Udindo wa Maselo a B mu Chitetezo cha Mthupi
Chitetezo cha mthupi cha munthu ndi njira yodzitetezera yovuta yopangidwa ndi ziwalo zosiyanasiyana, maselo, ndi mamolekyu osiyanasiyana omwe amagwira ntchito limodzi kuti ateteze thupi ku matenda. Pakati pa zinthu zofunika kwambiri pa dongosololi, maselo a B (ma lymphocyte a B) amachita gawo lalikulu pa chitetezo cha "nthabwala", kutanthauza chitetezo chomwe chimayendetsedwa ndi ma antibodies omwe amayendayenda m'magazi ndi madzi amthupi. Maselo a B samangopanga ma antibodies komanso amachita gawo lokumbukira tizilombo toyambitsa matenda, kupereka ma antigen ku maselo ena odziteteza, komanso kuwongolera mayankho otupa. Nkhaniyi ikufotokoza mokwanira za ntchito ya maselo a B, kuyambira pakupanga kwawo ndi kuyambika kwawo mpaka kuthandiza kwawo pa thanzi ndi matenda.
Kodi maselo a B ndi chiyani?
Maselo a B ndi mtundu wa maselo oyera a m'magazi (leukocyte) omwe amachokera mu fupa la mafupa. Chilembo "B" chimatanthauza malo okhwima mwa anthu, omwe ndi fupa la mafupa (mosiyana ndi mbalame, komwe kukhwima kumagwirizanitsidwa ndi bursa ya Fabricius). Maselo a B ali m'gulu la lymphocyte, pamodzi ndi maselo a T ndi maselo akupha zachilengedwe (NK). Khalidwe losiyana la maselo a B ndi kuthekera kwawo kuzindikira ma antigen enaake kudzera mu cholandirira chapadera pamwamba pawo chotchedwa B-cell receptor (BCR).
BCR imalola maselo a B "kuzindikira" magawo enaake a tizilombo toyambitsa matenda monga mabakiteriya, mavairasi, kapena poizoni. Pamene antigen yoyenera ilumikizana ndi BCR, maselo a B amatha kuyatsidwa ndikukhala selo la plasma lopanga ma antibodies kapena selo lokumbukira lokhalitsa.
Kukula ndi kukhwima kwa maselo a B
Ulendo wa maselo a B umayamba ndi maselo oyambira a hematopoietic mu fupa la mafupa. Maselo amenewa amapita ku magawo okukula, kukhala maselo a pro-B, maselo a pre-B, kenako maselo a B osakhwima. Mu gawoli, njira yofunika kwambiri yotchedwa V(D)J gene recombination imachitika, yomwe imaphatikizapo "randomization" ya magawo a majini kuti apange BCR yapadera mu selo lililonse la B. Zotsatira zake, thupi limakhala ndi mitundu yambiri ya maselo a B, iliyonse yokhala ndi ma antigen osiyanasiyana.
Komabe, kusiyanasiyana kumeneku kumabweretsa chiopsezo: maselo ena a B amatha kuzindikira ma antigen a thupi (self-antigens). Chifukwa chake, maselo a B osakhwima amasankhidwa kuti ateteze chitetezo chamthupi. Maselo a B omwe amakhudzidwa kwambiri ndi "iwo" amatha kuchotsedwa (apoptosis), kutsekedwa (anergy), kapena kusinthidwa kwa ma receptor awo (receptor editing). Maselo a B omwe amadutsa kusankha amachoka mu fupa la mafupa ndikupita ku ziwalo zachiwiri za lymphoid monga ndulu ndi ma lymph nodes kuti akhale maselo a B okhwima.
Kuyambitsa maselo a B: kuyambira kuzindikira ma antigen mpaka kuyankha kogwira mtima
Maselo a B amatha kuyatsidwa kudzera m'njira ziwiri zazikulu: kuyatsidwa komwe kumadalira maselo a T ndi kuyatsidwa komwe kumadalira maselo a T. Kusiyana pakati pa awiriwa kumakhudza mphamvu, ubwino, ndi kulimba kwa chitetezo chamthupi.
1. Kuyambitsa kodalira T
Mayankho amphamvu komanso okhalitsa a chitetezo chamthupi amakhudza thandizo la maselo othandizira a T, makamaka maselo a follicular T (Tfh). Njirayi yafotokozedwa motere:
1. Kuzindikira ma antigen: Maselo a B amamanga ma antigen kudzera mu BCR.
2. Kuika mkati ndi kuwonetsa kwa antigen: Antigen imalowa mu selo B, imakonzedwa, kenako zidutswa zake zimawonetsedwa pa mamolekyu a MHC class II pamwamba pa selo B.
3. Kuyanjana ndi maselo a T: Maselo a Tfh amazindikira ma MHC II-antigen complexes pa maselo a B ndipo amapereka zizindikiro zothandizira kudzera mu kuyanjana kwa mamolekyulu (monga CD40-CD40L) ndi ma cytokines.
4. Kuchulukana ndi kukhwima kwa yankho: Maselo a B amachulukana ndikulowa pakati pa germinal mu lymph node follicle.
Pakati pa germinal, njira ziwiri zofunika kwambiri zimachitika: somatic hypermutation (kusinthika kwa majini a antibody kuti awonjezere mphamvu yomangirira) ndi class switch recombination (kusintha magulu a antibody). Gawoli limalola ma antibodies omwe amabwera kukhala "akuthwa" komanso ogwira ntchito kwambiri.
2. Kuyambitsa kosadalira T
Kwa ma antigen ena, monga ma polysaccharides omwe ali pa makapisozi a bakiteriya, maselo a B amatha kuyatsidwa popanda thandizo la maselo a T. Kuyankha kumeneku nthawi zambiri kumakhala kofulumira, koma ma antibodies nthawi zambiri amakhala ndi IgM-controlled, amakhala ndi mphamvu yochepa, ndipo kukumbukira kwawo kwa chitetezo chamthupi sikolimba ngati njira yodalira T. Komabe, njira iyi ndi yofunika kwambiri poteteza mabakiteriya ena, makamaka asanayambe kuyankha kokhwima kosinthika.
Maselo a plasma: mafakitale a ma antibodies a thupi
Maselo a B akayamba kugwira ntchito, ena amasiyana kukhala maselo a plasma. Maselo a plasma ndi makina opanga ma antibodies amphamvu kwambiri. Ma antibodies (immunoglobulins) amagwira ntchito:
- Kuletsa: Kumangirira mavairasi kapena poizoni kuti asalowe m'maselo.
– Kuzindikira: Kulemba zizindikiro za tizilombo toyambitsa matenda kuti zikhale zosavuta “kudya” ndi ma phagocyte monga macrophages ndi neutrophils.
– Kuyambitsa ntchito yowonjezera: Kumayambitsa mapuloteni angapo othandizira omwe amatha kuboola nembanemba ya mabakiteriya kapena kuwonjezera kutupa.
- Kusakaniza: Kumaphatikiza tizilombo toyambitsa matenda kuti zikhale zosavuta kuyeretsa.
Ma antibodies amapezeka m'magulu angapo akuluakulu: IgM, IgG, IgA, IgE, ndi IgD. IgM nthawi zambiri imawonekera koyamba panthawi yoyamba ya matenda; IgG imayenda bwino kwambiri m'magazi ndipo imagwira ntchito bwino poteteza thupi kwa nthawi yayitali; IgA ndi yofunika kwambiri pamalo a mucous monga m'matumbo ndi m'njira yopumira; IgE imagwira ntchito poyankha ziwengo komanso polimbana ndi tizilombo toyambitsa matenda; pomwe IgD imagwira ntchito makamaka ngati cholandirira maselo a B opanda chidziwitso.
Maselo a Memory B: maziko a chitetezo chamthupi cha nthawi yayitali
Kuwonjezera pa kukhala maselo a plasma, maselo ena a B adzakhala maselo a memory B. Maselo amenewa "amakumbukira" ma antigen omwe adakumana nawo kale ndipo amatha kukhalapo kwa nthawi yayitali, ngakhale zaka zambiri. Pamene tizilombo toyambitsa matenda tomwe timayambitsanso kachilomboka, maselo a memory B amatha kuyankha mwachangu komanso mwamphamvu kuposa momwe adayankhira poyamba. Ichi ndiye mfundo yofunikira pakugwira ntchito bwino kwa katemera: thupi limaloledwa "kuchita" kuzindikira ma antigen, motero kupanga maselo a memory B ndi ma antibodies oteteza popanda kukumana ndi matenda enieni.
Maselo a Memory B nthawi zambiri amakhala ndi mphamvu yowonjezereka komanso kusintha kwa ma antibodies. Chifukwa chake, kubwereranso kwa kachilombo nthawi zambiri kumakhala kofatsa kapena kopanda zizindikiro.
Maselo a B monga opereka ma antigen ndi owongolera mayankho a chitetezo chamthupi
Ntchito ya maselo a B si yokhudza kupanga ma antibodies okha. Maselo a B amathanso kugwira ntchito ngati maselo opereka ma antigen (APCs), makamaka kuti ayambitse maselo a T othandizira pankhani ya ma antigen enaake. Mwa kugwira ma antigen kudzera mu ma BCR awo apadera, maselo a B amatha kupereka ma antigen bwino ndikulimbitsa mgwirizano pakati pa maselo a T ndi maselo a B.
Kuphatikiza apo, magulu ena a maselo a B ali ndi ntchito zowongolera, zomwe nthawi zambiri zimatchedwa maselo a B owongolera (Breg). Maselo a Breg amapanga ma cytokines oletsa kutupa monga IL-10, omwe amathandiza kuletsa machitidwe ochulukirapo a chitetezo chamthupi. Ntchito imeneyi ndi yofunika kwambiri kuti chitetezo chamthupi chikhale bwino komanso kuti thupi lisaukire minofu yake.
Kufunika kwachipatala: pamene maselo a B ndi ofunikira pa matenda ndi chithandizo
Chifukwa cha ntchito yawo yaikulu, matenda a maselo a B angayambitse mavuto osiyanasiyana azaumoyo.
1. Kusowa kwa chitetezo chamthupi: Ngati maselo a B sakugwira ntchito bwino kapena ali ochepa, thupi limakhala ndi vuto lopanga ma antibodies. Chifukwa cha zimenezi, odwala matendawa amakhala pachiwopsezo chotenga matenda mobwerezabwereza, makamaka ochokera ku mabakiteriya.
2. Matenda a Autoimmune: Maselo a B omwe amazindikira ma antigen a thupi amatha kupanga ma autoantibodies ndikuwonjezera kutupa. Zitsanzo za matenda okhudzana ndi maselo a B ndi monga systemic lupus erythematosus ndi rheumatoid arthritis.
3. Ziwengo: Yankho la IgE lomwe limapangidwa ndi maselo a B lingayambitse ziwengo. Ngakhale kuti ziwengo zimakhudza maselo ena ambiri, monga maselo a mast, muzu wa kupanga IgE umagwirizanitsidwa ndi kusiyana kwa maselo a B.
4. Khansa ya maselo a B: Ma lymphoma ndi ma leukemia ena amachokera ku kusintha kwa maselo a B, mwachitsanzo non-Hodgkin's lymphoma, ma lymphoma ena a Hodgkin's, ndi chronic lymphocytic leukemia (CLL).
Mu njira zamakono zochiritsira, maselo a B amathandizidwanso. Mwachitsanzo, ma antibodies a anti-CD20 monoclonal (monga rituximab) amagwiritsidwa ntchito kuletsa maselo a B m'matenda angapo a autoimmune ndi khansa ya maselo a B. Pakadali pano, ukadaulo wa katemera ukupitilira kupangidwa kuti upangitse bwino mapangidwe a maselo a B okumbukira komanso ma antibodies amphamvu oletsa kufalikira kwa maselo.
Mapeto
Maselo a B ndi chinsinsi chofunikira kwambiri cha chitetezo chamthupi chosinthika kudzera mu kupanga ma antibodies, kupanga kukumbukira kwa chitetezo chamthupi, kuwonetsa ma antigen, ndikuwongolera momwe chitetezo chamthupi chimayankhira. Pokhala ndi kuthekera kozindikira ma antigen ndikupanga ma antibodies ogwira ntchito kwambiri kudzera mu kukula kwa affinity ndi kusinthana kwa magulu, maselo a B amathandiza thupi kumenyana bwino ndi tizilombo toyambitsa matenda ndikupereka chitetezo cha nthawi yayitali. Kumvetsetsa maselo a B sikuti ndikofunikira kokha mu biology yoyambira komanso ndikofunikira kwambiri m'dziko lachipatala - kuyambira katemera ndi kasamalidwe ka ziwengo mpaka matenda odziteteza ku matenda a autoimmune mpaka chithandizo cha khansa. Kudzera mu kafukufuku wopita patsogolo, kugwiritsa ntchito maselo a B ngati njira zochiritsira komanso zigawo zazikulu za katemera kudzalimbitsa kwambiri khama la anthu polimbana ndi matenda osiyanasiyana opatsirana komanso osapatsirana.