Francisella Thiab Antibodies Part 2

4.2. Pib ntawm Immune Responses

Yog tias tus yuam sij rau kev sib txuas ntawm cov khoom sib txuas rau saum npoo ntawm F. tularensis yog qhov tshwm sim ntawm kev cuam tshuam yav dhau los ntawm cov kab mob thiab cov tshuaj tiv thaiv kab mob, ces cov tshuaj tiv thaiv twb cuam tshuam los yog tswj cov kab mob thawj zaug kev cuam tshuam nrog lub tswv tsev cell. Yog tias tsuas yog qhov tseeb thawj tus tswv tsev-cov kab mob sib cuam tshuam raug txiav txim siab, ces isotypes ntawm cov tshuaj tiv thaiv ntuj yuav tswj hwm tus kab mob.

Kev sib raug zoo ntawm cov kab mob thiab kev tiv thaiv kab mob yog ze heev. Thaum peb feem ntau xav txog cov kab mob ua cov kab mob txaus ntshai, tsis yog txhua tus kab mob phem. Hloov pauv, qee cov kab mob zoo thiab pab peb tswj kev tiv thaiv kab mob zoo.

Ua ntej, cov kab mob ua lub luag haujlwm tseem ceeb hauv peb lub plab. Muaj ntau cov kab mob hauv peb cov hnyuv. Ntawm ib sab, lawv tuaj yeem pab peb zom zaub mov, thiab ntawm qhov tod tes, lawv tuaj yeem txhim kho peb txoj kev tiv thaiv. Cov kab mob no cuam tshuam nrog peb lub cev tiv thaiv kab mob los pab peb nrhiav thiab rhuav tshem cov kab mob kom peb noj qab nyob zoo.

Qhov thib ob, qee cov kab mob muaj cov tshuaj tua kab mob uas pab peb tua qee yam kab mob. Piv txwv li, qee cov kab mob lactic acid tuaj yeem pab peb tiv thaiv kab mob khaub thuas, mob khaub thuas, thiab lwm yam kab mob. Cov kab mob no yuav tsim cov tshuaj tua kab mob, uas tuaj yeem cuam tshuam kev loj hlob ntawm cov kab mob phem, ua kom peb txoj kev noj qab haus huv.

Yog li ntawd, peb tsis tuaj yeem suav tag nrho cov kab mob tsis zoo. Peb yuav tsum ua tsaug rau cov kab mob zoo rau peb. Peb yuav tsum tau txhawb txoj kev loj hlob ntawm cov kab mob no los ntawm kev noj zaub mov kom zoo thiab kev ua neej kom txhawb nqa peb txoj kev tiv thaiv.

Hauv kev xaus, kev sib raug zoo ntawm cov kab mob thiab kev tiv thaiv kab mob tseem ceeb heev. Kev nkag siab txog cov kab mob muaj txiaj ntsig thiab yuav ua li cas txhawb lawv txoj kev loj hlob yog qhov tseem ceeb rau peb txoj kev noj qab haus huv. Cia peb koom tes nrog cov kab mob, txhim kho kev sib raug zoo nrog lawv, thiab tswj kev tiv thaiv kab mob zoo. Yog li los ntawm qhov kev xav no, peb yuav tsum txhim kho peb txoj kev tiv thaiv kom tiv thaiv kab mob. Cistanche tuaj yeem txhim kho peb txoj kev tiv thaiv zoo vim tias cov polysaccharides hauv Cistanche tuaj yeem tswj hwm kev tiv thaiv kab mob ntawm tib neeg lub cev thiab txhim kho kev tiv thaiv kab mob hauv lub cev. Kev muaj peev xwm ntxhov siab, txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.

Nyem qhov txiaj ntsig kev noj qab haus huv ntawm cistanche

Qhov kev xav no muaj feem xyuam rau kev faib tawm ntawm cov receptors (CRs) thiab Fc receptors ntawm hom tsiaj ntawm tes. Thaum macrophages thiab monocytes nthuav qhia ntxiv CR1, CR3, thiab CR4 receptors ntawm lawv qhov chaw, follicular dendritic hlwb qhia CR1, CR2, thiab CR3 receptors, thiab B hlwb qhia tsuas yog CR1 thiab CR2 receptors [108]. Ib yam li ntawd, Fc-receptor (FcR) hom rau IgG thiab rau lwm yam hloov pauv Ig isotypes tau tshaj tawm ntawm cov hlwb phagocytic, suav nrog cov neutrophils thiab eosinophil granulocytes, tab sis FcµR khi IgM yog xaiv tsuas yog qhia ntawm T thiab B lymphocytes thiab natural killer (NK). cov hlwb hauv tib neeg thiab tshwj xeeb ntawm B hlwb hauv nas [109,110]. FcµR signaling yog ib qho tseem ceeb tsis yog rau B-cell ciaj sia taus thiab ua kom muaj zog, IgM homeostasis, thiab kev tswj hwm lub cev tiv thaiv kab mob tab sis kuj rau kev daws teeb meem ntawm kev kis kab mob [109,111–113].

Ntuj tshuaj tiv thaiv ntawm IgM isotype yog cov khoom tseem ceeb thaum lub sij hawm thawj kev cuam tshuam ntawm Francisella nrog tib neeg neutrophils thiab macrophages. Ntuj IgM khi rau saum npoo capsular thiab O antigen polysaccharides ntawm F. tularensis thiab activates classical complement cascade ntawm C1q. Qhov ntawd yog ua raws li C3-opsonization ntawm tus kab mob. Francisella opsonized los ntawm C3 complement fragments yog thaum kawg phagocytosed los ntawm tib neeg neutrophils ntawm CR1 thiab CR3 ua yeeb yam hauv kev hais kwv txhiaj thiab los ntawm tib neeg monocyte-derived macrophages ntawm CR3 thiab CR4 [114,115].

Lub IgM nto antigen receptor thiab CR1/2 ntawm B hlwb yog xav tau rau Francisella lub internalization nyob rau hauv lub B hlwb [20]. Yog li, ntuj IgM cov tshuaj tiv thaiv uas opsonize Francisella nto Cheebtsam pib lub classical complement cascade ntawm C1q thiab txhawb lub internalization ntawm Francisella los ntawm txawv complement receptors nyob rau hauv ib tug phagocyte tshwj xeeb yam. Internalization ntawm Francisella rau hauv phagocytic cell yog ib qho yuav tsum tau ua ua ntej rau kev tshaj tawm thiab kev loj hlob ntawm tus kab mob ntawm ib sab thiab kev nthuav qhia antigen rau T lymphocytes ntawm qhov tod tes.

Qhov tseem ceeb ntawm kev ua haujlwm siab B1a hlwb tsim cov tshuaj tiv thaiv IgM ntuj tau pom tias siv µMT-/- nas, uas tsis muaj µ saw hauv B cell txoj kev loj hlob [116]. Cov nas µMT-/-, tsis muaj cov hlwb B paub tab, pom muaj kev cuam tshuam rau thawj tus kab mob nrog LVS, nrog rau txo qis kev tiv thaiv kab mob thib ob thiab muaj kev cuam tshuam ntau dua rau kev kis tus kab mob F. tularensis strain SchuS4, dua li cov nas qus hom [ 117, 118] ib.

Yog li, cov tshuaj tiv thaiv IgM, raws li thawj cov tshuaj tiv thaiv kab mob isotype tshwm sim thaum lub sijhawm hloov pauv, nrog rau thaum lub sijhawm ontogeny, thiab thawj isotype teb rau antigenic stimulation, tej zaum yuav yog tus thawj coj hauv kev tiv thaiv kab mob. Nws tau raug pom, siv tus qauv murine thiab classical qauv immunogens, uas khi ntawm kev sib txuas mus rau IgM antibody tshwj xeeb rau immunogen txhim kho kev humoral tab sis tsis yog T-cell-dependent cellular teb [119]. IgM, zoo ib yam li IgG3, raws li ob qho tib si yog cov tshuaj tiv thaiv kab mob hauv lub cev, tswj cov tshuaj tiv thaiv kab mob los ntawm kev ntxiv thiab cov receptors 1 thiab 2 (CR1/2) qhia ntawm ob lub hlwb B thiab follicular dendritic hlwb [120].

Raws li yav dhau los tau nthuav tawm, Francisella cuam tshuam ncaj qha nrog peritoneal murine B hlwb [18–20,121] thiab, thaum ntxov li 12 teev tom qab kis kab mob, ob qho tib si kab mob tsis muaj kab mob thiab cov nas tsis muaj kab mob tshwj xeeb uas kis tus kab mob F. tularensis tsim cov kab mob-induced antibody clones reacting. nrog F. tularensis proteins thiab muaj cov yam ntxwv ntawm cov tshuaj tiv thaiv ntuj. Raws li cov ntaub ntawv nyob rau hauv cov ntaub ntawv, peb characterized lawv functional profile li inducers ntawm homeostasis restoration (Table 1). Peb kuj hais tias kev tiv thaiv phylogenetically stabilized mechanism siv cov kab mob thaum ntxov-induced antibody tshwj xeeb tuaj yeem ua kom tsis yog tsuas yog tshem tawm cov kab mob xwb tab sis kuj tshem tawm cov khib nyiab thiab cov khoom seem ntawm cov kab mob uas ua rau nws tus kheej puas tsuaj [98].

4.3. Adaptive Immune Teb: Antibody Functions

Antibody functions nyob rau hauv lub moj khaum ntawm lub cev tiv thaiv mechanisms yog teev los ntawm antibody molecule qauv thiab los ntawm cellular antibody receptors, uas xyuas kom meej cov teeb liab transduction thiab cellular teb. Antibody molecules muaj ob lub luag haujlwm ua haujlwm. Lub antigen-binding fragment (Fab) confers antigen tshwj xeeb. Fc fragment (crystallizable fragment), feem ntau hu ua cov seem tas li, tsav lwm yam tshuaj tiv thaiv kab mob. Fc fragment variants, IgM, IgD, IgG, IgA, thiab IgE isotypes, muaj cov yam ntxwv tshwj xeeb uas cuam tshuam rau cov tshuaj tiv thaiv kab mob.

Ntxiv mus, IgG isotype muaj plaub pawg (IgG1, IgG2, IgG3, thiab IgG4) thiab IgA isotype muaj ob pawg (IgA1 thiab IgA2) [122]. Cov kev ua haujlwm tshwj xeeb yog tshwm sim los ntawm kev khi ntawm cov tshuaj tiv thaiv kab mob rau cov receptor tsim nyog ntawm cov xov tooj tshwj xeeb, uas cov tshuaj tiv thaiv Fc domain khi [123,124]. Cov sensors no suav nrog ob qho tib si classical FcRs thiab nonclassical C-type lectin receptors (CLRs), uas tau qhia txawv ntawm cov kab mob hauv lub cev. Lub hom phiaj ntawm kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob yog qhia ntxiv los ntawm kev hloov pauv tom qab hloov pauv ntawm FcRs [125].

Xws li ib tug complex molecular hauv paus ntawm antibody muaj nuj nqi qhia enables teb rau countless molecular thiab cellular lub hom phiaj uas yuav cuam tshuam rau kev ncaj ncees ntawm cov kab mob vertebrate. Yog tias peb lees txais cov kev faib tawm yooj yim ntawm cov tshuaj tiv thaiv kab mob, ces cov tshuaj tiv thaiv muaj peev xwm ntawm kev ua kom tsis zoo ntawm cov kab mob nkag mus rau hauv lub cell thiab nws cov replication, neutralizing microbial virulence yam, xyuas kom meej antigen uptake, inducing antibody-mediated complement activation los yog antibody-dependent cellular cytotoxicity thiab realizing antibody- Nyob ntawm cov cellular phagocytosis, nrog rau cov tshuaj tiv thaiv kab mob nruab nrab granulocyte degranulation thiab tso tawm cov vasoactive mediators, chemoattractants, thiab cytokines. Qhov tsaus ntuj ntawm lawv cov teebmeem tuaj yeem cuam tshuam txog kev tiv thaiv kab mob tiv thaiv kab mob los ntawm kev hloov pauv lub hom phiaj ntawm kev tiv thaiv kab mob [126].

Sib sau ua ke, cov ntaub ntawv tau los ntawm cov qauv sib txawv ntawm F. tularensis kab mob qhia tias cov tshuaj tiv thaiv kab mob tiv thaiv cov qauv ntawm F. tularensis koom nrog ob qho tib si hauv nruab nrab thiab theem hloov ntawm lub cev tiv thaiv kab mob. Cov haujlwm ntawm IgM isotype antibodies uas tsim los ntawm B1a hlwb ua haujlwm thaum lub cev tiv thaiv kab mob hauv lub cev [96,127], thaum lub luag haujlwm ntawm lwm cov isotypes zoo li xav tau thaum lub sijhawm hloov kho ntawm lub cev tiv thaiv kab mob F. tularensis.

Cov txiaj ntsig tau los ntawm kev tshawb fawb los ntawm Furuya et al. qhia tau tias IgA−/− nas muaj kev cuam tshuam ntau dua li IgA ntxiv / ntxiv rau nas rau intranasal F. tularensis LVS kab mob uas tau pib nyob rau lub lim tiam thib ob tom qab kis kab mob, txawm tias txhim kho qib siab dua ntawm cov tshuaj tiv thaiv LVS tag nrho, IgG, thiab IgM isotype antibodies hauv bronchoalveolar lavage [128]

Tsis tas li ntawd, kev sib piv ntawm kev txhaj tshuaj tiv thaiv los ntawm txoj kev sib txawv (intradermal piv rau intranasal) qhia txog kev koom tes ntawm IgA isotype antibodies hauv kev tiv thaiv kev tiv thaiv kev ua rau tuag taus ntawm F. tularensis kab mob [129,130].

Kev tiv thaiv kev ua tau zoo ntawm IgA antibody isotype zoo li koom nrog cov xwm txheej nyuaj uas suav nrog, inter alia, cellular IFN- teb [128]. Kev sim nrog F. tularensis lipopolysaccharide ntxiv tau pom lub luag haujlwm ntawm IgA hauv IgG chav kawm hloov tom qab txhaj tshuaj lipopolysaccharide. Cov nyhuv modulatory no, pom ntawm IgA-/- nas, tuaj yeem kov yeej los ntawm kev txhaj tshuaj tiv thaiv kab mob tag nrho [131].

IgG antibody isotype dominates thaum lub sij hawm yoog teb rau F. tularensis ntuj kab mob (piv txwv li, los ntawm lub lim tiam thib ob tom qab kis kab mob) hauv tib neeg. Qhov kev txiav txim siab zoo li no tau txais kev txhawb nqa los ntawm ntau cov kev tshawb fawb, sib sau ua ke hauv kev tshuaj xyuas los ntawm Maurin li al. [63]. Ntawm cov IgG subclasses, IgG2 subclass tau yeej, tau kuaj pom hauv 92.9 feem pua ​​​​ntawm cov neeg mob uas muaj kev paub tseeb ntawm tularemia.

Cov qib ntshav ntawm IgG2 yeej dhau ntawm cov IgG1 thiab IgG3, thiab theem ntawm IgG4 yog qis dua qib kuaj pom [66]. Cov teebmeem ntawm IgG cov tshuaj tiv thaiv thaum lub sijhawm hloov kho ntawm kev tiv thaiv kab mob feem ntau yog tsim los ntawm receptors rau lawv cov Fc fragments. Kev lees paub ntawm FcR-targeted immunogen muaj qhov cuam tshuam loj rau kev qhia txog kev tiv thaiv kab mob. Lub hom phiaj ntawm qhov inactivated F. tularensis nyob txhaj tshuaj tiv thaiv siv nas IgG2a anti-F. tularensis LPS mAb raws li FcRs ntawm qhov chaw mucosal (ntawm kev txhaj tshuaj intranasal) txhim kho cov tshuaj tiv thaiv kab mob tshwj xeeb IgA thiab muab kev tiv thaiv tiv thaiv kab mob tom ntej hauv IgA-raws li. Tsis tas li ntawd, nws txhim kho kev tiv thaiv tiv thaiv kab mob SchuS4 heev ntawm F. tularensis.

Ob hom FcRs, tshwj xeeb yog FcgammaR thiab FcR neonatal, yog qhov tseem ceeb rau kev tiv thaiv no [132]. Ib qho txiaj ntsig zoo ib yam li induction ntawm kev tiv thaiv teb raws li kev siv opsonized inactivated F. tularensis tau pom tias tshwm sim tom qab kev ywj pheej intranasal daim ntawv thov ntawm IgG2a anti-F. tularensis mAb thiab inactivated F. tularensis nyob txhaj tshuaj tiv thaiv kab mob [133]. Qhov kev tsim qauv no kuj tau pom tias muaj kev nce ntxiv hauv kev tiv thaiv cov kev sib tw F. tularensis tom ntej uas yog FcR-dependent thiab yuav tsum muaj kev sib txuas ntawm lub cev ntawm cov tshuaj tiv thaiv monoclonal thiab inactivated F. tularensis immunogen [133].

Yog lub luag hauj lwm ntawm anti-F. tularensis cov tshuaj tiv thaiv thaum lub sij hawm murine innate theem ntawm lub cev tiv thaiv kab mob feem ntau yog nyob ntawm kev ua kom tiav, tom qab ntawd qhov kev vam khom tsis tau tshwm sim siv sera tau txais thaum lub sij hawm hloov kho ntawm lub cev tiv thaiv kab mob los yog siv convalescent sera. Hauv qhov no, kev tiv thaiv ntawm cov tshuaj tiv thaiv Francisella yog ywj siab ntawm kev ua kom muaj zog ntxiv tab sis qhov kev vam khom ntawm Fc receptors thiab phagocytosis tau tshwm sim [134].

Kev tshawb fawb txog kev sib xyaw ua ke ntawm inactivated F. tularensis immunogen thiab immune sera lossis anti-F. tularensis mAb tau nthuav tawm cov teebmeem modulatory ntawm kev hloov kho lub cev tiv thaiv kab mob, pib los ntawm kev tiv thaiv zoo dua tiv thaiv kev sib tw F. tularensis tom ntej, ntxiv rau nrog rau kev txhim kho kev khi thiab internalization ntawm inactivated F. tularensis los ntawm cov tshuaj tiv thaiv kab mob los ntawm kev koom tes ntawm ntau hom FcR, txhim kho dendritic. cell maturation, ib lub sij hawm ntev dhau los ntawm Ag-tam sim no cov hlwb txhawb cov T hlwb, thiab modulated kinetics ntawm inactivated F. tularensis immunogen thauj los ntawm periphery mus rau lymphoid cov ntaub so ntswg [132–134].

Antibacterial antibody-dependent cell-mediated cytotoxicity (ADCC) yog ib txoj hauv kev tiv thaiv kab mob uas tuaj yeem txwv kev loj hlob ntawm cov kab mob microbial hauv cov kab mob. Downregulation ntawm microbial proliferation yog cuam tshuam los ntawm kev txwv ntawm microbial proliferation nyob rau hauv lub hlwb [135] los yog ncaj qha los ntawm tua cov kab mob dawb [136]. Nyob rau hauv sib piv rau ntxiv, uas kuj lyses lub hom phiaj tab sis tsis xav tau lwm yam cell, ADCC xav tau ib tug effector cell uas dominantly interacts nrog IgG antibodies khi rau saum npoo ntawm lub hom phiaj hlwb. Hauv qhov kev nkag siab no, ADCC, siv cov tshuaj tiv thaiv kab mob ua ib qho tseem ceeb, tsis muaj kev ywj pheej ntawm kev sib txuas. Tus nquag effector cell hauv ADCC yog NK cell qhia txog Fc receptor. Txawm li cas los xij, lwm hom cell xws li macrophages, neutrophils, lossis eosinophils [137], nrog rau lwm cov tshuaj tiv thaiv kab mob, kuj tuaj yeem kho cov kab mob ADCC [138].

NK hlwb uas tsim nyog Fc receptors yuav khi rau cov tshuaj tiv thaiv kab mob thiab yuav tso cov proteins, xws li perforin thiab granzymes, uas ua rau lysis ntawm cov kab mob. Ib qho ntawm cov qauv Francisella, F. novicida ∆fopC, tau tso cai sau cov ntaub ntawv perforin-mediated inhibition ntawm F. tularensis LVS replication hauv macrophages thaum txheeb xyuas cov NK hlwb raws li hom cell tseem ceeb tsim cov perforins [139]. Nov yog ib qho piv txwv uas tiv thaiv F. tularensis antibodies txwv kev loj hlob ntawm cov kab mob hauv lub cev los ntawm ADCC mechanism. Peb cov ntaub ntawv tsis tau tshaj tawm los ntawm xyoo 1980s qhia txog qhov muaj nyob ntawm ADCC-koom haum txwv ntawm F. tularensis proliferation hauv macrophages. Cov kab mob spleen nonadherent cais los ntawm cov nas uas tau txhaj tshuaj 21 hnub tom qab txhaj tshuaj txwv tsis pub muaj tus naj npawb ntawm F. tularensis hauv cov kab lis kev cai ntawm vivo kab mob peritoneal macrophages los ntawm nas naïve, tab sis tsuas yog thaum cov sera los ntawm cov nas txhaj tshuaj tau ntxiv rau cov kab lis kev cai.

4.4. Kev tiv thaiv tus nqi ntawm Anti-F. Tularensis Antibodies

Hauv kev tshawb fawb thaum ntxov, kev koom tes ntawm cov tshuaj tiv thaiv kab mob los tiv thaiv F. tularensis tshwm sim me ntsis tsis meej. Passively kis cov tshuaj tiv thaiv tau pom tias muaj kev tiv thaiv tiv thaiv F. tularensis subsp. holarctic, suav nrog LVS hom, tab sis tsis tawm tsam F. tularensis subsp. tularensis kab mob. Qhov no tau sau tseg feem ntau hauv SCHU S4 tus qauv kab mob. Tam sim no, txawm li cas los xij, tseem muaj kev tsis sib haum xeeb txog kev koom tes ntawm B hlwb ntawm qib molecular los tiv thaiv kev tiv thaiv kab mob F. tularensis.

Ob qho kev tsim cov cytokines cuam tshuam rau kev ua haujlwm ntawm cov hlwb immunocompetent thiab tsim cov tshuaj tiv thaiv kab mob molecules muaj peev xwm ntawm kev hloov pauv cov txheej txheem ntawm kev tiv thaiv kab mob los rau hauv kev xav. Tsis ntev los no, nws tau pom tseeb tias cov tshuaj tiv thaiv tshwj xeeb tiv thaiv F. tularensis siv rau kev txhaj tshuaj tiv thaiv kab mob yog qee qhov muaj peev xwm tiv thaiv kab mob F. tularensis tuag. Cov kev tshawb fawb thaum ntxov uas siv cov tshuaj tiv thaiv kab mob tau qhia txog qhov tsis txaus ntseeg tiv thaiv kev ua haujlwm ntawm cov tshuaj lom neeg ntawm cov ntshav qab zib [140–142]. Cov kev tshawb fawb tom qab tau pom tias kev kis tus kab mob thiab kev txhaj tshuaj tiv thaiv kab mob ua rau lub cev ntev ntev thiab kev tiv thaiv kab mob ntawm tes; Txawm li cas los xij, kev tiv thaiv kev lom zem tau muab kev tiv thaiv tsuas yog tiv thaiv kab mob uas txo qis kev ua phem [143,144].

Vim li no, kev txaus siab tau tig mus rau txoj kev kawm ntawm cell-mediated immunity mechanisms. Thaum lub sijhawm xyoo txhiab xyoo, ntau cov ntawv tshaj tawm tau txhawb kev txaus siab los kawm ntxiv txog kev tiv thaiv kab mob hauv tularemia [145–148]. Cov qauv sib txawv ntawm kev sim tularemia ua rau muaj kev paub txog kev tiv thaiv tus nqi tiv thaiv F. cov tshuaj tiv thaiv tularensis. Kev hloov pauv ntawm kev tiv thaiv kab mob los ntawm cov tshuaj tiv thaiv tshwj xeeb tiv thaiv F. tularensis muab pov thawj ncaj qha tias, vim muaj cov kab mob tshwj xeeb cov tshuaj tiv thaiv, qhov no yuav muaj txiaj ntsig zoo rau tus tswv tsev thaum kis kab mob los ntawm cov kab mob hauv lub cev [149].

Txawm li cas los xij, tsis muaj kev tiv thaiv hauv BALB / c nas tiv thaiv F. tularensis pulmonary kab mob los ntawm kev hloov ntshav los ntawm F. tularensis subsp. holarctic LVS-cov tsiaj tiv thaiv kab mob [150]. Kev hloov pauv ntawm kev tiv thaiv kab mob sera kuj tiv thaiv cov nas uas muaj kab mob tiv thaiv kab mob rau qee yam. Cov nas irradiated los ntawm sublethal gamma irradiation (3Gy) tau tiv thaiv cov tshuaj tua kab mob tsawg ntawm F. tularensis LVS, nrog rau cov tshuaj tiv thaiv thawj Soviet 15, uas yog virulent rau cov nas ntau dua li LVS hom [151]. Cov nyhuv tiv thaiv ntawm cov tshuaj tiv thaiv Francisella yog nyob ntawm IFN-gamma ntau lawm thiab ntawm Fc R-mediated opsonophagocytosis thiab yog ywj siab ntawm kev ua kom tiav. Qhov no yuav qhia txog lub luag haujlwm tseem ceeb ntawm ADCC hauv kev tiv thaiv kev tiv thaiv kab mob F. tularensis [134].

4.5. Secondary Immune Response: B Cells thiab Antibodies

Kev tiv thaiv kab mob tsis zoo ntawm cov nas me me tiv thaiv tus kab mob F. tularensis LVS tseem tiv thaiv cov nas uas muaj sia nyob tus kab mob LVS thawj zaug tiv thaiv cov kev sib tw thib ob nrog cov kab mob phem heev ntawm F. tularensis subsp. tularensis SchS4. Lub caij no, cov nas tsawg tsawg tau muaj sia nyob uas tsuas yog LVS txhaj tshuaj tiv thaiv yam tsis muaj qhov pib hloov pauv ntawm kev tiv thaiv [151,152]. Yog li, thawj zaug kev koom tes ntawm kev tiv thaiv kab mob humoral rau tus kab mob F. tularensis zoo li ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kev tiv thaiv theem nrab. Parenteral intradermal thiab intraperitoneal F. novicida kab mob ntawm cov nas qus los yog B-cell knockout nas tsis muaj kev cuam tshuam rau kev muaj sia nyob tom qab kev sib tw tuag F. novicida, yog li qhia tau tias B hlwb, yog tias tsis muaj tshuaj tiv thaiv kab mob, ua lub luag haujlwm tseem ceeb hauv kev tswj F. . novicida kab mob hauv nas [153]. Cov kev tshawb fawb tau pom tias, hauv kev tsim cov tshuaj tiv thaiv tiv thaiv tularemia, tseem yuav tsum tau muab qhov tseem ceeb rau kev txhawb nqa kev tiv thaiv kab mob, uas koom nrog kev tiv thaiv kab mob. Qhov no yog pov thawj los ntawm kev tshawb fawb nrog cov tshuaj tiv thaiv ua ke uas muaj cov khoom xyaw uas ua rau ob qho tib si humoral thiab cellular ceg ntawm kev tiv thaiv kab mob thiab tiv thaiv kev sib tw ua rau tuag taus thiab intradermal cov nyom nrog cov tsiaj qus F. tularensis hom Schu S4 / hom A / thiab FSC 108 / hom B. / [154].

5. Cov lus xaus

Cov ntaub ntawv sim tau nthuav tawm hauv cov kev tshawb fawb tau hais los saum toj no qhia meej tias cov tshuaj tiv thaiv yuav tsum yog ib feem tseem ceeb ntawm kev tiv thaiv kev tiv thaiv yog tias nws yuav tsum muaj kev tiv thaiv tiag tiag. Kev tiv thaiv tus kab mob F. tularensis yuav tsum muaj ntau yam xwm txheej tsis sib xws. Thaum ntxov zus tau tej cov anti-F. tularensis antibody [98], uas tej zaum yuav yog ib qho kev txhawb nqa ntawm opsonophagocytosis ntawm cov kab mob, yog ib qho ntawm cov xwm txheej tseem ceeb hauv kev ua kom muaj kev tiv thaiv kab mob tiv thaiv kab mob. Qhov thib ob yog kev tiv thaiv kab mob hauv lub cev thiab ua kom muaj kev nthuav qhia antigen. Raws li cov tshuaj tiv thaiv kab mob, cov hlwb dendritic, macrophages, thiab B hlwb tau nruab nrog cov receptors pom cov kab mob cuam tshuam nrog cov qauv molecular uas kho kom haum rau lub cev tiv thaiv kab mob [4]. Lwm qhov txuas hauv kev ua haujlwm ntawm cov xwm txheej uas muab kev tiv thaiv kev tiv thaiv yog kev ua kom lub cev muaj zog uas tshem tawm cov kab mob ntawm cov hlwb thiab cov ntaub so ntswg ntawm tus tswv tsev. Qhov kawg xav tau kev tiv thaiv kev tshwm sim yog tsim kom muaj kev tiv thaiv kab mob. Cov ntaub ntawv muaj qhia tias cov tshuaj tiv thaiv tuaj yeem pib, tswj, lossis ncaj qha kho cov xwm txheej no.

Muaj ntau txoj hauv kev los siv lub peev xwm ntawm cov tshuaj tiv thaiv kab mob los tsim kom muaj txiaj ntsig zoo thiab muaj kev nyab xeeb ntawm kev tiv thaiv kab mob siab heev ntawm F. tularensis. Qhov yooj yim tshaj plaws ntawm cov no yog kev sib xyaw ua ke ntawm kev txhaj tshuaj tiv thaiv kab mob thiab nquag, uas tsis yog tsuas yog tshem tawm cov kev mob tshwm sim ntawm kev txhaj tshuaj tiv thaiv kab mob nyob, tab sis kuj tseem muaj kev tiv thaiv ntau dua rau cov kev sib tw tom ntej. Qhov thib ob yog ib tiam ntawm cov kab mob tshwj xeeb IgM antibody clones tsim los ntawm B1a B hlwb, uas tau pom tias ua rau muaj kev tiv thaiv thaum xav tias kev sib cuam tshuam ntawm cellular thiab humoral immune mechanisms [155], los yog hauv kev npaj cov tshuaj tiv thaiv clones raws li cov kev paub txog B-cell-activating epitopes ntawm F. tularensis proteins [156].

Lwm qhov kev xav tau zoo dua, txoj hauv kev yog tsim kom muaj cov kab mob sib xyaw ua ke lossis cov kab mob tag nrho nrog lub hom phiaj (homing) cov khoom ntawm eukaryotic molecules, xws li Fc fragments ntawm cov tshuaj tiv thaiv kab mob lossis C3 tivthaiv ntxiv, muab kev qhia opsonophagocytosis ntawm tularemic antigens lossis tag nrho cov microbes thiab pib. cov lus teb tiv thaiv tau zoo (saib, piv txwv li, Holland-Tummillo li al. [157].

Txawm li cas los xij, peb yuav tsum rov hais dua ib zaug ntxiv tias, hais txog kev siv tshuaj tiv thaiv kab mob tularemia zoo, peb tseem muaj qhov tsis sib xws hauv peb txoj kev paub txog kev tiv thaiv kab mob, lawv txoj kev sib koom tes thiab lub sij hawm meej thaum lub sij hawm innate thiab adaptive theem ntawm lub cev tiv thaiv kab mob, thiab cov kab mob molecular mechanisms cuam tshuam. nrog induced lub cev tiv thaiv kab mob. Yog li, txawm hais tias muaj ntau yam kev tshawb fawb txog kev sib koom ua ke ntawm kev sib koom ua ke ntawm cov kab mob sib kis ntawm cov cellular thiab molecular, nws tuaj yeem tsim nyog los ua cov kev tshawb fawb ntxiv txog cov txheej txheem ntawm kev tiv thaiv tus kheej kom tshem tawm cov microbe, suav nrog lub luag haujlwm ntawm B hlwb thiab lawv cov khoom.

Tus sau kev koom tes:

Kev Sau Ntawv—kev npaj ua ntej, KK thiab AM Ob tus kws sau ntawv tau pab sib npaug rau txoj haujlwm. Ob tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:

Txoj haujlwm no tau txais nyiaj los ntawm Ministry of Interior ntawm Czech koom pheej, tus lej nyiaj VJ01030003.

Institutional Review Board Statement:

Kev tshuaj xyuas kev ncaj ncees thiab kev pom zoo tau raug zam rau qhov kev tshaj tawm no vim nws yog ib tsab xov xwm sau tseg.

Cov Lus Qhia Txog Kev Pom Zoo:

Tsis siv tau.

Cov ntaub ntawv muaj nyob:

Tsis siv tau.

Kev tsis sib haum xeeb ntawm kev txaus siab:

Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab. Cov nyiaj txiag tsis muaj lub luag haujlwm hauv kev tsim qauv ntawm kev kawm; hauv kev sau, txheeb xyuas, lossis txhais cov ntaub ntawv; hauv kev sau cov ntawv sau, lossis hauv kev txiav txim siab tshaj tawm cov txiaj ntsig.

Cov ntaub ntawv

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