Lub luag haujlwm ntawm kev tiv thaiv kab mob hauv Pathogenesis ntawm SARS-CoV-2 Kev Tiv Thaiv Thiab Hauv Kev Tiv Thaiv Tsim los ntawm COVID-19 Cov tshuaj tiv thaiv nyob rau ntau pawg hnub nyoog Part 1
May 10, 2023
Abstract:
Txoj kev tshawb no yog tsom los tshuaj xyuas cov ntaub ntawv muaj txog lub luag haujlwm tseem ceeb ntawm kev tiv thaiv kab mob hauv kev tiv thaiv kab mob SARS-CoV-2 thiab hauv tiam neeg ntawm kev tiv thaiv los ntawm kev txhaj tshuaj tiv thaiv COVID-19 hauv ntau pawg hnub nyoog. Physiologically, lub cev tiv thaiv kab mob thiab cov khoom uas muaj nyob rau hauv nws yog sib txawv, ob qho tib si functionally thiab ntau npaum, nyob rau hauv cov me nyuam mos, me nyuam mos, me nyuam, cov hluas, thiab cov laus.
Qhov sib txawv ntawm kev tiv thaiv kab mob no tau tsom mus rau lub sijhawm tiv thaiv COVID-19 thiab nyob rau lub sijhawm tom qab txhaj tshuaj tiv thaiv. Qhov tshwm sim ntawm tus kab mob SARS-CoV-2 yog nyob ntawm cov tshuaj tiv thaiv los ntawm lub cev tiv thaiv kab mob. Qhov no pom tseeb hauv qhov chaw kho mob ntawm tus kab mob COVID-19, uas tuaj yeem ua rau tsis muaj tsos mob, mob me, mob me, lossis hnyav. Txawm tias cov teeb meem ntawm tus kab mob no qhia ib tug proportional qauv ntawm lub cev tiv thaiv kab mob. Ntawm qhov tsis sib xws, feem ntau siv tshuaj tiv thaiv COVID-19 cov tshuaj tiv thaiv ua rau muaj kev tiv thaiv kab mob humoral thiab cellular. Qhov loj ntawm qhov kev tiv thaiv kab mob no thiab cov khoom muaj feem cuam tshuam nrog nws tau tham hauv kev nthuav dav. Tsis tas li ntawd, ntau yam tsis zoo ntawm cov tshuaj tiv thaiv no tuaj yeem piav qhia raws li kev tiv thaiv kab mob tiv thaiv kab mob sib txawv ntawm cov tshuaj tiv thaiv. Hais txog kev xaiv cov tshuaj tiv thaiv rau cov hnub nyoog sib txawv, ntau yam yuav tsum tau xav txog.
Kev tiv thaiv humoral tiv thaiv yog ze ze rau kev tiv thaiv. Kev tiv thaiv humoral tiv thaiv yog hais txog qee cov tshuaj tiv thaiv thiab cov hlwb uas muaj nyob hauv cov ntshav, lymph, thiab lwm yam dej hauv tib neeg lub cev, uas tuaj yeem cuam tshuam cov kab mob ncaj qha thiab muab lub cev nrog kev tiv thaiv tseem ceeb. Kev tiv thaiv kab mob yog hais txog kev tiv thaiv ntawm tib neeg lub cev tiv thaiv kab mob rau sab nraud lom neeg ntxeem tau. Yog tias tib neeg kev tiv thaiv qis, nws yuav cuam tshuam rau kev tiv thaiv kev tiv thaiv kev tiv thaiv thiab ua rau muaj kev pheej hmoo ntawm kev kis kab mob. Tib neeg lub cev muaj lub cev tiv thaiv kab mob rau cov kab mob xws li kab mob thiab kab mob, uas yog, kev tiv thaiv hauv lub cev, uas suav nrog kev tiv thaiv hauv zos ntawm daim tawv nqaij, mucous daim nyias nyias, ua pa, siab, ob lub raum, thiab lwm yam kabmob thiab macrophages, neutrophils, ntuj. killer cell, thiab lwm yam cellular tiv thaiv kab mob. Cellular tiv thaiv kab mob thiab kev tiv thaiv humoral yog ob lub hauv paus ntawm lub cev tiv thaiv kab mob, uas tiv thaiv kev cuam tshuam ntawm cov kab mob los ntawm cov tshuaj tiv thaiv kab mob thiab cov tshuaj tiv thaiv kab mob ntawm tes.
Yog li ntawd, qhov muaj zog tiv thaiv kab mob, lub cev muaj peev xwm tiv thaiv kab mob, thiab kev tiv thaiv kev tiv thaiv zoo yuav ua tau zoo dua. Tsim kom muaj kev noj qab nyob zoo thiab noj zaub mov zoo, tswj kev pw tsaug zog txaus thiab kev tawm dag zog kom zoo, txhim kho kev tiv thaiv, thiab pab tiv thaiv kab mob sib kis. Yog li ntawd, peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv. Cistanche muaj ntau yam khoom xyaw lom neeg, xws li polysaccharides, nceb, Huangli, thiab lwm yam, cov khoom xyaw no tuaj yeem txhawb nqa ntau lub hlwb ntawm lub cev thiab ua kom lawv lub cev tiv thaiv kab mob.
Nyem cistanche tag nrho cov zaub mov
Qhov no yog lub hauv paus tseem ceeb, tshwj xeeb tshaj yog nyob rau hauv cov hnub nyoog hauv qab no: 1 hnub rau 5 xyoos, 6 txog 11 xyoo, thiab 12 txog 17 xyoo. Ntau yam muaj feem cuam tshuam rau kev txiav txim siab txoj hauv kev, koob tshuaj, thiab lub sijhawm txhaj tshuaj tiv thaiv rau menyuam yaus. Lwm qhov teeb meem tseem ceeb hauv qhov teeb meem no yog qhov tsis txaus siab ntawm cov tsev neeg hauv kev txiav txim siab seb puas yuav txhaj tshuaj tiv thaiv lawv cov menyuam. Ntxiv rau cov teeb meem no yog kev xaiv los ntawm cov neeg saib xyuas kev noj qab haus huv thiab tsoomfwv txog seb puas yuav tsum txhaj tshuaj tiv thaiv menyuam yaus. Hauv qhov kev hwm no, txawm tias tsis tshua muaj thiab tsawg, qhov tshwm sim tsis zoo ntawm cov tshuaj tiv thaiv hauv cov menyuam yaus tau raug kuaj pom, qee qhov, hmoov tsis, tau mob hnyav lossis tuag taus.
Txawm li cas los xij, kom ua tiav kev tswj hwm kev tiv thaiv COVID-19 hauv cov zej zog, ob qho tib si menyuam yaus thiab cov neeg laus yuav tsum tau txhaj tshuaj tiv thaiv, vim tias yav dhau los pab pawg sawv cev rau lub pas dej rau kev kis tus kabmob. Kev nkag siab ntawm ntau yam kev tiv thaiv kab mob koom nrog hauv SARS-CoV-2 kev kis kab mob thiab kev npaj thiab siv nws cov tshuaj tiv thaiv tau muab txoj hauv kev zoo rau kev tshawb fawb ntxiv thiab nthuav dav kev paub txog kev tiv thaiv kab mob. Qhov no yuav cia siab tias yuav muaj kev cuam tshuam zoo rau lwm yam kab mob los ntawm kev tau txais keeb kwm kev tiv thaiv kab mob uas tuaj yeem pab kho mob thiab kho. Tib neeg tseem nyob hauv kev tsis sib haum xeeb nrog SARS-CoV-2 tus kab mob thiab yuav nyob rau ib ntus, tab sis lub neej yav tom ntej yuav tsum muaj kev pom zoo rau kev tiv thaiv thiab tswj tus kab mob no.
Ntsiab lus:
SARS-CoV-2; COVID-19; cov tshuaj tiv thaiv kab mob; tiv thaiv kab mob; txhaj tshuaj tiv thaiv menyuam; Multisystem inflammatory syndrome nyob rau hauv cov me nyuam (MIS-C).
1. Taw qhia
Hauv Tebchaws Meskas, nrog rau thoob plaws ntiaj teb, tsawg dua cov neeg mob ntawm COVID-19 tau tshaj tawm hauv menyuam yaus dua li cov neeg laus. Lawv sawv cev kwv yees li 17–18 feem pua ntawm tag nrho COVID-19 kis ntawm cov pejxeem [1]. Qhov feem pua ntawm cov menyuam nyob hauv tsev kho mob yog nyob nruab nrab ntawm 1.7 feem pua thiab 4.4 feem pua ntawm tag nrho cov tsev kho mob [2]; Txawm li cas los xij, txog li 50 feem pua ntawm cov menyuam yaus thiab cov tub ntxhais hluas muaj tus kab mob COVID{11}} tsis muaj tsos mob [3]. Qhov no tuaj yeem ua rau pom qhov muaj peev xwm ntawm lub cev tiv thaiv kab mob hauv kev tawm tsam tus kab mob SARS-CoV-2 hauv cov menyuam yaus piv rau cov neeg laus. Vim li no, muaj lus nug: "Vim li cas peb txhaj tshuaj tiv thaiv menyuam yaus?" Lo lus teb rau lo lus nug no yog los tiv thaiv tus kab mob hnyav thiab kis tus kab mob mus rau cov tsev neeg thiab cov zej zog. Tsis tas li ntawd, tsis tshua muaj, cov menyuam yug tshiab tuaj yeem muaj kev pheej hmoo siab kis tus kab mob COVID{15}} ntau dua li cov menyuam loj [3]. Qhov no yog vim lub cev tiv thaiv kab mob hauv cov menyuam mos tseem tsis paub qab hau piv rau cov menyuam loj [3].
Thaum ib tug neeg yug los, ob qho tib si hauv lub cev thiab kev tiv thaiv kab mob kis mus rau tus menyuam yug tshiab los ntawm leej niam ntawm qhov chaw mos thiab thaum pub niam mis, uas tuaj yeem tiv thaiv tus menyuam ib ntus kom txog thaum lawv lub cev tiv thaiv kab mob loj tuaj [4]. Thaum muaj hnub nyoog plaub xyoos, lub cev tiv thaiv kab mob zoo li ua tau zoo dua nrog kev nco zoo ntawm tes. Thaum muaj hnub nyoog 55 xyoos, lub cev tiv thaiv kab mob tau poob qee lub zog thiab kev nco qab los tiv thaiv kab mob. Booster koob tshuaj tiv thaiv tuaj yeem pab txhawb lub cev tiv thaiv kab mob [4].
SARS-CoV-2 tuaj yeem kis tau rau txhua pab pawg hnub nyoog, thiab muaj qhov sib txawv ntawm kev tiv thaiv kab mob thiab qhov tshwm sim ntawm COVID-19 kis ntawm cov pab pawg no. Cov menyuam mos liab, menyuam mos, menyuam yaus, thiab cov tub ntxhais hluas feem ntau kis tus kab mob tsis zoo lossis mob khaub thuas COVID-19 [5–7]. Hauv cov hnub nyoog no, lub cev tiv thaiv kab mob ua haujlwm txawv dua li cov neeg laus. Lub cev tiv thaiv kab mob hauv cov menyuam mos yog tsim los ntawm kev tiv thaiv kab mob tiv thaiv kab mob, tsis yog tiv thaiv kab mob microbes [8,9]. Lub cev tiv thaiv kab mob yog tswj hwm los tiv thaiv kev puas tsuaj ntau dhau rau cov ntaub so ntswg ib txwm [10].
Hauv cov me nyuam mos/cov me nyuam mos, tus naj npawb ntawm cov tshuaj tiv thaiv kab mob tau nce ntxiv kom txo tau cov tshuaj tiv thaiv kab mob uas tsis xav tau, thiab lub luag haujlwm ntawm cov hlwb no tuaj yeem txiav txim siab tus qauv ntawm COVID-19 tshwm sim hauv cov menyuam mos [11]. Thaum kis tus kab mob COVID-19, kev tsim cov cytokines proinflammatory (IL-1ß, IL-6, IL-8, IL-17, thiab TNF- ) kuj yog nruj tswj hwm hauv cov menyuam mos, menyuam mos, thiab menyuam yaus sib piv rau cov neeg laus [12].
Qhov cuam tshuam ntawm tus kab mob SARS-CoV-2 ntawm qhov kev qhia thiab kev ua haujlwm ntawm angiotensin-converting enzyme 2 (ACE2) hauv cov menyuam yaus txawv ntawm cov neeg laus thiab tuaj yeem txiav txim tau qhov tshwm sim ntawm COVID-19 kev kis mob [5 13, 14] ib. Tus kab mob SARS-CoV-2 nkag mus rau hauv lub cev lub hlwb los ntawm ACE2 receptor, thiab tus kab mob no tuaj yeem txo cov kev qhia ntawm ACE2 receptors ntawm ntau lub cev (alveolar cells, nasal mucosa, sab sauv ua pa, endothelium, plawv, lub raum, thiab plab hnyuv) uas ib txwm qhia lawv [5,13,14]. Qhov no tuaj yeem ua rau ACE2 tsub zuj zuj hauv cov hlab ntsws, ua rau lub ntsws raug mob [5]. Cov menyuam mos thiab menyuam yaus uas pom cov ntshav ACE2 siab yuav raug zam los ntawm cov teebmeem no, vim tias lawv cov ntaub so ntswg ACE2 txawv ntawm cov neeg laus [15]. Ntxiv mus, ACE2 qhia kuj ncaj qha ntsig txog cov theem androgen thiab estrogen ntawm cov tib neeg, uas poob rau hnub nyoog [16].
Ob peb lub lis piam tom qab qhov pib ntawm COVID-19 cov tsos mob, cov me nyuam tuaj yeem tsim teeb meem loj: multisystem inflammatory syndrome (MIS; saib hauv qab no, Tshooj 4.3.5). Cov menyuam yaus zoo li muaj lub luag haujlwm tsawg dua hauv kev sib kis ntawm SARS-CoV-2 dua li lawv ua hauv kev kis ntawm lwm cov kab mob. Qhov cuam tshuam txog qhov no yuav tsum tau hais txog thaum txiav txim siab cov txiaj ntsig ntawm kev txhaj tshuaj tiv thaiv menyuam yaus tiv thaiv COVID-19, vim tsawg dua 2 feem pua ntawm cov neeg mob kuaj pom muaj xws li cov menyuam yaus [17–19]. Cov menyuam yaus hnub nyoog qis dua tsib xyoos tsis tshua muaj kev cuam tshuam rau tus kabmob coronavirus ntau dua li cov neeg laus, tab sis lawv kuj tsis muaj kev cuam tshuam rau qhov tshwm sim loj. Yog li ntawd, yog tias yuav tsum tiv thaiv tus kab mob COVID{10}}, kev txhaj tshuaj tiv thaiv menyuam yaus yog ib txoj hauv kev zoo rau lub hom phiaj no [20].
Lub hom phiaj tseem ceeb ntawm qhov kev tshuaj xyuas no yog, ua ntej, qhia qhov sib txawv ntawm lub cev tiv thaiv kab mob tiv thaiv SARS-CoV-2 nyob rau hauv ntau pawg hnub nyoog, txij li thaum yau mus rau cov hluas, piv rau cov laus; thib ob, peb tau saib cov txiaj ntsig thiab qhov teeb meem ntawm COVID-19 ntawm cov pab pawg hnub nyoog sib txawv no txog kev tiv thaiv kab mob. Rau cov laj thawj no, qhov kev tshuaj xyuas no tau muab faib ua plaub pawg loj (Tshooj 2–5), uas tau tham hauv qab no.
2. Kev tshuaj xyuas cov ntaub ntawv thiab kev sib tham
2.1. Kev loj hlob thiab kev loj hlob ntawm lub cev tsis muaj zog
Lub cev tiv thaiv kab mob (IMS) hloov zuj zus los ntawm lub xeev tsis paub tab thaum yug los mus rau lub xeev ntawm kev loj hlob thaum muaj hnub nyoog laus thiab tom qab ntawd poob qis thaum hnub nyoog laus (immunosenescence). Cov txheej txheem kev loj hlob no dhau mus rau ntau theem uas tuaj yeem muab faib ua peb theem muaj hnub nyoog, uas yog lub hauv paus rau kev nkag siab txog kev tiv thaiv kab mob thaum lub sij hawm COVID-19 kev kis kab mob thiab tom qab txhaj tshuaj tiv thaiv.
2.1.1. Thawj theem thaum lub sij hawm Infancy Innate Immunity
Lub luag haujlwm ntawm cov khoom sib txawv ntawm kev tiv thaiv kab mob hauv lub cev tsis muaj zog thaum cev xeeb tub hauv kev sib piv rau cov hnub nyoog tom qab. Cov me nyuam mos muaj kev ua haujlwm tsis zoo ntawm neutrophil, ua rau lawv muaj kev cuam tshuam rau ob qho tib si kis kab mob thiab kab mob, uas tuaj yeem cuam tshuam qhov tsis muaj peev xwm ntawm neutrophil thiab endothelial nplaum ua haujlwm (Table 1) [21–23].
Monocyte-macrophage series kuj qhia tau hais tias txo qis zog thiab tsis zoo tso tawm ntawm bioactive molecules thaum yug los. Txawm hais tias tus naj npawb ntawm pulmonary macrophages raug txo, qhov no raug kho nyob rau ob peb hnub. Tsis tas li ntawd, cov ntshav qaum muaj tsawg dua myeloid dendritic cells (mDCs) dua li cov ntshav peripheral ntawm cov menyuam yaus thiab cov neeg laus. Cov hlwb no qhia tsawg dua costimulatory molecules (HLA-II, CD80, thiab CD86) dua li tus neeg laus mDCs [29]. Ib zaug ntxiv, cov hlwb no tsim tsawg dua IL-12, uas txuas nrog kev tiv thaiv kab mob hauv lub cev nrog kev tiv thaiv kab mob. Yog li ntawd, lub priming ntawm Th1 thiab CD8 hlwb raug cuam tshuam [31]. Lub caij no, cov hlwb no teb rau Toll-like receptor 4 (TLR4) stimulation thiab, yog li, txhawb kev ua haujlwm ntawm Th17 hlwb ntawm proinflammatory cytokine secretion (Table 1).
Natural killer (NK) hlwb, uas yog ib feem ntawm lub cev tiv thaiv kab mob, tsis tshua muaj kev cuam tshuam rau cytokine activation los ntawm IL-12 thiab IL-15 thiab tso tawm tsawg dua gamma interferon, ua rau txo qis cov tshuaj tiv thaiv kab mob [ 32] ib. Tsis tas li ntawd, nyob rau hauv innate caj npab ntawm cov menyuam yug tshiab, NK hlwb muaj kev ua haujlwm tsis txaus, suav nrog cov cell adhesion txo qis vim qhov txo qis hauv selectins, txo TNF ntau lawm, thiab nce hauv inhibitory receptors. Tus naj npawb ntawm cov menyuam yug tshiab PDCs thiab tus nqi ntawm hom I IFN tsim los ntawm cov hlwb no raug txo qis [60]. Qhov sib txawv tseem ceeb ntawm NK hlwb thiab mDCs yog raws li lub tswv yim hais tias cov qub hlwb tau koom nrog autologous kis kab mob los yog cov hlwb tsis zoo nyob rau hauv ib tug tsis-HLA txwv qauv, thaum lub sij hawm tom kawg hlwb koom nrog cov hlwb ntawm cov kab mob sib txawv, xws li cov kab mob kab mob [ 29, 45] ib.
Thaum kawg, lwm txoj hauv kev ntxiv thiab cov lectin-binding activation pathway Cheebtsam, uas kuj yog cov hauv paus kev tiv thaiv kab mob, muaj qhov muaj txiaj ntsig tsawg dua li cov neeg laus, uas ua rau txo qis hauv cov dej num ntxiv, xws li opsonization, lysis ntawm lub hom phiaj hlwb, thiab kev kho kom haum xeeb ntawm cov txheej txheem inflammatory tawm tsam microbial molecules [33]. Yog li ntawd, kev tiv thaiv hauv lub cev rau kev tiv thaiv kev ua ub no yog kev cuam tshuam loj heev tom qab yug me nyuam.
Adaptive Immunity
Adaptive tiv thaiv kuj txawv thaum lub sij hawm me nyuam mos piv nrog rau cov neeg laus. Cov kev sib txawv no suav nrog T thiab B hlwb. Tom qab yug me nyuam, peripheral Treg hlwb (Fox 3- zoo) txuas ntxiv mus [36], ntawm qhov concentration uas yog kwv yees li 3 feem pua ntawm tag nrho CD4 ntxiv rau T hlwb cov pej xeem [35], los kho cov tshuaj tiv thaiv. lus teb [37]. Qhov no tuaj yeem ua rau txo qis kev lees paub ntawm alloantigens, cov lus teb tsis zoo rau cov tshuaj tiv thaiv txawv teb chaws, thiab cov lus teb T-cell skewed rau Th2 kev tiv thaiv. Txawm li cas los xij, txhawm rau them nyiaj rau qhov tsis ua tiav ntawm Th1 ntawm tes ua haujlwm, T hlwb nrog gamma-delta T cell receptors (δ-TCRs) tuaj yeem tsim cov gamma-interferon tseem ceeb tom qab luv luv polyclonal stimulation thaum muaj kab mob neonatal [39,40].
Ntawm qhov tsis sib xws, raws li kev tiv thaiv kab mob humoral, B hlwb muaj ob hom. Ua ntej, muaj B2 hlwb, uas tso tawm qhov tsis tshua muaj kev sib raug zoo IgM tawm tsam cov antigens tsawg, suav nrog cov kab mob polysaccharides, thiab tsim IL-10 thiab hloov pauv kev loj hlob (TGF). Ob yam tom kawg tuaj yeem txhawb nqa Th2 teb [42]. B1 hlwb (cov pa roj ntsha) muaj qhov dav dav ntawm cov lus teb ntawm immunoglobulin nyob rau hauv cov qog ntshav hauv nruab nrab thiab cov pob txha pob txha thiab muaj kwv yees li 40 feem pua ntawm cov ntshav peripheral B hlwb txij thaum yug mus rau ob peb lub hlis tom qab [61].
Tsis tas li ntawd, kev tiv thaiv kev tiv thaiv kab mob rau T cell-dependent antigens hauv neonates muaj qhov cuam tshuam loj heev hauv kev sib piv rau cov menyuam yaus thiab cov neeg laus [43]. Cov ntaub ntawv no muaj feem xyuam rau cov kev pab cuam txhaj tshuaj tiv thaiv cov menyuam mos thiab menyuam mos. Yog li ntawd, vim muaj qhov tsis muaj zog tiv thaiv kab mob hauv lub cev thiab tsis muaj zog Th1 thiab cov tshuaj tiv thaiv kab mob hauv cov menyuam mos, cov neeg tuag ntawm cov menyuam mos los ntawm kev kis rau cov kab mob uas tsis yog SARS-CoV-2 yog siab [49].
Thaum kawg, cov lus teb muaj zog tiv thaiv kab mob yog nyob ntawm qhov muaj peev xwm ntawm DCs kom muaj kev loj hlob nrog rau kev ua kom muaj zog, sib txawv, thiab muaj sia nyob ntawm T thiab B hlwb. Cov menyuam yug tshiab DCs muaj lub peev xwm poob qis los teb rau cov qauv sib txuas nrog cov qauv molecular (PAMPs) ntawm Tus Xov Tooj-zoo li receptors (TLRs) thiab retinoic acid-inducible gene-I-like (RIGI) receptors, ua rau muaj kev cuam tshuam ntawm costimulatory molecules (CD40). , CD, thiab CD86) thiab txo qis ntawm IL-12p70, uas yog qhov tseem ceeb rau kev sib txawv ntawm CD4 Th1 hlwb thiab CD8 ntxiv rau T hlwb. Cov menyuam yug tshiab DCs kuj tseem nthuav tawm IL-4 ntau lawm. CD4 ntxiv rau T cell sib txawv yog skewed mus rau zus tau tej cov Th2 hlwb vim tsis muaj concentration ntawm IL-12p70 thiab ntau lawm ntawm IL-4. Qhov txo qis IL-12p70 concentration cuam tshuam rau CD8 ntxiv rau T cell txoj kev loj hlob, ua rau qis dua IFN ntau lawm (Daim duab 1). Neonates thiab me nyuam mos kuj nthuav tawm cov lus teb Treg. Kuj tseem muaj kev ua haujlwm txawv txav hauv cov menyuam yug tshiab T follicular helper (Tfh) hlwb, suav nrog kev loj hlob tsawg, uas ua rau cov lus teb tsis txaus ntawm cov kab mob hauv nruab nrab thiab txo qis tiam ntawm kev sib raug zoo siab thiab isotype-switched antibodies [60].
2.1.2. Theem Ob: Los ntawm Menyuam Yaus mus rau Kev Hluas - Kev Laus
Hauv cov menyuam yaus, ob qho tib si hauv lub cev thiab kev tiv thaiv kab mob pib loj hlob piv nrog lawv cov qib hauv cov menyuam mos, tab sis lawv tseem raug kev txom nyem los ntawm cov kab mob microbial tseem ceeb. Tsis tas li ntawd, qhov concentration ntawm leej niam immunoglobulin kis tau los ntawm cov placenta thiab los ntawm kev pub niam mis pib poob qis thaum muaj hnub nyoog rau lub hlis [50,51].
Thaum lub sij hawm me nyuam yaus, tus naj npawb ntawm Treg hlwb poob qis, thaum tus naj npawb ntawm cov cim xeeb tseem ceeb Th1, Th2, thiab Th17 cov hlwb nce mus rau qhov sib npaug ntawm CD45R-zoo naïve T hlwb [48]. Qhov kev loj hlob ntawm lub cev muaj zog hauv cov neeg muaj zog tiv thaiv kab mob tuaj yeem muab lub cev nrog cov cuab yeej sib txawv los tiv thaiv kab mob los ntawm kev sib cuam tshuam ntawm cov epitopes ntawm microbes thiab lub cev repertoire ntawm lub cim xeeb T hlwb, txawm tias cov uas lub cev tsis tau raug rau yav dhau los [ 53, 56, 57] ib.
B hlwb qhia cov qauv zoo sib xws ntawm cross-reactivity thiab antibody ntau lawm tawm tsam microbial antigens, xws li stimulation ntawm ntuj hemagglutinin (anti-ABO) ntawm chav kawm IgM los ntawm cov hnyuv [62].
Kev kho mob / cov tsos mob thiab cov kab mob subclinical / asymptomatic tuaj yeem ua rau muaj cov tshuaj tiv thaiv kab mob thiab cov priming ntawm T hlwb [44,63]. Cov kab mob kis kab mob thiab kab mob hauv lub cev tuaj yeem ua rau muaj zog CD4 thiab CD8 T cell teb [64]. Qee zaum, microbial superantigens tuaj yeem ua rau muaj kev txhawb nqa ntau dhau ntawm cov hlwb, ua rau tshem tawm qee qhov clones [44,63,64].
B hlwb nkag mus rau hauv somatic hypermutation, tshwj xeeb tshaj yog nyob rau ntawm qhov chaw kub ntawm thaj chaw sib txawv ntawm immunoglobulin [49,65,66]. Cov txheej txheem no tsis tas yuav tsum muaj rau T hlwb, vim tias tsis tas yuav muaj kev sib raug zoo siab T cell receptors vim tias tsis muaj kev sib raug zoo T cell ua kom zoo dua los ntawm kev ua ntawm costimulatory coreceptors [66]. Ntxiv rau qhov no, HLA genetic polymorphism [67] thiab cov noob tswj kev tiv thaiv kab mob hauv lub cev tuaj yeem ua rau pom kev nyuaj ntawm cov neeg laus tiv thaiv kab mob [44,63].
Thaum lub cev tiv thaiv kab mob, cov plasma hlwb uas tsim cov tshuaj tiv thaiv mus rau cov pob txha pob txha, qhov chaw lawv nyob rau ntau lub sijhawm. Tsis tas li ntawd, tej zaum yuav muaj kev rov tsim dua tshiab ntawm cov hlwb B hauv qhov muaj cov tshuaj tiv thaiv tsis tu ncua thiab T pab hlwb. Particulate antigens tau khaws cia los ntawm cov hlwb follicular dendritic rau xyoo hauv cov qog ntshav [44]. Antigen persistence thiab cross-reactive antigens yuav ua rau muaj sia nyob ntawm cov B hlwb, uas faib thiab zais cov tshuaj tiv thaiv [44,61–63].
Hauv kev xaus, lub cev tiv thaiv kab mob tiv thaiv cov kev hloov ntawm fetal mus rau infantile lub neej. Tom qab ntawd, nws loj tuaj thiab txuas ntxiv thaum muaj hnub nyoog laus thiab tom qab ntawd txo qis thaum lub sij hawm immunosenescence. Cov hlwb nco tau nthuav dav hauv lub cev dhau lub neej. Lub cev tiv thaiv kab mob ntawm cov tib neeg senesced yog proportional rau cov me nyuam mos nrog txo qis cov tshuaj tiv thaiv kab mob los ntawm neutrophils thiab macrophages, txo cov tshuaj tiv thaiv antigen los ntawm cov tshuaj tiv thaiv kab mob, tshwj xeeb tshaj yog cov hlwb dendritic, txo NK tua, thiab muaj kev cuam tshuam ncaj ncees rau kev hloov pauv ntawm lub cev tiv thaiv kab mob. Hauv lwm lo lus, kev tiv thaiv kab mob hauv lub cev thiab B cell, Th1, Th2, thiab Treg cov dej num raug cuam tshuam tag nrho, mus rau qhov sib txawv, nyob rau lub neej. Yog li ntawd, cov tub ntxhais hluas thiab laus lub cev tiv thaiv kab mob tsis muaj txiaj ntsig zoo ntawm kev tiv thaiv kab mob (piv txwv li, kab mob) piv rau cov hluas.
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