Francisella Thiab Antibodies Part 1

Abstract:

Kev tiv thaiv kab mob rau cov kab mob hauv lub cev yog nyob ntawm qhov ua kom T pab hom 1- nyob ntawm cov txheej txheem. Kev koom tes ntawm B hlwb los tsim kev tiv thaiv kev tiv thaiv tau ntev tau underestimated. Francisella tularensis, suav nrog ntau hom subspecies, muab cov qauv tsim nyog rau kev kawm txog kev tiv thaiv kab mob tiv thaiv kab mob hauv lub cev.

Peb yav dhau los tau qhia tias Francisella kis B hlwb thiab ua rau B-cell subtypes los tsim ntau cytokines thiab nthuav qhia cov cim ua haujlwm. Tsis ntev los no, peb tau sau cov ntaub ntawv thaum ntxov ntawm cov tshuaj tiv thaiv ntuj tsim los ntawm qhov tshwm sim ntawm Francisella kab mob hauv cov nas. Ntawm no, peb sau cov kev paub tam sim no ntawm lub hauv paus thiab tau txais cov lus teb tsis txaus ntseeg uas pib los ntawm Francisella tus kab mob thiab lawv cov kev sib raug zoo nrog lub cev tiv thaiv kab mob.

Intracellular pathogens xa mus rau cov kab mob pathogenic uas tuaj yeem loj hlob thiab tsim dua tshiab hauv cov hlwb thiab ua rau muaj kev puas tsuaj rau cov tswv tsev. Cov kab mob hauv nruab nrog cev muaj xws li cov kab mob, kab mob, pwm, thiab lwm yam. Qhov txawv ntawm lwm cov kab mob, cov kab mob hauv lub cev tuaj yeem khiav tawm ntawm kev tawm tsam thiab tshem tawm ntawm lub cev tiv thaiv kab mob los ntawm ntau cov txheej txheem ingenious, xws li disguising lawv tus kheej li antigens nyob rau saum npoo ntawm cov kab mob, nkag mus rau sab hauv ntawm tus tswv tsev kom tsis txhob muaj kev tawm tsam ntawm lub cev tiv thaiv kab mob, thiab lwm yam.

Txawm li cas los xij, tus tswv tsev cell kuj tseem muaj cov txheej txheem tiv thaiv tshwj xeeb. Piv txwv li, lub cev tiv thaiv kab mob tuaj yeem tsim muaj ntau cov dawb radicals, peroxides, phages, thiab lwm yam, uas tuaj yeem tua cov kab mob thiab tiv thaiv cov kab mob hauv lub cev los ntawm kev sib faib thiab sib kis. Tsis tas li ntawd, cov tswv tsev tseem tuaj yeem tiv thaiv kev kis kab mob los ntawm cov txheej txheem autoimmune, xws li nthuav tawm cov tshuaj tiv thaiv kab mob rau lub cev tiv thaiv kab mob thiab pib cov tshuaj tiv thaiv kab mob tshwj xeeb.

Kev tiv thaiv kab mob thiab kab mob intracellular yog inextricably txuas. Kev tiv thaiv kab mob yog kev tiv thaiv ntawm tus tswv tsev tiv thaiv kev cuam tshuam ntawm ntau yam kab mob, suav nrog ob yam ntawm kev tiv thaiv kab mob tshwj xeeb thiab kev tiv thaiv tshwj xeeb. Tsis zoo li lwm cov kab mob, cov kab mob intracellular loj hlob thiab tsim tawm hauv cov tswv tsev. Yog li ntawd, cov qauv tiv thaiv kab mob tshwj xeeb, cov tshuaj tiv thaiv kab mob tsis zoo, thiab lub cev tsis muaj zog yuav cuam tshuam rau kev muaj sia nyob thiab kev loj hlob ntawm cov kab mob hauv lub cev.

Yog li, lub luag haujlwm ntawm kev tiv thaiv kab mob hauv lub cev yog qhov tseem ceeb heev. Nrog kev pab los ntawm kev tiv thaiv kab mob, cov cell muaj peev xwm tsim tau ntau cov tshuaj tiv thaiv kab mob, cytotoxic T hlwb, thiab lwm yam, los tua cov kab mob, yog li tshem tawm thiab tua cov kab mob intracellular. Nyob rau hauv tus txheej txheem ntawm kev tiv thaiv cov kab mob intracellular, cov kab mob hauv lub cev tuaj yeem tshem tawm cov kab mob, kab mob, thiab lwm yam hauv cov kab mob los ntawm kev tsim cov phagocytes.

Hauv kev xaus, kev sib raug zoo ntawm cov kab mob intracellular thiab kev tiv thaiv kab mob yog sib cais, thiab nrog kev pab ntawm kev tiv thaiv kab mob, peb tuaj yeem tiv thaiv kev hem thawj ntawm intracellular kab mob thiab ua kom peb lub cev noj qab haus huv. Peb yuav tsum ntxiv dag zog rau peb lub cev tiv thaiv kab mob, tswj kev ua neej zoo, ntxiv dag zog rau lub cev, thiab txhim kho peb txoj kev tiv thaiv, tsim kom muaj lub cev muaj zog. Los ntawm qhov kev xav no, peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo, vim tias cov hmoov tshauv nqaij muaj ntau yam khoom siv roj ntsha, xws li polysaccharides, ob lub nceb, Huang Li, thiab lwm yam. Cov khoom no tuaj yeem txhawb kev tiv thaiv kab mob ntau yam ntawm cov hlwb hauv lub cev, ua kom lawv lub cev tiv thaiv kab mob.

Nyem cistanche tubulosa cov txiaj ntsig

Ntsiab lus:

natural tiv thaiv; cov tshuaj tiv thaiv ntuj; B hlwb; Francisella tularensis; intracellular kab mob.

1. Taw qhia

Nyob rau hauv kev mus cuag cov ntsiab lus ntawm kev nkag siab ntawm lub cev tiv thaiv kab mob uas tau pib los ntawm kev kis tus kab mob Francisella thiab lawv txoj kev sib raug zoo nrog lub cev tiv thaiv kab mob, peb ua raws li peb lub ntsiab lus ntawm kev tawm mus rau lub Rau Hli 2007 tshuaj xyuas tsab xov xwm ntawm cov ncauj lus no luam tawm los ntawm Elkins li al. Cov kws sau ntawv sau tag nrho cov ntsiab lus tam sim no ntawm kev paub nyob rau lub sijhawm ntawd hais txog kev sib raug zoo ntawm Francisella microorganisms thiab tus tswv tsev tiv thaiv kab mob raws li tau txais los ntawm cov qauv tsiaj thiab kev kawm txog tib neeg cov kab mob mus txog rau lawv cov convalescence [1]. Kaum ob ntawm kev tshuaj xyuas npog ntau lub ntsiab lus ntawm induction, kev tswj hwm, thiab kev qhia ntawm tus tswv tsev lub cev tiv thaiv kab mob rau Francisella ntawm qib molecular thiab cellular tau luam tawm txij li lub sijhawm ntawd.

Yog li, niaj hnub no muaj kev paub dav dav txog kev paub txog lub cev tsis muaj zog [2–6] thiab kev koom tes ntawm neutrophils [7–9], macrophages [10–13], thiab cov hlwb dendritic [14–17] thaum lub sij hawm ntawm lub cev tiv thaiv kab mob. Txawm li cas los xij, peb tseem muaj qhov sib txawv loj hauv kev nkag siab txog cov txheej txheem thaum Francisella-tus tswv tsev tiv thaiv kab mob sib cuam tshuam, nyob rau hauv B hlwb thiab cov tshuaj tiv thaiv kab mob [18–21] tuaj yeem ua lub luag haujlwm tseem ceeb thaum lub cev tiv thaiv kab mob hauv lub cev, ib yam li nyob rau theem hloov ntawm kev tiv thaiv kab mob rau Francisella. microbes.

Cov yam ntxwv tseem ceeb ntawm Francisella hom muaj xws li lawv muaj peev xwm kis tau ntau yam kab mob, xws li amoebas [22], zuam [23], yoov tshaj cum [24], ntses [25], amphibians [26], thiab noog [27,28] rau ntau hom tsiaj, xws li nas, lagomorphs, carnivores [29], liab [30], thiab tib neeg [31], thiab ua kom tiav lawv lub voj voog rov ua dua nyob rau hauv ntau hom eukaryotic hlwb. Francisella virulence yam tseem ceeb, txoj kev ua neej intracellular ntawm Francisella, thiab nws cov kev cuam tshuam nrog ib tug neeg ntawm tes organelles tseem tsis tau txaus to taub.

Ib yam li ntawd, cov teeb meem hauv kev ua tus yam ntxwv ntawm kev tiv thaiv molecular thiab cellular cov lus teb ntawm cov kab mob kis tawm tsam Francisella yog vim tus cwj pwm ntawm Francisella, uas tsis muaj zog ua rau cov hlwb ntawm lub cev tiv thaiv kab mob hauv lub cev thiab ua rau muaj zog tiv thaiv cov lus teb ntawm tes [32]. Tshwj xeeb, qhov tshwm sim ntawm kev sib raug zoo ntawm Francisella, B hlwb, thiab ntuj thiab nquag induced antibodies tseem sib cav.

Ntawm no, peb sau cov kev paub tsis ntev los no ntawm qhov teeb meem no thiab nthuav tawm peb qhov kev xav txog lub luag haujlwm ntawm cov tshuaj tiv thaiv thaum muaj kev cuam tshuam ntawm Francisella nrog tus tswv tsev cellular thiab molecular system ntawm kev tiv thaiv. Cov ntaub ntawv hais txog cov tshuaj tiv thaiv kab mob tiv thaiv Francisella yog los ntawm ecological thiab epidemiological kev tshawb fawb, cov ntaub ntawv kho mob, kev tshawb fawb kev sim taw qhia raws li Francisella-tus tswv tsev tiv thaiv kab mob sib cuam tshuam thiab kev tshawb fawb mob siab rau kev tsim cov tshuaj tiv thaiv tularemia.

2. Kev sib cuam tshuam ntawm cov tswv nrog Francisella hauv Ntuj Tso Cov Tshuaj Tiv Thaiv Kab Mob Tseem Ceeb

Vim tias tularemia tau nthuav dav thoob plaws sab qaum teb hemisphere, feem ntau cov kev tshawb fawb los ntawm Tebchaws Europe, Asia, thiab North America. Ntau tus tsiaj qus thiab tsiaj hauv tsev, nrog rau tib neeg, nyob hauv qhov chaw foci ntawm tularemia, muaj cov tshuaj tiv thaiv kab mob rau F. tularensis. Seroprevalence ntawm tularemia yog nyob ntawm ob peb feem kaum ntawm ib feem pua ​​​​rau kaum feem pua ​​​​ntawm cov ntsiab lus, nyob ntawm thaj chaw thiab lub caij ntawm kev tshuaj ntsuam. Cov tsiaj qus me me nyob sab Europe (Apodemus flavicollis, Myodes glareolus, Sorex araneus, Apodemus sylvaticus, Apodemus agrarius, Microtus arvalis, thiab ib Talpa europaea) raug ntes ntawm peb thaj chaw hauv Czech koom pheej tau pom tias muaj cov tshuaj tiv thaiv kab mob F. tularensis, thiab qhov tshwm sim ntawm ntau yam. cov tshuaj tiv thaiv tau sib txawv ntawm cov tsiaj thiab poj niam txiv neej [33].

Peb caug-plaub cov ntshav kuaj los ntawm 656 Swedish cov tsiaj qus tsiaj qus thiab scavengers, ntawm lawv cov dais xim av (Ursus arctos), Eurasian lynx (Lynx lynx), raccoon aub (Nyctereutes procyonoides), hma liab (Vulpes vulpes), boar qus (Sus scrofa), hma (Canis lupus), thiab wolverine (Gulo gulo), muaj cov tshuaj tiv thaiv kab mob F. tularensis subsp. hleb [34] Ntau cov hma qus (V. vulpes), raccoon aub (N. procyonoides), thiab cov npua qus (S. scrofa) sau nyob rau ntau thaj chaw ntawm lub teb chaws Yelemees, nrog rau cov dev yos hav zoov, tau zoo rau cov tshuaj tiv thaiv rau F. tularensis [35] — 37]. Kev raug rau cov tsiaj qus thiab cov tsiaj hauv tsev uas qhia txog cov tshuaj tiv thaiv rau F. tularensis tau raug txheeb xyuas tias yog ib qho kev pheej hmoo rau tib neeg hauv European thaj chaw ntawm Qaib Cov Txwv [38,39]. Cov nas tau kawm nyob rau sab hnub poob Iran (Hamadan Province) thiab koom nrog hom tsiaj ntawm Persian jird (Meriones persicus) thiab Libyan jird (Meriones locus) yog tularemia-seropositive thiab tsis pom muaj qhov cuam tshuam nrog brucellosis [40].

Qee cov tsiaj qus hauv Nyij Pooj, suav nrog cov bears dub, tau pom tias muaj seropositive rau F. tularensis antibodies [41,42]. Seroprevalence rau tularemia ntawm cov tsiaj qus kuj tau pom nyob rau hauv ntau qhov chaw ntawm Russia [43-45], Armenia [46], thiab North America. Cov tshuaj tiv thaiv rau Francisella tau kuaj pom hauv hares hauv Ontario, Alberta, thiab Nova Scotia [47–50], snowshoe hares, muskrats, thiab coyotes (Canis latrans) hauv Québec [51], cov dev hauv New Mexico [52], prairie dev hauv Texas [53], tsiaj qus thiab tib neeg hauv Alaska [54], thiab cov squirrels hauv av (Spermophilus beecheyi) hauv Oregon [55].

Feem ntau paub yog kev tshawb fawb txog tularemia ntawm Martha's Vineyard hauv Massachusetts. Skunks thiab raccoons muaj feem ntau seroreactivity, whereas dawb-ko taw nas, paj rwb npuag, mos lwj, nas, thiab dev tsis [56]. Cov neeg ua liaj ua teb mowing nyom ntawm Martha's Vineyard kuj nquag seropositive [57].

Anti-F. tularensis cov tshuaj tiv thaiv kab mob siv rau hauv kev tshawb fawb txog kev kis kab mob thiab ecological ntawm tularemia tau pom tias muaj kev sib kis ntawm tus kab mob etiological ntawm tularemia, uas tseem suav tias yog cov tshuaj lom neeg muaj npe nyob rau hauv qeb A, thiab cov no tuaj yeem ua haujlwm rau kev tiv thaiv tularemia los ntawm kev txheeb xyuas thaj chaw nrog. nce kev pheej hmoo kis mob. Feem ntau, cov tshuaj tiv thaiv kab mob tsuas yog cov pov thawj ntawm kev sib cuag nrog cov microbe vim hais tias kev cog qoob loo los yog kev kuaj PCR tsis zoo.

Ntxiv mus, cov tshuaj tiv thaiv ib tus neeg isotypes thiab lawv qhov tshwj xeeb, uas yooj yim tshawb pom thiab muaj nyob hauv cov ntshav thiab qaub ncaug, yog qhov tseem ceeb tshwj xeeb rau cov hom phiaj no vim tias lawv kuj tseem tuaj yeem ua rau pom keeb kwm ntawm tus kab mob tularemia (kev kis kab mob thaum ntxov-IgM nkaus xwb, tsis tu ncua lub xeev-IgM. thiab IgG, lossis kis tau tshwm sim qee lub sijhawm dhau los-IgG nkaus xwb) hauv cheeb tsam saib xyuas [51,58–62]. Muaj ntau qhov kev sim thiab thev naus laus zis uas tso cai rau kev tshuaj xyuas tularemia tshwj xeeb tshuaj tiv thaiv kab mob, thiab tuaj yeem siv rau hauv kev tshawb fawb ib puag ncig ntuj [63].

3. Humoral Immune Response to Francisella Infection and Vaccination

Feem ntau qhov chaw hauv cov ntaub ntawv hais tias kev tsim cov tshuaj tiv thaiv kab mob tom qab kev kis tus kab mob nrog nyob Francisella culminates thaum lub lim tiam thib ob tom qab kis kab mob. IgM, IgG, thiab IgA isotypes feem ntau tshwm sim ib txhij thaum qhov kev sim agglutination tau siv rau kev ntsuas tshuaj tiv thaiv kab mob hauv thawj lub lim tiam tom qab kis kab mob. IgG thiab IgA antibody isotypes tuaj yeem kuaj pom ua ntej, txawm li cas los xij, siv cov enzyme-linked immunosorbent assay (ELISA) [64,65].

Ib qho kev tshawb fawb tom qab tau hais ntxiv tias, hauv cov qauv kuaj ntshav tau txais los ntawm cov neeg mob uas muaj kev paub tseeb ntawm tularemia, tshwj xeeb IgG2 cov tshuaj tiv thaiv uas muaj feem ntau ntawm IgG isotypes. Cov tshuaj tiv thaiv tshwj xeeb ntawm IgG1 thiab IgG3 tab sis tsis yog IgG4 kuj tseem muaj [66]. Kev txhaj tshuaj ntawm tib neeg cov neeg tuaj yeem pab dawb nrog cov kab mob nyob hauv F. tularensis ua rau muaj kev tiv thaiv kab mob ntev ntev, uas tuaj yeem ua pov thawj pom tau zoo nyob rau lub lim tiam thib ob tom qab txhaj tshuaj tiv thaiv thiab siv sijhawm tsawg kawg mus txog 18 lub hlis tom qab txhaj tshuaj [67]. Kev tsim cov IgM, IgG, thiab IgA isotypes pib ib txhij; tag nrho cov chav kawm immunoglobulin tau kuaj pom txog li 1.5 xyoo tom qab txhaj tshuaj. Lawv cov lus teb nkhaus txawv, txawm li cas los xij, nrog rau qhov sib txawv ntawm IgM Abs peaking ntxov tshaj plaws, lub hlis thib ob tom qab kis kab mob, thiab titer ntawm IgG Abs peaking kawg, kwv yees li plaub lub hlis tom qab txhaj tshuaj.

Qee cov ntaub ntawv tau pom tias cov ntshav agglutinins tawm tsam Francisella tuaj yeem nyob ntev li 25 xyoo tom qab kev kis tus kabmob nrog Francisella [68]. Txawm li cas los xij, kev ntsuam xyuas ntawm kev tiv thaiv kab mob ntawm tes tau txais kev ntseeg ntau dua li qhov kev sim agglutination siv rau kev ntsuam xyuas ntawm cov lus teb humoral [68], vim hais tias cov lus teb ntawm cov xov tooj ntawm tes nyob ntev dua li cov tshuaj tiv thaiv kab mob. Nws kuj tau pom tias cov tshuaj tiv thaiv kab mob antigenic koom nrog hauv cell-mediated thiab humoral immune teb tsis zoo ib yam. Kev txiav txim siab yog lub luag haujlwm rau kev tiv thaiv kab mob qog noj ntshav tau suav nrog hauv ib pawg ntawm cov proteins, qhov kev txiav txim siab ua rau ELISA kev ua haujlwm feem ntau yog cov carbohydrate moiety [69].

Txawm hais tias F. tularensis lipopolysaccharide (LPS) yog ib qho tsis muaj zog tiv thaiv kab mob thiab inducer ntawm humoral lub cev tiv thaiv kab mob [70,71], tib neeg peripheral B hlwb, tab sis tsis murine splenic B hlwb, tsim kuaj pom thiab nce qib IgM tshuaj tiv thaiv lub sijhawm [72] ].

Qhov kev txiav txim siab no ua rau muaj kev xav tias glycoproteins lossis proteins lawv tus kheej, tsis yog LPS, yuav yog lub hom phiaj ntawm cov tshuaj tiv thaiv. Ib txoj hauv kev siv tshuaj tiv thaiv kab mob siv los tshuaj xyuas qhov tshwj xeeb ntawm cov tshuaj tiv thaiv kab mob ntshav qab zib tau los ntawm cov tib neeg uas tau cog lus tularemia lossis los ntawm cov neeg ua haujlwm hauv chaw kuaj mob thiab cov neeg kuaj mob uas tau txhaj tshuaj tiv thaiv ob hom tshuaj tiv thaiv tularemia, ib qho ntawm LPS, qhia meej txog cov hom phiaj ntawm cov tshuaj tiv thaiv. -F. cov tshuaj tiv thaiv tularensis [73]. Cov tshuaj tiv thaiv tau lees paub ntau txog 50 tularemia proteins, tsuas yog 10 ntawm cov uas tsis muaj orthologs lossis analogs hauv eukaryotic hlwb [73].

Ib qho kev tshawb fawb zoo sib xws tau ua los ntawm kev siv New Zeeland dawb luav txhaj tshuaj tiv thaiv kab mob tua hluav taws kub tua F. tularensis nyob tshuaj tiv thaiv kab mob (LVS) qhia 28 F. tularensis LVS immunoreactive proteins, cuaj yam uas tsis tau txheeb xyuas yav dhau los yog kev tiv thaiv kab mob los ntawm murine lossis tib neeg sera [74 ]. Feem ntau ntawm cov tshuaj tiv thaiv-Francisella antibody tshwj xeeb kuj tau txheeb xyuas hauv lwm tus neeg [64,75–77] thiab ntau qhov kev tshawb fawb tsiaj sim [78-80]. Cov naj npawb ntawm anti-F. tularensis antibody tshwj xeeb hauv cov kev tshawb fawb no tsis tseem ceeb npaum li qhov tseeb tias ntau ntawm lawv muaj feem cuam tshuam rau tus tswv tsev cov hom phiaj protein.

Cov kev tshawb fawb ntawm ntau hom tsiaj uas kis los ntawm F. tularensis hom kab mob tau qhia txog qhov sib xws ntawm cov tshuaj tiv thaiv kab mob tsim tawm thaum lub lim tiam thib ob tom qab kis kab mob lossis txhaj tshuaj tiv thaiv, nrog rau kev vam khom loj ntawm cov tshuaj tiv thaiv kev siv tshuaj tiv thaiv kab mob los ntawm kev txhaj tshuaj tiv thaiv kab mob. Qhov kev niaj hnub no tuaj yeem txiav txim siab txog hom kev tiv thaiv kab mob tiv thaiv kab mob thiab muaj cov kabmob ntawm hom kev sim uas yuav tsum tau siv los kuaj xyuas cov tshuaj tiv thaiv [81–85].

Cov yam ntxwv ntawm Francisella-cov tshuaj tiv thaiv tshwj xeeb tsim tawm hauv cov kev tshawb fawb saum toj no tau muab los ntawm cov qauv sau thaum lub sij hawm hloov lub cev tiv thaiv kab mob. Txawm li cas los xij, ntau cov tshuaj tiv thaiv kab mob ntawm IgM, IgG, thiab IgA isotypes muaj nyob rau hauv tib neeg thiab tsiaj sera thiab yog Ameslikas hu ua autoantibodies (NAAbs). Cov NAAbs no yog tsim los ntawm B1 B hlwb, encoded los ntawm germline noob uas tsis muaj, los yog ob peb, somatic kev hloov, thiab lawv tsis undergo affinity maturation nyob rau hauv ib txwm cov neeg [86,87]. Lub hom phiaj ntawm cov NAAbs no yog cov proteins uas tus kheej, txawm tias cov proteins uas kub ntxhov [88], ntxiv cov khoom xyaw [89], interleukins [90], carbohydrates, lossis sialoglycans [91,92].

Cov B1 hlwb no tuaj yeem pom nyob rau hauv pleural thiab peritoneal kab noj hniav, thaum, nyob rau hauv lwm cov ntaub so ntswg, xws li lymph nodes, spleen, los yog pob txha pob txha, qhov feem ntawm B1 hlwb yog heev txwv [93]. B1 hlwb hauv pleural thiab peritoneal kab noj hniav teb rau cov kab mob los ntawm kev ua kom sai, hloov mus rau cov qog nqaij hlav, thiab sib txawv rau hauv cov tshuaj tiv thaiv kab mob zais zis [94]. Tag nrho cov txheej txheem hloov pauv ntawm B1 hlwb rau hauv IgM plasma hlwb yuav siv li 1-1.5 hnub [95]. Kev siv cov kab mob F. tularensis kab mob tus qauv tau qhia tias tsim nyog antigenic stimulation, nyob rau hauv cov ntaub ntawv no los ntawm ib tug glycolipid ntawm F. tularensis LVS, induces IgM thiab IgG B1a antibody teb ua raws li los ntawm kev tsim ntawm ntev-nyob T-ywj siab antigen-specific B1a. nco, ob qho tib si uas muaj cov lus teb sib txawv los ntawm cov canonical B2 humoral tiv thaiv kab mob [96,97].

Yog hais tias cov kab mob peritoneal B1 tuaj rau hauv kev sib cuag ncaj qha nrog F. tularensis strain FSC200, lawv teb tam sim ntawd los ntawm kev tsim cov tshuaj tiv thaiv ntuj, uas peb tau ua ib ntus hu ua kab mob-vim cov tshuaj tiv thaiv ntuj [98]. Lub neej ntev ntawm cov tshuaj tiv thaiv kab mob hauv kev ncig zoo li muaj tsawg heev. Txawm hais tias muaj kev sib kis ntawm cov kab mob thoob plaws hauv lub cev ntawm cov nas uas muaj kab mob, cov spectrum ntawm qhov tshwj xeeb tau pom tias hloov pauv thaum thawj 48 teev tom qab kis kab mob.

Lub hom phiaj rau feem ntau ntawm cov tshuaj tiv thaiv kab mob yog cov kab mob cov kab mob uas muaj orthologs lossis analogs hauv cytosol lossis mitochondria ntawm eukaryotic hlwb [98]. Cov nas tsis muaj kab mob tau teb rau tus kab mob Francisella los ntawm ntau dua titers ntawm tag nrho cov induced antibody isotypes thiab los ntawm ib tug dav spectrum ntawm cov tshuaj tiv thaiv tshwj xeeb tshaj li cov nas tsis muaj kab mob. Nyob rau hauv ob qho tib si, cov nas tau teb feem ntau rau cov proteins phylogenetically conserved nyob rau hauv ob qho tib si prokaryotic thiab eukaryotic hlwb.

Yog li, qhov kom muaj nuj nqis thiab qhov zoo ntawm cov kab mob tshwm sim thaum ntxov uas tshwm sim los ntawm cov tshuaj tiv thaiv kab mob yog nyob ntawm ob qho tib si phylogenetic thiab ontogenetic nco ntawm cov kab mob. Ib qho kev sib cav rau cov txiaj ntsig ntawm phylogenetic nco tuaj yeem tsim tau raws li qhov spectrum ntawm cov tshuaj tiv thaiv kab mob tshwj xeeb cuam tshuam los ntawm kev kis kab mob; ib qho kev sib cav rau ontogenetic nco tuaj yeem ua raws li cov kab mob mus sij hawm ntev-specific nco B1 hlwb tshwm sim los ntawm lub cev tiv thaiv kab mob tam sim ntawd [96–98]. Kev tsim cov hlwb tshwj xeeb rau cov khoom siv microbial thaum lub sij hawm thawj lub cev tiv thaiv kab mob ces nyiam cov lus teb ntawm B1 hlwb rau cov hom phiaj no thaum rov ua dua tshiab thiab, yog li, txwv tsis pub muaj cov tshuaj tiv thaiv ntuj tsim los ntawm thawj kab mob.

Los ntawm tag nrho cov kev xav, yog li ntawd, peb tuaj yeem xav txog qhov kev rov ua dua tshiab hloov qhov kev nyiam ntawm tus kheej / tsis paub txog tus kheej. Thaum lub sij hawm lub ntsiab lus teb, cov lus teb rau tus kheej tsis kis tus kheej dominates kis tsis yog tus kheej. Qhov no suav nrog ob qho tib si tus kheej thiab microbial lub hom phiaj thiab ua kom muaj kev tshem tawm ntawm cov cell tuag. Vim muaj lub cim xeeb ntawm lub hlwb, lub cev tiv thaiv kab mob rau kev rov ua dua tshiab nyiam qhov kev lees paub ntawm tus kab mob tsis yog tus kheej dhau ntawm tus kheej tsis muaj kab mob. Hauv qhov no, kev txwv ntawm microbial proliferation kuj txwv kom muaj nuj nqis ntawm cellular khib nyiab uas yuav tsum tau muab tshem tawm.

4. Lub luag hauj lwm ntawm cov tshuaj tiv thaiv thaum lub sij hawm Innate thiab Adaptive Phase ntawm kev tiv thaiv kab mob

Kev pom zoo hais tias kev tiv thaiv rau Francisella yog kho kom haum xeeb los ntawm T-cell-dependent lub cev tiv thaiv kab mob tau maj mam hloov txij li thaum pib ntawm lub xyoo txhiab. Muaj cov ntaub ntawv tsis lees paub hauv cov ntaub ntawv sau tseg txog kev koom tes ntawm cov tshuaj tiv thaiv kab mob, nrog rau ntawm B-cell subpopulations lawv tus kheej, hauv cov txheej txheem, pib nrog kev cuam tshuam thawj zaug thiab mus txog rau theem ntawm cov lus teb thib ob rau cov kab mob sib tw.

4.1. Francisella thiab Serum Resistance: Lub luag hauj lwm ntawm Complement thiab Antibodies

Cov hom ntawm genus Francisella, nrog rau hom F. tularensis, muaj ntau yam resistant rau cov tshuaj tua kab mob [99]. Cov kev paub txog Francisella kev sib cuam tshuam nrog cov tshuaj ntshav qab zib tseem tseem tsis txaus rau kev nkag siab txog qhov xwm txheej ntawm cov ntshav qab zib. Ob peb hypotheses tau muab tso rau pem hauv ntej. Nws yog feem ntau lees paub tias muaj pes tsawg leeg ntawm F. tularensis LPS O antigen yog ib qho tseem ceeb ua rau F. tularensis tiv thaiv ob qho tib si kev tawm tsam thiab kev cuam tshuam tidal ntawm lwm cov tshuaj lom neeg.

Txawm tias muaj cov qauv sib txawv ntawm F. tularensis subsp. tularensis thiab F. novicida, kev tshawb pom qhia tias O antigens ntawm ob qho tib si F. tularensis subsp. tularensis thiab F. novicida ua lub luag haujlwm hauv kev tiv thaiv los ntawm kev tua cov ntshav qab zib [100–102]. Lub luag haujlwm ntawm O antigen los ntawm F. tularensis subsp. tularensis zoo li me me, txawm li cas los xij, piv rau cov F. novicida O antigen. Qhov sib txawv no yuav qhia tau tias, hauv F. tularensis subsp. tularensis, lwm cov qauv saum npoo, lossis cov khoom siv hauv cov ntshav ua lub luag haujlwm hauv kev tiv thaiv cov ntshav tua [102]. Ib qho ntawm cov no tuaj yeem muaj cov khoom tsis muaj protein ntau ntawm cov txheej txheem sab nraud uas tsis yog LPS thauj los ntawm ValAB, uas yog ib tus tswv cuab ntawm cov neeg tseem ceeb ntawm ABC thauj khoom [103].

Tsis tas li ntawd, qhov tso tawm ntawm qhov tseem ceeb H nrog rau cov ntu iC3b ntawm cov kab mob saum npoo yuav yog lub hauv paus ntsiab lus rau cov ntshav tsis kam ntawm Francisella [104]. Factor H yog ib qho ntawm cov muaj zog soluble inhibitors ntawm kev ntxiv uas, tom qab khi rau lub hom phiaj ntawm cov hlwb lossis cov kab mob microbes, tiv thaiv kev ua kom tiav [105]. Cov ntaub ntawv hauv cov ntaub ntawv tau pom tias ua kom tiav cov khoom seem C3d, iC3b, thiab C4b tau muab tso rau ntawm F. tularensis nto, uas yog ib qho tseem ceeb rau kev ua kom txoj hauv kev classical. Nyob rau hauv sib piv, tsis muaj cov ntaub ntawv nyob rau hauv lub deposition ntawm C5b-C9 membrane nres complex nyob rau saum npoo ntawm Francisella.

Ib qho ntawm cov lus piav qhia vim li cas qhov kev ua kom tiav ntawm qhov ua tiav kev ua tiav los ntawm Francisella tsis tiav thiab ua rau Francisella tiv thaiv kev ua kom tiav lysis tuaj yeem pom hauv lub koom haum (kev khi) ntawm qhov H nrog Francisella nto Cheebtsam. Txawm li cas los xij, kev khi ntawm qhov tseem ceeb H rau F. tularensis nto tsis tau lees paub txaus [106]. Tsis tas li ntawd, kev khi ntawm qee qhov kev tswj hwm cov protein tuaj yeem tiv thaiv kev ua kom ntxiv rau ntawm cov kab mob. Kev khi ntawm vitroectin, uas yog ib qho ntawm cov proteins no, kuj tseem yog lub tshuab uas Francisella strains evade complement attack [99].

Qhov saum npoo ntawm F. tularensis khi cov khoom txuas ntxiv, tab sis cov ntaub ntawv ntawm qhov yuav tsum tau muaj C1q rau kev pom zoo C3 tso tawm qhia qhov tseem ceeb ntawm IgM lossis IgG3 isotypes rau pib khi ntawm cov kab mob nto [107]. Cov lus nug, yog li, yuav tshwm sim seb qhov kev cuam tshuam tseem ceeb ntawm cov kab mob thiab cov khoom siv ntxiv tuaj yeem tshwm sim tom qab kev khi ntuj lossis cov tshuaj tiv thaiv kab mob sib kis ntawm cov kab mob. Yog tias cov tshuaj tiv thaiv zoo li no tsis nyob hauv kev ncig, kev ua kom puv puv puv yuav tsis tuaj, thiab qhov ntawd yuav yog qhov tseem ceeb rau Francisella qhov tsis kam mus rau cov txheej txheem tua ntshav.

Yog li, ib qho kev sib cuam tshuam ntawm Francisella nto Cheebtsam nrog cov tshuaj tiv thaiv kab mob ua kom muaj kev sib txuas ntawm cov khoom sib xyaw ua ke tuaj yeem tsim thawj qhov kev sib koom ua ke ntawm cov tshuaj tiv thaiv kab mob thaum muaj kev sib koom tes ntawm Francisella nrog tus tswv tsev tiv thaiv.

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