to the antigen a second time
                  • responsible for SECONDARY RESPONSE, a response so fast & effective that infection is typically prevented.
                  • form the basis for long-term immunity


                  Primary response vs. Secondary response:

                  • Active ('natural') = production of antibodies as a result of exposure to an antigen (immunization)
                  • Passive = direct transfer of antibodies formed by another person (or animal), e.g., transfer of IgG antibodies from mother to fetus across placenta or in colostrum ('first milk') OR treatment for rabies or snake venom

                  Infants are born with relatively weak immune responses. They have, however, a natural "passive" immunity they are protected during the first months of life by means of antibodies they receive from their mothers. The antibody IgG, which travels across the placenta, makes them immune to the same microbes to which their mothers are immune. Children who are nursed also receive IgA from breast milk it protects the digestive tract. Passive immunity can also be conveyed by antibody-containing serum obtained from individuals who are immune to a specific infectious agent. Immune serum globulin or "gamma globulin" is sometimes given to protect travelers to countries where hepatitis is widespread. Passive immunity typically lasts only a few weeks.

                  "Active" immunity (mounting an immune response) can be triggered by both infection and vaccination. Vaccines contain microorganisms that have been altered so they will produce an immune response but will not be able to induce full-blown disease. Some vaccines are made from microbes that have been killed. Others use microbes that have been changed slightly so they can no longer produce infection. They may, for instance, be unable to multiply. Some vaccines are made from a live virus that has been weakened, or attenuated, by growing it for many cycles in animals or cell cultures.

                  • defend against invaders that 'hide out' inside cells (where antibodies & complement system cannot reach them)
                  • must be in direct contact with their targets
                  • activated by foreign antigen only when present on surface of cell that also has "self-antigens" (except whole transplanted foreign cells)
                  • Three types of T cells:
                    • Cytotoxic (killer) T cells - destroy host cells bearing foreign antigen (e.g., host cells invaded by viruses and cancer cells)
                    • Helper T cells - enhance development of B cells into antibody-secreting cells & enhance activity of cytotoxic & suppressor T cells
                    • Suppressor (or Regulatory) T cells - suppress B cell antibody production & cytotoxic & helper T cell activity effects are primarily the result of chemicals called CYTOKINES (or LYMPHOKINES)
                    • Most frequently target host cells infected with viruses
                    • Release PERFORIN molecules to destroy target cells --> PERFORIN molecules form channels in target cell membrane & inrush of water lyses cell


                    Figure slightly modified from Iwasaki and Medzhitov 2010


                    Cytotoxic T cell attacking cancer cell

                    • "Activation" requires MACROPHAGES --> Macrophage presents foreign antigen in combination with "self-antigen"
                    • secrete cytokines that "help" the immune response:
                      • B cell growth factor - enhances antibody-secreting ability of B cells
                      • Interleukin 2 - enhances activity of cytotoxic T cells, suppressor T cells, & even other helper T cells
                      • Chemotaxins - attract neutrophils & macrophages
                      • Macrophage-migration inhibiting factor - inhibits migration plus creates "angry macrophages"
                      • limit responses of other cells (B & T cells see figure below)
                      • make immune response self-limiting
                      • prevents excessive immune response which might be detrimental to body
                      • may also prevent immune system from attacking a person's own cells & tissues (= TOLERANCE)

                      Regulatory T (TReg) cells are essential for maintaining tolerance, preventing
                      autoimmune diseases, and limiting chronic inflammatory diseases (Vignali et al. 2008).

                        1 - reduction in suppressor T cell activity

                      2 - normal self-antigens modified by drugs, environmental chemicals, viruses, or mutations

                      3 - exposure to antigen very similar to self-antigen ("molecular mimicry")


                      Major autoimmune diseases (Source: www.cdc.gov)


                      Source: ghr.nlm.nih.gov

                      • produced if antigen is not present
                      • produced because common intestinal bacteria have A- & B-like antigens
                      • produced by age of about 6 months

                      If you mix anti-A antibodies with blood cells that have the A antigen OR mix anti-B antibodies with blood cells that have the B antigen, the results will be AGGLUTINATION (or clumping of red blood cells). This reaction can be used to type blood. You simply take two drops of 'unknown' blood and place a drop of anti-A antibody solution on one blood drop & a drop of anti-B antibody solution on the other blood drop. Then, look closely to see if any clumping occurs. If clumping occurs in the drop of blood where you added the anti-A antibodies, then you know that the A antigen is present (and, of course, if there is no clumping, then the A antigen is not present). If clumping occurs in the drop of blood where you added the anti-B antibodies, then you know that the B antigen is present (and, of course, if there is no clumping, then the B antigen is not present). Using this information, you can determine the blood type:

                      Drop of blood in which
                      anti-A antibody was added
                      Drop of blood in which
                      anti-B antibody was added
                      Blood type
                      Clumping No clumping A
                      No clumping Clumping B
                      Clumping Clumping AB
                      No clumping No clumping O

                      Type O blood is the most common blood type, followed by type A, type B, and, the least common blood type, AB.


                      O+ 37%, O- 6%, A+ 34%, A- 6%,
                      B+ 10%, B- 2%, AB+ 4%, AB- 1%

                      In the above chart, the blood types are listed with either a + or -. The + or - refers to the presence or absence of the Rh factor.

                      • universele skenker
                      • no antigens = no clumping
                      • universal recipient
                      • no antibodies = no clumping
                      • inherited independent of ABO system
                      • Rh positive = antigen present on RBCs (& no antibodies)
                      • Rh negative = no antigen & antibodies will be produced IF exposure occurs
                      • hemolysis of RBCs of fetus which can cause anemia or worse
                      • may occur when an Rh negative mother & Rh positive father have an Rh positive fetus
                      • treatment for Rh disease contains antibodies specific for Rh positive antigen (a good example of passive immunity)
                      • injected within 72 hours after birth of Rh positive baby

                      Iwasaki, A., and R. Medzhitov. 2010. Regulation of adaptive immunity by the innate immune system. Science 327:291-295.