初治涂陽肺結(jié)核患者治療期間外周血免疫學(xué)特征研究摘要：目的：探究初治涂陽肺結(jié)核患者治療期間外周血免疫學(xué)的特征，為結(jié)核病的治療提供理論依據(jù)。方法：選取30例初治涂陽肺結(jié)核患者，繼發(fā)性肺結(jié)核患者及肝、腎等重要臟器疾病，白細(xì)胞、淋巴細(xì)胞低于正常水平，免疫功能障礙者、接受免疫抑制劑和高面積化療的患者排除。采用雙抗體夾心ELISA法來檢測患者治療前后的血清HLA-DR、CD4、CD8、IFN-γ、IL-2、IL-10、IL-12等免疫學(xué)指標(biāo)的變化情況。結(jié)果：隨著治療時間的延長，HLA-DR、CD4、CD8、IFN-γ、IL-2、IL-12等指標(biāo)均有所上升，其中CD4/CD8比值在治療后達(dá)到高峰，IL-10在治療后顯著下降。結(jié)論：初始治療期間，初治涂陽肺結(jié)核患者外周血免疫學(xué)特征表現(xiàn)出了一定的炎癥與免疫反應(yīng)，治療過程中，免疫指標(biāo)逐漸恢復(fù)，提示免疫系統(tǒng)在肺結(jié)核治療中具有很重要的保護(hù)作用，為結(jié)核病治療提供了依據(jù)。

關(guān)鍵詞：結(jié)核??；免疫學(xué)；HLA-DR；CD4/CD8比值；IFN-γ；IL-2；IL-10；IL-12

Abstract：Objective:Toexploretheimmunologicalcharacteristicsofperipheralbloodofpatientswithnewlydiagnosedsmear-positivepulmonarytuberculosisduringtreatmentandtoprovidetheoreticalbasisforthetreatmentoftuberculosis.Methods:Thirtypatientswithnewlydiagnosedsmear-positivepulmonarytuberculosiswereselected.Patientswithsecondarypulmonarytuberculosisorwithimportantorgandiseases,suchasliverandkidney,whitebloodcellsandlymphocyteslowerthannormallevels,impairedimmunefunctionorthosereceivingimmunosuppressiveagentsandhighareachemotherapywereexcluded.ThechangesinHLA-DR,CD4,CD8,IFN-γ,IL-2,IL-10,IL-12andotherimmunologicalindicesinthepatient'sserumbeforeandaftertreatmentweredetectedbydoubleantibodysandwichELISA.Results:Withtheextensionoftreatmenttime,HLA-DR,CD4,CD8,IFN-γ,IL-2,IL-12andotherindicatorsincreasedtodifferentdegrees,andtheCD4/CD8ratioreachedthepeakaftertreatment.IL-10decreasedsignificantlyaftertreatment.Conclusion:Duringtheinitialtreatment,peripheralbloodofpatientswithnewlydiagnosedsmear-positivepulmonarytuberculosisshowedcertaininflammatoryandimmuneresponses.Duringthetreatment,theimmuneindicatorsgraduallyrecovered,indicatingthattheimmunesystemplayedanimportantprotectiveroleinthetreatmentoftuberculosis,providingabasisforthetreatmentoftuberculosis.

Keywords:Tuberculosis,Immunology,HLA-DR,CD4/CD8ratio,IFN-γ,IL-2,IL-10,IL-1Tuberculosis(TB)remainsamajorglobalhealthchallenge,affectingmillionsofindividualseachyear.TheimmuneresponsetoTBiscomplex,andseveralfactorscontributetothehost'sabilitytocontroltheinfection.Inthisstudy,theperipheralbloodofpatientsnewlydiagnosedwithsmear-positivepulmonaryTBwasanalyzedtoinvestigatetheimmuneresponseduringtheinitialtreatmentandsubsequentrecovery.

OurresultsrevealedthatpatientswithTBexhibitedasignificantincreaseintheexpressionofHLA-DR,whichisamarkerofimmuneactivation,duringtheinitialtreatmentphase.Thisfindingsuggeststhattheimmunesystemisrespondingtotheinfectionandisattemptingtocontrolit.Additionally,theCD4/CD8ratio,whichisameasureofTcellfunction,waslowerinTBpatientscomparedtohealthycontrols,indicatingimpairedTcellresponses.

Furthermore,wefoundthatthelevelsofIFN-γandIL-2,whicharecytokinesinvolvedintheimmuneresponsetoTB,weresignificantlydecreasedinpatientswithTBduringtheinitialtreatmentphase.However,IL-10,ananti-inflammatorycytokine,wassignificantlyincreased.Thesefindingssuggestthattheimmuneresponseissuppressingpro-inflammatorycytokinesandpromotingananti-inflammatoryresponseduringtheinitialtreatmentphase.

Duringthetreatmentphase,weobservedthattheimmuneindicatorsgraduallyrecovered.TheexpressionofHLA-DRandtheCD4/CD8ratioincreasedtonear-normallevels,indicatingarecoveryofimmunefunction.Additionally,thelevelsofIFN-γandIL-2increased,whilethelevelofIL-10decreased.Thesechangessuggestthattheimmuneresponseisbecomingmoreproficientatcontrollingtheinfectionasthetreatmentprogresses.

Inconclusion,ourstudydemonstratesthattheimmuneresponsetoTBiscomplexanddynamic.Duringtheinitialtreatmentphase,theimmuneresponseischaracterizedbyamixtureofinflammatoryandanti-inflammatorycytokines,withanincreaseinimmuneactivationmarkers.Asthetreatmentprogresses,immunefunctionrecovers,andpro-inflammatoryresponsesdominate.ThesefindingsprovideinsightintotheroleoftheimmunesysteminthetreatmentofTBandmayaidinthedevelopmentofnovelimmunotherapeuticstrategiesFurthermore,itisimportanttonotethattheimmuneresponsetoTBisinfluencedbyvariousfactorssuchasage,HIVstatus,andgenetics.OlderadultsandindividualswithHIVinfectionmayhaveaweakerimmuneresponsetoTB,whichcanresultinmoreseverediseaseandpoorertreatmentoutcomes.Similarly,certaingeneticvariantshavebeenassociatedwithincreasedsusceptibilitytoTBandalteredimmuneresponses.

Inrecentyears,therehasbeengrowinginterestinthedevelopmentofimmunotherapeuticapproachestoaugmenttheimmuneresponsetoTB.Onesuchapproachistheuseofimmunomodulatoryagents,whichcanmodulatethebalancebetweenpro-inflammatoryandanti-inflammatorycytokinesandenhancetheimmuneresponsetoTB.Forinstance,interleukin-2(IL-2),acytokinethatstimulatestheproliferationandactivationofTcells,hasshownpromiseinenhancingimmunefunctioninTBpatients.

Anotherpromisingapproachistheuseofmonoclonalantibodies(mAbs)thattargetspecificimmunepathwaysinvolvedintheimmuneresponsetoTB.Forexample,mAbsthattargettheprogrammeddeath-1(PD-1)pathwayhavebeenshowntoenhanceTcellresponsesandimprovebacterialclearanceinanimalmodelsofTB.

InadditiontoimmunomodulatoryagentsandmAbs,therehasalsobeeninterestindevelopingvaccinesthatcanimproveimmuneresponsestoTB.SeveralTBvaccinesarecurrentlyindevelopment,includingsubunitvaccines,recombinantviralvectors,andwhole-cellvaccines.WhilenovaccinehasyetbeenshowntoprovidecompleteprotectionagainstTB,anumberofcandidatevaccineshaveshownpromisingresultsinearlyclinicaltrials.

Overall,theimmuneresponsetoTBisacomplexanddynamicprocessthatisinfluencedbyarangeoffactors.FurtherresearchisneededtobetterunderstandtheimmuneresponsetoTBandtodevelopnovelimmunotherapeuticapproachesthatcanimprovetreatmentoutcomesandreducetheburdenofTBgloballyInadditiontovaccines,thereareotherapproachesbeingexploredtoimproveTBtreatmentoutcomes.Onepromisingavenueistheuseofimmunotherapy,whichaimstoboosttheimmunesystem'sabilitytofightthebacteriathatcauseTB.Onepotentialimmunotherapyistheuseofmonoclonalantibodies,whichareengineeredtotargetspecificcomponentsoftheimmunesystemorbacteria.StudieshaveshownthatmonoclonalantibodiescanimproveTBoutcomesinanimalmodels,andclinicaltrialsinhumansarecurrentlyunderway.

Anotherapproachistheuseofhost-directedtherapy,whichtargetsthehostratherthanthebacteriathemselves.Host-directedtherapiesaimtoenhancetheimmuneresponseortargetcellularpathwaysthatcanhelpcontroltheinfection.Severalhost-directedtherapiesarecurrentlybeingtested,includingvitaminDsupplementation,whichhasshownsomepromiseinimprovingTBoutcomesincertainpopulations.

Overall,thereisstillmuchtobelearnedabouttheimmuneresponsetoTBandhowtoimprovetreatmentoutcomes.However,recentadvancementsinvaccinedevelopmentandimmunot