Innate And Adaptive Immune Memory: Ib qho Evolutionary Continuum hauv Tus Tswv Cuab Teb rau Cov Kab Mob (Part 1)
Jun 08, 2022
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Immunological ncoyog ib qho tseem ceeb evolutionary yam ntxwv uas txhim kho tus tswv ciaj sia nyob rau hauv reinfection, Nco yog ib tug yam ntxwv pom nyob rau hauv lub innate thiab adaptive caj npab ntawm lub cev tiv thaiv kab mob. Txawm hais tias cov txheej txheem thiab cov khoom siv los ntawm kev ua kom lub cev tsis muaj zog thiab hloov kho lub cev tiv thaiv kab mob yog qhov sib txawv, lawv sib koom ua ke los txhim kho tus tswv tsev tiv thaiv kab mob. Ntawm no, peb tawm tswv yim tias lub cev tiv thaiv kab mob hauv lub cev, lossis "kev tiv thaiv kev tiv thaiv," yog ib qho tseem ceeb ntawm kev hloov kho hauv kev tiv thaiv tus tswv, uas tshwm sim los ntawm cov qauv chromatin rov, uas muab kev nce ntxiv tab sis tsis yog cov lus teb rau kev rov ua dua tshiab. Nyob rau hauv sib piv, adaptive immune nco yog ntau tshaj, nrog ib tug ntau zog ntawm cov lus teb kho los ntawm cov kev hloov ntawm epigenetic, raws li zoo raws li tshwj xeeb kho los ntawmgene recombination. Ib qho kev sib koom ua ke ntawm kev tiv thaiv kab mob nco yog qhov tseem ceeb rau kev nkag siab dav ntawm kev tiv thaiv tus tswv, thiab txhawm rau txheeb xyuas cov txheej txheem zoo tshaj plaws los hloov kho nws rau cov txiaj ntsig ntawm cov neeg mob uas muaj kab mob thiab tiv thaiv kab mob.
Nyem qhov no kom paub ntau ntxiv txog Cistanche
Innate thiab Adaptive Immunity
Classically, tus tswv tsev tiv thaiv yog muab faib ua innate thiab adaptive tiv thaiv kab mob. Tus qub reacts sai thiab tsis yog tshwj xeeb rau cov kab mob, whereas lub tom kawg teb nyob rau hauv ib tug qeeb qeeb tab sis tshwj xeeb yam, nrog rau tiam ntawm lub neej nyob rau hauv lub immunological nco (Farber li al., 2016). Qhov no dichotomy tau hais txog ib nrab xyoo dhau loskev tshawb fawb immunological, thiab ntau cov kev tshawb fawb tau txhais cov cellular thiab molecular substrates ntawm txhua ntawm ob qho tseem ceeb ntawm kev tiv thaiv tus tswv. Innate tiv thaiv kab mob yog kho los ntawm innate immune cell pej xeem xws li myeloid cells, natural killer (NK) cells, thiab innate lymphoid cells (tab sis cov hlwb tsis tiv thaiv kab mob hauv cov xwm txheej tshwj xeeb ib yam), nrog rau cov txheej txheem humoral qub xws li defensins thiab ntxiv. . Adaptive immunity yog ib qho tshiab evolutionary zoo raws li cov tsev neeg immunoglobulin thiab hlwb xws li B- thiab T-lymphocytes nyob rau hauv lub puab tsaig vertebrates (Danilova, 2012) thiab nyob rau hauv variable lymphocyte receptors (VLR) muaj xws li leucine-nplua nuj-repeatments (LRR) nyob rau hauv lub puab tsaig tsis muaj lub puab tsaig (Boehm li al., 2012).
Thaum muaj tus kab mob, kev tiv thaiv kab mob hauv lub cev yog thawj zaug tshwm sim (cov tshuaj tiv thaiv kab mob), siv sijhawm ntev dua li feeb mus rau teev kom ua tiav (Netea li al.,2017). Qhov no yog qhov tseem ceeb rau tus tswv tsev tiv thaiv hauv thawj theem ntawm tus kab mob tshiab. Thaum lub cev tiv thaiv kab mob feem ntau muaj peev xwm tshem tawm cov kab mob tau zoo, kev tshem tawm thawj zaug ntawm tus kab mob tuaj yeem ua tsis tiav vim muaj tus lej ntau lossis kev ua phem ntawminvading cov kab mob. Hauv cov xwm txheej no, lymphocytes thiab hloov kho lub cev tiv thaiv kab mob tau qhib, uas tso cai rau kev paub tshwj xeeb thiab tshem tawm cov kab mob. Kev tsim kho lub cev tiv thaiv kab mob xav tau 1-2 lub lis piam thiab tseem ceeb rau kev tiv thaiv tus tswv thaum lub sij hawm tom kawg ntawm kev kis kab mob thiab thaum kis kab mob thib ob vim nws lub peev xwm "nco" thiab teb tau zoo dua rau kev rov ua dua (Farber et al.,2016) .
Cov txheej txheem tiv thaiv kab mob hauv lub cev thiab hloov pauv tau pib pom tias muaj cov lus teb sib xyaw ua ke nyob rau lub sijhawm, tab sis kev tshawb fawb hauv ob lub xyoo dhau los tau pom meej tias muaj kev sib txuas zoo thiab kev sib txuas zoo ntawm lawv. Kev ua kom lub cev tiv thaiv kab mob hloov pauv thiab induction ntawm classical tiv thaiv kab mob hauv cov lymphocytes yog nyob ntawm lub cev tiv thaiv kab mob, tshwj xeeb tshaj yog nyob rau hauv cov tshuaj tiv thaiv kab mob xws li dendritic hlwb. Cov teebmeem hauv qab ntawm kev ua kom cov lymphocyte yog tom qab ntawd los ntawm kev ua kom lub cev tiv thaiv kab mob hauv lub cev xws li phagocytosis thiab tua cov kab mob los ntawm qee lub cev tiv thaiv kab mob. Ob yam khoom uas muaj kev ntxub ntxaug ntawm innate thiab adaptive tiv thaiv yog nyob rau ntawm ib sab tes tshwj xeeb, thiab ntawm qhov tod tes, lub peev xwm los tsim kom muaj lub neej ntev kev tiv thaiv kab mob. Cov lus teb hauv lub cev tsis muaj zog yog ib txwm xav tias tsis yog tshwj xeeb thiab tsis muaj peev xwm hloov tau, qhov kev hloov kho lub cev tiv thaiv kab mob pom tau tias muaj cov kab mob sib txawv zoo uas siv cov txheej txheem gene recombination hauv tsev neeg immunoglobulin, thiab tom qab tsim kev tiv thaiv kab mob (Danilova, 2012) (Daim duab 1). Lub tswv yim hais tias kev tiv thaiv innate tsis yog tshwj xeeb tau raug sib tw los ntawm kev tshawb pom ntawm tus qauv lees paub receptors (PRR). Cov receptors no tau hais tawm ntawm ntau lub hlwb hauv lub cev tiv thaiv kab mob hauv lub cev paub txog qee yam ntawmkab mob, thiab kev sib xyaw ua ke ntawm PRRs qhia los ntawm lub cev tiv thaiv kab mob tuaj yeem ua rau qee qhov kev paub tshwj xeeb ntawm hom kab mob uas tau ntsib: piv txwv li, lub cev tiv thaiv kab mob hauv lub cev paub qhov txawv ntawm Gram-negative thiab Gram-positive kab mob, tab sis tsis yog ntawm ob qho tib si. Lwm hom lossis hom kab mob (Medzhitov thiab Janeway, 2000). Peb yuav tsis tham txog qhov kev nce qib hauv kev nkag siab txog kev paub txog kab mob los ntawm PRRs hauv qhov kev tshuaj xyuas no, vim qhov no yog cov ntsiab lus ntawm ntau cov lus pom zoo tsis ntev los no hauv cov ntaub ntawv (xws li O'Neill li al., 2013).
Daim duab 1. Innate versus Adaptive Immune Responses
Thaum thawj teev thiab hnub ntawm kev kis tus kab mob, kev ntxeem tau los ntawm cov kab mob ua rau muaj kev ua kom lub cev tsis muaj zog xws li macrophages, monocytes, lossis NK hlwb lossis cov yam ntxwv lom zem xws li ntxiv. Cov txheej txheem no ua kom muaj cov tshuaj tiv thaiv inflammatory thiab tshem tawm cov kab mob (innate tiv thaiv). Hauv qee kis thaum tus kab mob tsis raug tshem tawm, cov kab mob tau noj thiab ua tiav los ntawm cov tshuaj tiv thaiv kab mob tam sim no, tom qab ntawd los ntawm kev nthuav qhia antigen thiab txhawb kev ua kom muaj zog tshwj xeeb.T- thiab B-lymphocytes. Nyob rau hauv lem, qhov no ua rau clonal expansion thiab ua kom cov nyhuv ntawm cov mechanisms (xws li, tso tawm cytokines, thiab immunoglobulins) (adaptive immunity).
Ntawm no, peb yuav tsom mus rau qhov thib ob cov cuab yeej kev ntxub ntxaug innate thiab adaptive host defense mechanisms: induction ntawm lub cev tsis muaj zog. Nyob rau hauv sib piv rau cov ntaub ntawv thaum ntxov, ib lub cev loj hlob ntawm cov pov thawj qhia tau hais tias innate lub cev tiv thaiv kab mob muaj cov yam ntxwv adaptive (Bowdish li al., 2007; Netea li al., 2011). Nyob rau hauv cov nroj tsuag thiab invertebrates uas tsis muaj kev tiv thaiv kab mob, kev tiv thaiv kev tiv thaiv kev tiv thaiv kab mob tau raug tshaj tawm (Kurtz, 2005). Cov kev tshawb fawb hauv cov tsiaj txhu tau pom tias muaj kev tiv thaiv kab mob sib txawv nrog cov kab mob sib txawv (Quintin li al, 2014), thaum cov kev tshawb fawb ntawm cov nas uas tsis muaj lub cev tiv thaiv kab mob tau pom muaj kev tiv thaiv ib feem hauv qee cov qauv ntawm kev txhaj tshuaj (Bistoni li al., 1986; Can't Wout et al, 1992). Nws yog li pom tseeb tias kev tiv thaiv hauv lub cev tuaj yeem hloov kho los ntawm kev sib ntsib yav dhau los nrog cov kab mob microbes lossis cov khoom siv microbial, thiab cov cuab yeej no tau raug hu ua "kev tiv thaiv kab mob" thiab sawv cev rau lub cim xeeb ntawm lub cev tsis muaj zog.
Txawm li cas los xij, muaj cov txheej txheem molecular sib txawv uas kho ob hom kev tiv thaiv kab mob. Raws li kev sib cav molecular, immunological, thiab evolutionary sib cav, peb hais tias innate immune nco yog ib qho tseem ceeb ntawm lub cev tiv thaiv kab mob nyob rau hauv tag nrho cov kab mob nyob, thaum adaptive immune nco yog ib tug siab heev daim ntawv ntawm lub cev tiv thaiv kab mob sawv cev rau ib tug evolutionary innovation nyob rau hauv vertebrates. Raws li cov khoom sib xyaw ua ke ntawm ob hom kev tiv thaiv kab mob, thiab ntawm ntau qhov kev sib cav lom neeg raws li tau piav qhia hauv qab no, peb sib cav hauv qhov Kev Pom Zoo no tias kev loj hlob ntawm innate thiab adaptive immune nco sawv cev rau evolutionary continuum. Peb kuj xav hais tias ob daim ntawv no yog ob kauj ruam evolutionary mus rau txoj kev loj hlob ntawm zoo mechanisms ntawm adaptation rau ib puag ncig teeming nrog tej yam pathogenic.kab mob.
Immunological Memory raws li ib tug Adaptive Evolutionary Trait
Lub dogma uas immunological nco yog nyob rau hauv lub adaptive lub cev tiv thaiv kab mob ntsib ib tug tswv yim nyuaj thaum txiav txim los ntawm ib tug evolutionary foundations. Lub cev tiv thaiv kab mob no muaj txiaj ntsig zoo los ntawm qhov kev hloov pauv ntawm qhov kev xav tau pom zoo los ntawm cov kab mob thaum ub uas tuag taus xws li kab mob me me: thaum kev tuag yog keeb kwm 20 feem pua -60 feem pua rau thawj kis, cov tib neeg tau tiv thaiv kab mob tag nrho tom qab ntawd (Riedel, 2005 ). Yog li ntawd, nws yog ib qho nyuaj rau xav txog tias lub cev tsis nco qab hloov zuj zus nyob rau hauv cov vertebrates, uas sawv cev kwv yees li 1 feem pua -2 feem pua ntawm cov tsiaj nyob (Gourbal li al.,2018). Piv txwv li, lwm yam tseem ceeb muaj txiaj ntsig zoo, xws li lub zeem muag, evolved ntawm nws tus kheej ob peb zaug thaum lub sij hawm evolution ntawm ntau pawg tsiaj (hu ua "convergent evolution") (Gehring, 2004). Txaus siab heev,immunological nconyob rau hauv lub vertebrate kab mob evolved tsis yog ib zaug, tab sis ob zaug. Ua ntej, txoj kev loj hlob ntawm VLR-raws li lub cim xeeb nyob rau hauv lub puab tsaig ntses (xws li lub lamprey) thiab, qhov thib ob, txoj kev loj hlob ntawm LG-based nco (uas kuj yog lub hauv paus rau kev loj hlob ntawm B- thiab T-lymphocyte nco) nyob rau hauv tag nrho lwm cov jawed vertebrates. Tias yuav muaj ob qhov xwm txheej sib cais ua rau lub cev tsis muaj zog hauv cov pob txha (Cooper thiab Alder, 2006), thaum tsis tuaj yeem ua tiav hauv tag nrho lwm cov metazoans, yog qhov tsis zoo li.
Daim duab 2. Immune Memory versus Immune Adaptation
Lub cev tiv thaiv kab mob yog txhais tau tias yog qhov hloov pauv ntawm lub cev tiv thaiv kab mob ntawm tus tswv tsev tom qab kis mob hnyav (lossis txhaj tshuaj tiv thaiv), ua rau muaj txiaj ntsig zoo dua rau kev rov ua dua tshiab. Qhov tseem ceeb, thaum lub sij hawm induction ntawm lub cev tiv thaiv kab mob, nruab nrab ntawm thawj tus kab mob thiab rov kis kab mob, lub cev tiv thaiv kab mob ua hauj lwm rov qab mus rau ib tug tsawg basal xeev, thaum lub peev xwm los teb muaj zog rau restimulation yog imprinted nyob rau hauv lub epigenetic theem (A). Hauv qhov sib piv, kev hloov pauv tau txhais tau tias yog qhov hloov pauv mus ntev hauv lub cev tiv thaiv kab mob txiav txim siab los ntawm kev hloov pauv tsis tu ncua ntawm ib puag ncig, lossis vim muaj kev thuam tsis zoo (piv txwv li, kab mob ntev), ua rau lub xeev ua haujlwm tshiab. Qhov tseem ceeb, kev ua haujlwm ntawm lub cev tiv thaiv kab mob thaum hloov pauv tsis rov qab mus rau lub xeev qis qis uas twb muaj lawm ua ntej kev thuam (B).
Nyob rau hauv txoj kab nrog qhov no, ntau cov kev tshawb fawb ntawm cov nroj tsuag tiv thaiv kab mob tau pom tias cov nroj tsuag tiv thaiv muaj xws li cov yam ntxwv hloov, cov lus teb hu ua Systemic Acquired Resistance (SAR)(Jaskiewicz li al.,2011; Kachroo and Robin, 2013; Reimer-Michalski thiab. Conrath, 2016). Cov txheej txheem molecular thiab biochemical mediators ntawm SAR feem ntau paub (Kachroo thiab Robin, 2013), nrog epigenetic-raws li rewiring ntawm tus tswv tsev tiv thaiv raug pom zoo los ua lub luag haujlwm tseem ceeb (Luna thiab Ton, 2012). kev ntseeg tias invertebrate innate tiv thaiv tsis muaj kev nco zoo (Kurtz, 2005). Adaptive zog ntawm innate tiv thaiv teb tau raug tshaj tawm nyob rau hauv ob peb invertebrate kab mob; eg, covmicrobiotatau pom tias ua rau muaj kev tiv thaiv kab mob hauv lub cev los tiv thaiv yoov tshaj cum tiv thaiv Plasmodium (Rodrigues li al, 2010), thiab cov kab sib raug zoo Bombus Terrestris los tso saib lub cev tiv thaiv kab mob tiv thaiv peb cov kab mob sib txawv (Sadd thiab Schmid-Hempel, 2006), thiab tapeworm Schistocephalus. solidus rau induce nco nyob rau hauv copepod crustacean (Kurtz thiab Franz, 2003), thiab innate immune nco yog ib tug tiv thaiv mechanism nyob rau hauv qwj (Pinaud li al, 2016). Cov kev tshawb fawb no tau ua tiav los ntawm cov ntaub ntawv hauv vertebrates uas qhia tau hais tias nws muaj peev xwm ua rau muaj kev tiv thaiv ib nrab los ntawm kev rov ua dua tshiab hauv kev sim murine qauv txawm tias tsis muaj kev hloov pauv lub cev tiv thaiv kab mob (Bistoni li al.,1986; tsis tuaj yeem Wout li al.,1992. ). Ntxiv mus, kev tshawb fawb txog kab mob kis tau pom muaj kev tiv thaiv heterologous los ntawm tib neeg cov tshuaj tiv thaiv tiv thaiv kab mob dav dav (Benn li al., 2013), nrog cov txheej txheem yuav muaj kev ywj pheej los ntawm cov lus teb rau kev tiv thaiv kab mob. Yog li ntawd, nws yog ib qho tsim nyog los txiav txim siab tias kev nco txog kev tiv thaiv kab mob tuaj yeem pom tsis tau tsuas yog hauv cov kab mob vertebrates tab sis kuj nyob rau hauv cov nroj tsuag thiab cov tsiaj qis (Kurtz, 2005; Ne-tea et al., 2011) uas tsis muaj lub cev tiv thaiv kab mob classical adaptive.
Innate thiab Adaptive Immune Memory: Ib Txoj Kev Evolutionary
Yog tias cov ntaub ntawv no tau sib cav txog qhov muaj lub cev tiv thaiv kab mob hauv txhua pawg ntawm cov kab mob siab dua, qhov no txhais tau li cas? Ib qho yooj yim txhais yog tias kev nco txog kev tiv thaiv kab mob yog hais txog lub peev xwm ntawm lub cev tiv thaiv kab mob los teb sai dua thiab zoo rau cov kab mob. Qhov kev txhais no suav nrog tag nrho cov txheej txheem piav qhia ua lub cim xeeb tiv thaiv kab mob hauv cov nroj tsuag, invertebrates, thiab vertebrates, txawm hais tias nws tsis muaj kev ntxub ntxaug ntawm qhov sib txawv ntawm qhov kev txiav txim pom nyob rau hauv ntau pawg kab mob. Hauv kev tshuaj xyuas tsis ntev los no, Pradeu thiab Du Pasquier (2018) qhia txog ntau qhov qauv ntawm lub cev tiv thaiv kab mob, uas lawv cais tsis tsawg tshaj li rau ntau hom kev tiv thaiv kab mob: classical adaptive nco hauv vertebrates, NK-cell tiv thaiv kab mob nco, kawm tiv thaiv kab mob hauv myeloid hlwb. , priming invertebrates, immunological nco nyob rau hauv cov nroj tsuag (xws li, SAR), thiab Crispr/Cas-raws li nco nyob rau hauv cov kab mob thiab archaea (Pradeu thiab Du Pasquier, 2018). Cov ntaub ntawv ntawm kev tiv thaiv kab mob tiv thaiv kab mob no txawv ntawm lawv cov khoom raws li tus lej ntawm cov yam ntxwv tseem ceeb ntawm cov lus teb: lub zog, nrawm, ploj mus (rov qab mus rau lub xeev basal), lub sijhawm, thiab qhov tshwj xeeb. Txawm li cas los xij, thaum qhov kev faib tawm no muaj txiaj ntsig zoo rau kev nkag siab txog qhov muaj nyob hauv lub cev tiv thaiv kab mob hauv txhua yam kab mob, peb ntseeg tias qhov no.compartmentalizationntawm lub cev tiv thaiv kab mob tsis muaj kev cuam tshuam txog cov molecular, lom, thiab kev ua haujlwm ntawm lub cim xeeb ntawm cov kab mob sib txawv.
Hauv qhov Kev Pom Zoo no, peb nthuav tawm cov qauv kev sib koom ua ke ntawm kev tiv thaiv kab mob uas ua raws li ob lub ntsiab lus:
Muaj lub tswv yim sib txawv ntawm ob hom kev tiv thaiv kab mob: kev tiv thaiv kab mob thiab kev tiv thaiv kab mob sib txawv.
Ib qho evolutionary continuum txuas innate thiab adaptive immune nco.
Thawj lub tswv yim uas yuav tsum tau txhais yog sawv cev los ntawm qhov sib txawv ntawm kev tiv thaiv kab mob thiab kev tiv thaiv kab mob. Peb txhais lub cim xeeb tiv thaiv kab mob raws li qhov hloov pauv ntawm lub cev tiv thaiv kab mob ntawm tus tswv tsev tom qab kis mob hnyav (lossis txhaj tshuaj tiv thaiv), ua rau muaj txiaj ntsig zoo dua los tiv thaiv kev kis kab mob. Qhov tseem ceeb, thaum lub sij hawm induction ntawm lub cev tiv thaiv kab mob, nruab nrab ntawm thawj tus kab mob thiab reinfection, lub cev tiv thaiv kab mob ua hauj lwm rov qab mus rau ib tug tsawg basal xeev, thaum lub peev xwm los teb muaj zog rau restimulation yog imprinted nyob rau hauv lub epigenetic theem (Daim duab 2A). Hauv qhov sib piv, peb txhais cov kev tiv thaiv kab mob sib txawv raws li ib qho kev hloov pauv los ntawm kev hloov mus sij hawm ntev hauv kev ua haujlwm ntawm lub cev (xws li lub cev tiv thaiv kab mob), txiav txim siab los ntawm kev hloov pauv tsis tu ncua ntawm ib puag ncig lossis vim muaj kev saib tsis taus ntev (xws li, mob ntev. kab mob), ua rau lub xeev ua haujlwm tshiab. Qhov tseem ceeb, kev ua haujlwm ntawm lub cev tsis muaj zog thaum lub sijhawm sib txawv tsis rov qab mus rau lub xeev qis qis uas twb muaj lawm ua ntej kev thuam (Daim duab 2B). Muaj ntau qhov xwm txheej lom neeg uas muaj kev hloov pauv los ntawm kev tiv thaiv kab mob sib txawv: ib qho xwm txheej zoo li no yuav raug ntxias piv txwv los ntawm kev hloov pauv hauv plab microbiota, uas paub tias yuav ua rau muaj kev cuam tshuam ntev rau lub cev tiv thaiv kab mob hauv zos. Cov txheej txheem ntawm kev tiv thaiv kab mob sib txawv yog cov ntsiab lus ntawm ntau lwm yam kev tshuaj xyuas zoo, thiab nws yuav tsis yog qhov tseem ceeb ntawm Kev Pom Zoo no.
Lwm qhov kev sib txawv tseem ceeb los ua yog nruab nrab ntawm kev sib tw thiab kev nco. Priming kuj yog ib lo lus uas tau siv los piav qhia txog cov lus teb nce ntxiv rau qhov kev txhawb siab thib ob, txawm li cas los xij, qhov no feem ntau yog cov txheej txheem mob uas tsis cuam tshuam txog kev nco mus ntev. Piv txwv li, thaum muaj tus kab mob malaria mob hnyav, muaj qhov paub zoo txog kev ua haujlwm ntawm lub cev tiv thaiv kab mob rau cov kab mob Gram-tsis zoo uas tuaj yeem ua rau cov tsos mob hnyav heev: lub cev tiv thaiv kab mob yog primed los teb acutely nrog ntau dua cytokine tso. Txawm li cas los xij, qhov ntawd tsis txhais hais tias lub cim xeeb teb uas yuav nyob mus ib hlis lossis xyoo.
Ntawm no, peb yuav tsom mus rau lub tswv yim ntawm kev tiv thaiv kab mob, uas peb ntseeg hais tias tus yam ntxwv ntawm tag nrho cov kab mob nyob. Peb npaj siab tias muaj kev hloov pauv txuas ntxiv ntawm lub cev thiab lub cev tiv thaiv kab mob hloov pauv raws li ob qho tseem ceeb sib kho los ntawm cov txheej txheem sib txawv:
● Nce qhov loj thiab kinetics ntawm lub cev tiv thaiv kab mob
cov lus teb thaum rov ua dua tshiab, uas yog kho los ntawm cov txheej txheem epigenetic thiab ua rau ob qho tib si hauv lub cev thiab lub cev tiv thaiv kab mob (tam sim no hauv txhua yam kab mob)
● Qhov tshwj xeeb ntawm cov lus teb nco, kho los ntawm noob
recombination, ib qho cuab yeej tshwj xeeb rau kev ua kom lub cev tiv thaiv kab mob (tshwj xeeb txog tam sim no tsuas yog hauv cov vertebrates)
Innate Immune Nco
Thaum nyob rau hauv vertebrate tiv thaiv kab mob nws tau ntev tau xav tias innate lub cev tiv thaiv kab mob tsis tuaj yeem hloov tau tom qab kis kab mob, thiab thaum rov ua dua tshiab, cov lus teb zoo ib yam yog elicited txhua zaus, qhov kev xav no tsis tau ua raws li hauv cov nroj tsuag lossis invertebrate tiv thaiv. Ntxiv rau cov kev tshawb fawb ntawm cov nroj tsuag thiab invertebrate tus tswv tsev tiv thaiv tau piav qhia saum toj no (saib Immunological Memory raws li Adaptive Evolutionary Trait), ntau lub tswv yim tau thov kom suav nrog kev ua kom lub cev tiv thaiv kab mob hauv lub cev tsis muaj zog, suav nrog kev txhawb nqa lossis "kev cob qhia" ntawm txoj kev tswj hwm xws li Raws li Tus Xov Tooj lossis Imd (Boutros li al, 2002) thiab ntau thiab phenotypic hloov pauv hauv cov neeg tiv thaiv kab mob (Ro-drigues li al., 2010). Qee cov kws tshawb nrhiav kuj tau hais txog qhov muaj ntau haiv neeg-tsim mechanisms hauv kab. Cov txheej txheem zoo li no tuaj yeem koom nrog cov proteins uas cuam tshuam nrog fibrinogen nrog cov nqi sib txawv ntawm qib genomic (Zhang li al., 2004) lossis kev txhawb nqa ntawm kev qhia tshwj xeeb receptors xws li peptidoglycan lees paub cov molecules thiab lectins (Steiner, 2004).
Cov ntsiab lus tseem ceeb uas vertebrate innate tiv thaiv kab mob kuj muaj cov yam ntxwv hloov tau raug tshaj tawm hauv kev sim kev tshawb fawb hauv nas. Ob peb cov kev tshawb fawb no tau pom tias priming lossis cob qhia nas nrog microbial ligands tuaj yeem tiv thaiv kab mob tuag taus. Piv txwv li, kev kawm tiv thaiv kab mob los ntawm -glucan (los ntawm cov kab mob fungi) ua rau muaj kev tiv thaiv kab mob nrog Staphylococcus aureus (Di Luzio thiab Williams, 1978; Marakalala li al, 2013). Ib yam li ntawd, cov kab mob peptidoglycan tivthaiv muramyl dipeptide induces tiv thaiv Toxoplasma (Krahenbuhl li al,1981), thiab CpG oligodeoxynucleotide tswj xyuas tiv thaiv sepsis thiab Escherichia coli meningitis (Ribes li al, 2014). Tsis tas li ntawd, flagellin los ntawm cov kab mob Gram-tsis zoo tuaj yeem ua rau muaj kev tiv thaiv kab mob Gram-positive Streptococcus pneumoniae (Munoz li al., 2010) thiab rotavirus (Zhang li al., 2014a). Ntxiv nrog rau cov kab mob microbial ligands, muaj pov thawj tias qee cov cytokines pro-inflammatory tuaj yeem ua rau muaj kev tiv thaiv kab mob: kab mob ntawm cov nas nrog ib koob ntawm recombinant IL-1 peb hnub ua ntej kis kab mob Pseudo-monas aeruginosa tiv thaiv nas tiv thaiv kev tuag (van der Meer et al., 1988). Tus cwj pwm tsis tshwj xeeb ntawm kev kawm tiv thaiv kab mob sib cav tawm tsam qhov kev nco qub qub uas tau kho los ntawm kev tiv thaiv kab mob thiab qhia txog kev ua kom lub cev tsis muaj zog hauv lub cev. Ib qho tseem ceeb uas yuav tsum tau tshawb xyuas yog lub sij hawm ntawm kev tiv thaiv kev tiv thaiv kev tiv thaiv. Cov kev tshawb fawb hauv nas thiab tib neeg tau pom cov teebmeem tom qab 3 lub hlis thiab txawm tias ib xyoos (Kleinnijenhuis li al, 2014), txawm hais tias cov ntaub ntawv kis kabmob raws li kev tiv thaiv heterologous los ntawm cov tshuaj tiv thaiv qhia tias lawv yuav ua haujlwm tsawg kawg yog 3-rau 5. xyoo.
Kev tiv thaiv kab mob tuaj yeem kho yam tsawg kawg yog qee qhov kev tiv thaiv ntawm kev txhaj tshuaj. Cov pov thawj tsis txaus ntseeg los ntawm cov kev tshawb fawb qhia tias kev txhaj tshuaj tiv thaiv kab mob ntsws bacillus Calmette Guerin (BCG), cov tshuaj tiv thaiv feem ntau siv thoob ntiaj teb, ua rau T cell- ywj pheej tiv thaiv kab mob thib ob nrog Candida albicans, Schistosoma mansoni, lossis kab mob khaub thuas hauv tsiaj (Spencer et al. .,1977; Tribouley et al.1978; tsis tau Wout et al.,1992). Tib neeg cov ntaub ntawv ua tiav cov kev tshawb fawb no: Kev txhaj tshuaj BCG hauv tib neeg tuaj yeem pab tiv thaiv kev sim kab mob nrog cov tshuaj tiv thaiv kab mob ua npaws daj (Arts li al, 2018), thaum cov kev tshawb fawb loj loj tau tshaj tawm txog kev tiv thaiv heterologous rau BCG thiab tshuaj tiv thaiv kab mob qhua pias (Benn li al, 2013 Goodridge li al, 2016). Tsis tas li ntawd, herpesvirus latency nce resistant mus rau cov kab mob pathogens Listeria monocytogenes thiab Yersinia pestis (Barton li al., 2007) nrog kev tiv thaiv ua tiav los ntawm kev txhim kho kev tsim tawm ntawm IFNy thiab kev ua haujlwm ntawm macrophages. Ib yam li ntawd, kev kis kab mob nrog cov kab mob helminthic Nip-strongyles brasiliensis induces ib lub sij hawm ntev macrophage phenotype uas ua rau cov cab thiab induces tiv thaiv los ntawm reinfection ntawm T thiab B lymphocytes (Chen li al., 2014).
Cov cell loj uas tau tshaj tawm tias yog lub luag haujlwm rau kev tiv thaiv kab mob hauv lub cev yog monocytes, monocyte-derived macrophages, thiab natural killer (NK) hlwb. Whereas macrophage-dependent tiv thaiv theem nrab los ntawm kev kis kab mob tsis yog tshwj xeeb, NK cell-mediated immune memory tuaj yeem muab qhov tshwj xeeb ntxiv. Thawj cov pov thawj ntawm NK cell nco tau los ntawm kev soj ntsuam ntawm cov nas sib txawv T thiab B cell-tsis muaj nas (RAG knockout, SCID, thiab nu/nu) tuaj yeem txhim kho cov lus teb rov qab zoo rau cov tshuaj tiv thaiv kev sib raug zoo (O'Leary et ib., 2006). NK hlwb tuaj yeem kho cov kev sib cuag tshwj xeebhypersensitivity(CHS) nyob rau hauv cov tsiaj no, tsis tau NK cell nco yog txwv rau lub siab-nyob hlwb hlwb ntawm NK.1.1 ntxiv rau DX5-CXCR6 ntxiv rau CD49a ntxiv phenotype (OLeary li al,2006; Paust li al,2010; Peng et al., 2013). Nas lub siab-neeg nyob hauv NK hlwb tuaj yeem tsim cov cim xeeb tshwj xeeb rau ntau hom haptens thiab lwm yam antigens, suav nrog cov kab mob zoo li cov kab mob (VLPs); Txawm li cas los xij, qhov kev paub txog antigen tsis paub (Paust li al., 2010). Antigen tshwj xeeb thiab kav ntev (splenic thiab hepatic) NK nco cell teb kuj tau pom nyob rau hauv rhesus macaques, qhia tias antigen-specific nco NK hlwb kuj muaj nyob rau hauv tib neeg (Reeves li al., 2015)
NK hlwb tuaj yeem qhib tau los ntawm cytomegalovirus: tom qab kis kab mob murine cytomegalovirus (mCMV) (Nabekura li al, 2015; Schlums li al., 2015; Sun et al, 2009; Sunset al., 2012), NK cells bearing Ly49H receptor prophylaxis. , mob nyob rau hauv lymphoid thiab non-lymphoid organ thaum lub sij hawm contraction theem ntawm NK cell teb. Thaum rov ua dua tshiab, cov "nco" NK hlwb tau txais kev nthuav dav ntxiv, sai sai degranulating thiab tso tawm cytokines, yog li ua rau muaj kev tiv thaiv tiv thaiv kab mob (Sun et al, 2009). Ib tug xov tooj ntawm cov txheej txheem tau muab tso rau pem hauv ntej los piav qhia txog lub cim xeeb ntawm NK hlwb, suav nrog IL-12/IFNy axis (Tshav li al, 2012) lossis ua kom cov co-stimulatory molecule DNAM{{10 }} (DNAX accessory molecule-1, CD226) (Nabekura li al.,2014).
CMV-induced NK nco zoo li tshwj xeeb: cov kev tshawb fawb nas pom tias tsis muaj kev txhawb nqa ntawm mCMV-induced NK nco hlwb tiv thaiv lwm yam kab mob xws li mob npaws lossis Listeria (Min-Oo thiab Lanier, 2014). Ib yam li ntawd, tib neeg kev tshawb fawb qhia tias tsis muaj kev teb ntawm NKG2C ntxiv rau CD57 ntxiv rau NK cell pejxeem nthuav dav hauv tib neeg (H) CMV ntxiv rau cov tib neeg (Hendricks li al, 2014). Cytokine-primed NK hlwb tau pom zoo los txhim kho lub cim xeeb zoo li lub zog. Nas thiab tib neeg NK hlwb txhawb nqa nrog kev sib xyaw ua ke ntawm IL12, IL15, thiab IL18 tau pom kev txhim kho IFNy ntau lawm nyob rau hauv cov lus teb rau qhov kev txhawb siab thib ob nrog cytokines lossis qog hlwb lub lis piam tom qab cytokine priming (Cooper li al., 2009; Keppel li al, 2013 Romee et al., 2012).
Innate lymphoid hlwb pab pawg 2 (ILC2) uas sib koom cov qog ntshav qog ntshav nrog NK, B, thiab T hlwb, tsis muaj cov tshuaj tiv thaiv kab mob tab sis tuaj yeem ua haujlwm los ntawm cytokines. Lawv kuj qhia txog lub peev xwm los "nco" lawv cov xwm txheej ua kom muaj zog thiab ua kom cov lus teb zoo dua thaum muaj kev txhawb siab thib ob. Hauv lub ntsws, nqus tau cov tshuaj tsis haum rau ILC2s los tsim IL-5 thiab IL-13 nyob rau hauv ib qho IL-33-raws li (Halim et al.,2014). Tom qab ua xua ua rau ua xua, lub ntsws ILC2s tau nthuav dav ua raws li theem kev cog lus uas lawv tsis tsim cytokines. Cov pej xeem ntawm allergen-experienced ILC2s nyob rau hauv lub ntsws thiab cov qog nqaij hlav. Raws li qhov kev sib tw thib ob nrog cov tshuaj tsis haum, nco-zoo liILC2s nce lub cev tiv thaiv kab mob ntau dua. Kev nkag siab ntawm cov nas nrog IL-33 tau txaus los tsim lub cim xeeb ILC2s teb rau cov tshuaj tiv thaiv kab mob thib ob uas qhia tias tsis yog-antigen tshwj xeeb ntawm ILC2s nco (Martinez-Gonzalez li al.,2016).
Cov kev soj ntsuam no kuj tseem yuav qhia txog qhov tshwj xeeb ntawm qhov chaw ntawm ILCs thiab NK hlwb ntawm txoj kev hloov pauv hloov pauv ntawm lub cev thiab kev tiv thaiv kab mob.
Muab ua ke, cov kev tshawb fawb ntxiv nrog cov murine thiab tib neeg cov kev tshawb fawb pom tau tias cov lus teb hauv lub cev tiv thaiv kab mob muaj peev xwm ua tau "kev cob qhia" thiab yog li siv hom tshiab ntawm kev tiv thaiv kab mob thaum rov ua dua tshiab, uas lub sij hawm tau txais kev tiv thaiv kab mob (Netea li al, 2016; Netea et al., 2011). Ib qho kev txuas ntxiv ntawm lub tswv yim kev tiv thaiv kab mob tsis ntev los no tau tshaj tawm kom muaj cov kab mob tsis muaj zog tiv thaiv kab mob, xws li cov kab mob epithelial (Cassone, 2018).
