Lub Luag Haujlwm ntawm B Cells hauv Lub Cev Tiv Thaiv Kab Mob
Lub cev tiv thaiv kab mob ntawm tib neeg yog ib lub network tiv thaiv uas muaj ntau yam kab mob, cov hlwb, thiab cov molecule uas ua haujlwm ua ke los tiv thaiv lub cev ntawm kev kis kab mob. Ntawm cov khoom tseem ceeb ntawm lub cev no, cov hlwb B (B lymphocytes) ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv "humoral", uas yog, kev tiv thaiv los ntawm cov tshuaj tua kab mob uas ncig hauv cov ntshav thiab cov kua dej hauv lub cev. Cov hlwb B tsis yog tsuas yog tsim cov tshuaj tua kab mob xwb tab sis kuj ua lub luag haujlwm hauv kev nco qab cov kab mob, nthuav tawm cov antigens rau lwm cov hlwb tiv thaiv kab mob, thiab tswj cov lus teb inflammatory. Tsab xov xwm no tham txog lub luag haujlwm ntawm cov hlwb B, los ntawm lawv txoj kev tsim thiab kev ua haujlwm mus rau lawv txoj kev koom tes rau kev noj qab haus huv thiab kab mob.
Cov qe ntshav B yog dab tsi?
Cov qe ntshav B yog ib hom qe ntshav dawb (leukocyte) uas pib hauv cov pob txha. Tsab ntawv "B" txhais tau tias qhov chaw loj hlob hauv tib neeg, uas yog cov pob txha (tsis zoo li cov noog, qhov twg kev loj hlob yog txuam nrog lub bursa ntawm Fabricius). Cov qe ntshav B koom nrog pawg lymphocyte, nrog rau cov qe ntshav T thiab cov qe ntshav tua neeg ntuj (NK). Ib qho tshwj xeeb ntawm cov qe ntshav B yog lawv lub peev xwm los paub txog cov antigens tshwj xeeb los ntawm ib lub receptor tshwj xeeb ntawm lawv qhov chaw hu ua B-cell receptor (BCR).
BCR tso cai rau cov qe ntshav B "paub txog" tej qhov tshwj xeeb ntawm cov kab mob xws li cov kab mob me me, cov kab mob virus, lossis cov tshuaj lom. Thaum cov antigen tsim nyog khi rau BCR, cov qe ntshav B tuaj yeem ua haujlwm thiab tsim mus ua cov qe ntshav plasma tsim cov tshuaj tiv thaiv kab mob lossis cov qe ntshav nco qab ntev.
Kev loj hlob thiab kev loj hlob ntawm B cell
Cov qe ntshav B pib nrog cov qe ntshav hematopoietic stem cell hauv cov pob txha. Cov qe ntshav no ces dhau mus rau theem kev loj hlob, dhau los ua cov qe ntshav pro-B, cov qe ntshav pre-B, thiab tom qab ntawd cov qe ntshav B tsis loj hlob. Thaum lub sijhawm no, ib qho txheej txheem tseem ceeb hu ua V(D)J gene recombination tshwm sim, uas cuam tshuam nrog "randomization" ntawm cov ntu genetic los tsim ib qho BCR tshwj xeeb hauv txhua lub qe ntshav B. Yog li ntawd, lub cev muaj ntau lab tus qe ntshav B sib txawv, txhua tus muaj qhov tshwj xeeb rau cov antigens sib txawv.
Txawm li cas los xij, qhov kev sib txawv no ua rau muaj kev pheej hmoo: qee cov qe ntshav B tuaj yeem paub txog lub cev cov antigens (tus kheej-antigens). Yog li ntawd, cov qe ntshav B tsis tau loj hlob raug xaiv tsis zoo kom tiv thaiv kev tiv thaiv kab mob autoimmunity. Cov qe ntshav B uas muaj kev cuam tshuam ntau dhau rau "tus kheej" tuaj yeem raug tshem tawm (apoptosis), deactivated (anergy), lossis muaj lawv cov receptors hloov kho (receptor editing). Cov qe ntshav B uas dhau kev xaiv yuav tawm hauv cov pob txha thiab mus rau cov kab mob lymphoid theem ob xws li lub spleen thiab cov qog ntshav kom dhau los ua cov qe ntshav B laus.
Kev ua haujlwm ntawm B cell: los ntawm kev paub txog antigen mus rau kev teb zoo
Cov qe ntshav B muaj peev xwm ua haujlwm tau los ntawm ob txoj hauv kev tseem ceeb: kev ua haujlwm nyob ntawm T-cell thiab kev ua haujlwm tsis nyob ntawm T-cell. Qhov sib txawv ntawm ob qho no cuam tshuam rau lub zog, qhov zoo, thiab kev ua haujlwm ntev ntawm lub cev tiv thaiv kab mob.
1. Kev ua haujlwm raws li T
Feem ntau cov teb tiv thaiv kab mob uas muaj zog thiab kav ntev yog kev pab los ntawm cov hlwb T helper, tshwj xeeb yog cov hlwb T follicular (Tfh). Lub tshuab no tau muab sau ua raws li nram no:
1. Kev paub txog cov tshuaj tiv thaiv kab mob: Cov qe ntshav B khi cov tshuaj tiv thaiv kab mob los ntawm BCR.
2. Kev nkag mus rau hauv lub cev thiab kev nthuav qhia ntawm antigen: Cov antigen nkag mus rau hauv B cell, raug ua tiav, thiab nws cov khoom seem raug nthuav tawm ntawm MHC chav kawm II molecules ntawm qhov chaw ntawm B cell.
3. Kev Sib Cuam Tshuam nrog T hlwb: Tfh hlwb paub txog MHC II-antigen complexes ntawm B hlwb thiab muab cov cim pab los ntawm kev sib cuam tshuam molecular (piv txwv li CD40-CD40L) thiab cytokines.
4. Kev loj hlob thiab kev loj hlob ntawm cov lus teb: Cov qe ntshav B loj hlob thiab nkag mus rau hauv qhov chaw loj hlob hauv cov qog ntshav hauv cov qog ntshav.
Hauv qhov chaw germinal, ob txoj kev tseem ceeb tshwm sim: somatic hypermutation (kev hloov pauv hauv cov noob antibody kom ua rau muaj zog khi) thiab class switch recombination (hloov cov chav kawm antibody). Theem no tso cai rau cov antibody uas tshwm sim los ua kom "ntse" thiab ua haujlwm tau zoo.
2. T-ywj pheej ua kom muaj zog
Rau qee cov antigens, xws li polysaccharides ntawm cov tshuaj ntsiav kab mob, B hlwb tuaj yeem ua haujlwm yam tsis muaj kev pab los ntawm T hlwb. Qhov kev teb no feem ntau yog sai dua, tab sis cov tshuaj tiv thaiv kab mob feem ntau yog IgM-dominated, muaj qis dua affinity, thiab lawv lub cim xeeb tsis muaj zog npaum li txoj kev T-dependent. Txawm li cas los xij, txoj kev no tseem ceeb hauv kev tiv thaiv thawj zaug tawm tsam qee cov kab mob, tshwj xeeb tshaj yog ua ntej kev teb hloov pauv tau tsim.
Cov hlwb ntshav: lub cev cov chaw tsim tshuaj tiv thaiv kab mob
Thaum cov qe ntshav B raug ua haujlwm, qee cov yuav hloov mus ua cov qe ntshav plasma. Cov qe ntshav plasma yog cov tshuab tsim cov tshuaj tiv thaiv kab mob uas ua haujlwm heev. Cov tshuaj tiv thaiv kab mob (immunoglobulins) ua haujlwm rau:
- Kev Ua Kom Tsis Muaj Teeb Meem: Khi cov kab mob lossis cov tshuaj lom kom lawv tsis tuaj yeem nkag mus rau hauv cov cell.
– Opsonization: Cim cov kab mob kom yooj yim rau lawv "noj" los ntawm phagocytes xws li macrophages thiab neutrophils.
- Kev ua kom cov protein sib xyaw ua ke: Ua rau muaj ntau cov protein sib xyaw ua ke uas tuaj yeem tho qhov cov kab mob hauv daim nyias nyias lossis ua rau mob ntxiv.
- Kev sib sau ua ke: Ua rau cov kab mob sib sau ua ke kom yooj yim dua los ntxuav.
Cov tshuaj tiv thaiv kab mob muaj ntau pawg tseem ceeb: IgM, IgG, IgA, IgE, thiab IgD. IgM feem ntau tshwm sim thawj zaug thaum pib kis kab mob; IgG feem ntau nyob hauv cov ntshav ncig thiab muaj txiaj ntsig zoo rau kev tiv thaiv mus sij hawm ntev; IgA tseem ceeb rau ntawm cov qhov mucosal xws li txoj hnyuv thiab txoj hlab pa; IgE ua lub luag haujlwm hauv kev ua xua thiab tua cov kab mob; thaum IgD feem ntau ua haujlwm ua tus receptor ntawm cov hlwb B uas tsis tau paub dab tsi.
Cov qe ntshav B nco: lub hauv paus ntawm kev tiv thaiv kab mob mus sij hawm ntev
Ntxiv rau qhov ua cov hlwb ntshav, qee cov hlwb B yuav ua cov hlwb cim xeeb B. Cov hlwb no "nco qab" cov antigens uas tau ntsib yav dhau los thiab tuaj yeem nyob ntev, txawm tias ntau xyoo. Thaum cov kab mob tib yam rov qab los, cov hlwb cim xeeb B tuaj yeem teb sai dua thiab muaj zog dua li qhov teb thawj zaug. Qhov no yog lub hauv paus ntsiab lus tseem ceeb ntawm kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob: lub cev raug tso cai "xyaum" lees paub cov antigens, yog li tsim cov hlwb cim xeeb B thiab cov tshuaj tiv thaiv kab mob yam tsis tas yuav ntsib tus kab mob tiag tiag.
Cov qe ntshav B uas cim xeeb feem ntau muaj kev sib raug zoo thiab kev hloov pauv ntawm cov tshuaj tiv thaiv kab mob. Yog li ntawd, kev kis tus kab mob dua feem ntau tsis hnyav dua lossis tsis muaj tsos mob.
Cov qe ntshav B ua cov neeg nthuav qhia antigen thiab cov neeg tswj hwm kev tiv thaiv kab mob
Lub luag haujlwm ntawm cov qe ntshav B tsis yog txwv rau kev tsim cov tshuaj tiv thaiv kab mob xwb. Cov qe ntshav B kuj tseem tuaj yeem ua haujlwm ua cov qe ntshav uas nthuav tawm antigen (APCs), feem ntau yog los ua kom cov qe ntshav T pab ua haujlwm hauv cov ntsiab lus ntawm cov antigens tshwj xeeb. Los ntawm kev ntes cov antigens los ntawm lawv cov BCRs tshwj xeeb heev, cov qe ntshav B tuaj yeem nthuav tawm cov antigens tau zoo thiab txhawb kev koom tes ntawm cov qe ntshav T thiab cov qe ntshav B.
Tsis tas li ntawd xwb, qee cov qe ntshav B muaj cov haujlwm tswj hwm, feem ntau hu ua cov qe ntshav B tswj hwm (Breg). Cov qe ntshav Breg tsim cov cytokines tiv thaiv kev o xws li IL-10, uas pab tswj cov tshuaj tiv thaiv kab mob ntau dhau. Lub luag haujlwm no yog qhov tseem ceeb rau kev tswj hwm lub cev tiv thaiv kab mob kom sib npaug thiab tiv thaiv lub cev kom tsis txhob tawm tsam nws cov nqaij.
Qhov tseem ceeb ntawm kev kho mob: thaum cov qe ntshav B yog qhov tseem ceeb rau kab mob thiab kev kho mob
Vim lawv lub luag haujlwm tseem ceeb, kev tsis zoo ntawm cov qe ntshav B tuaj yeem ua rau muaj ntau yam teeb meem kev noj qab haus huv.
1. Kev Tiv Thaiv Kab Mob Tsis Zoo: Yog tias cov qe ntshav B tsis ua haujlwm zoo lossis muaj tsawg, lub cev yuav muaj teeb meem tsim cov tshuaj tiv thaiv kab mob. Yog li ntawd, cov neeg mob yuav muaj feem yuav kis tau kab mob ntau zaus, tshwj xeeb yog los ntawm cov kab mob me me.
2. Cov kab mob autoimmune: Cov qe ntshav B uas paub txog lub cev cov antigens tuaj yeem tsim cov autoantibodies thiab ua rau mob o. Piv txwv ntawm cov kab mob uas cuam tshuam nrog cov qe ntshav B suav nrog systemic lupus erythematosus thiab rheumatoid arthritis.
3. Kev Ua Xua: Cov lus teb IgE uas tsim los ntawm cov qe ntshav B tuaj yeem ua rau muaj kev ua xua. Txawm hais tias kev ua xua cuam tshuam nrog ntau lwm cov qe ntshav, xws li cov qe ntshav mast, lub hauv paus ntawm kev tsim IgE tseem txuas nrog kev sib txawv ntawm cov qe ntshav B.
4. Mob qog nqaij hlav B-cell: Qee cov lymphomas thiab leukemias tshwm sim los ntawm kev hloov pauv malignant ntawm B cell, piv txwv li non-Hodgkin's lymphoma, qee cov Hodgkin's lymphomas, thiab chronic lymphocytic leukemia (CLL).
Hauv kev kho mob niaj hnub no, cov qe ntshav B kuj raug tsom rau. Piv txwv li, cov tshuaj tiv thaiv kab mob CD20 monoclonal (xws li rituximab) yog siv los tswj cov qe ntshav B hauv ntau yam kab mob autoimmune thiab mob qog nqaij hlav B. Lub caij no, cov thev naus laus zis tiv thaiv kab mob tseem raug tsim los ua kom zoo tshaj plaws ntawm kev tsim cov qe ntshav B nco thiab cov tshuaj tiv thaiv kab mob muaj zog.
Xaus
Cov qe ntshav B yog lub hauv paus tseem ceeb ntawm lub cev tiv thaiv kab mob los ntawm kev tsim cov tshuaj tiv thaiv kab mob, kev tsim cov cim xeeb ntawm kev tiv thaiv kab mob, kev nthuav qhia antigen, thiab kev tswj hwm kev teb ntawm lub cev tiv thaiv kab mob. Nrog rau lub peev xwm los paub txog cov antigens thiab tsim cov tshuaj tiv thaiv kab mob zoo dua los ntawm kev loj hlob thiab kev hloov pauv chav kawm, cov qe ntshav B ua rau lub cev muaj peev xwm tawm tsam cov kab mob thiab muab kev tiv thaiv mus sij hawm ntev. Kev nkag siab txog cov qe ntshav B tsis yog tsuas yog qhov tseem ceeb hauv kev tshawb fawb xwb tab sis kuj tseem ceeb heev hauv ntiaj teb kev kho mob - los ntawm kev txhaj tshuaj tiv thaiv thiab kev tswj hwm kev ua xua rau cov kab mob autoimmune mus rau kev kho mob qog noj ntshav. Los ntawm kev tshawb fawb hloov pauv, kev siv cov qe ntshav B ua lub hom phiaj kho mob thiab cov khoom tseem ceeb ntawm kev txhaj tshuaj tiv thaiv kab mob yuav ua rau tib neeg muaj zog ntxiv los tawm tsam ntau yam kab mob sib kis thiab tsis sib kis.
