Njira Zambiri Zofunikira Kuteteza, Kuthetsa Matenda
Mbiri ya chitukuko cha katemera wa HIV yakhala ndi zovuta zambiri ndi zokhumudwitsa, ndipo aliyense amawonetsa kuti "kupambana" kukubweretsanso mavuto ndi mavuto omwe angapambane. Kawirikawiri zimawoneka kuti pa sitepe imodzi yopita patsogolo kafukufuku, chovuta chosayembekezereka chimawabwezeretsanso chimodzi kapena ziwiri.
Mu njira zina, ndiyeso yabwino, popeza sitidayang'anenso ndi woyenera katemera.
Komabe, asayansi akhala akuchita zochuluka kwambiri m'zaka zaposachedwapa, akudziŵa zambiri za mphamvu zovuta za kachirombo ka HIV ndi momwe thupi limayankhira ku matendawa. Chochititsa chidwi kwambiri ndi kupita patsogolo kumene ena amakhulupirira kuti katemera akhoza kuchitika m'zaka 15 zotsatira (pakati pawo, wolemba mwayi wa Nobel Prize and HIV-discoverr Françoise Barré-Sinoussi ).
Ngati katemera woterewo angakhale wotsika mtengo, wotetezeka, ndi wosavuta kupereka ndi kugaŵira malo okhala padziko lonse kuti awoneke. Koma zomwe timadziwa ndikudziwa kuti zingapo zing'onozing'ono zidzakonzekera ngati wina aliyense wodzisankhira adzasunthirapo pambali pazomwe amakhulupirira.
Njira 3 zomwe HIV imayendera katemera
Kuchokera ku lingaliro lofunika kwambiri, kuyesetsa kukhazikitsa kachilombo ka HIV kwalepheretsedwa ndi mitundu yosiyanasiyana ya kachilomboka. Kupititsa patsogolo kachilombo ka HIV sikungowonjezereka (maola oposa 24) koma kumakhala zolakwa zosavuta, kusinthanso mavoti omwe amachititsa kuti kachilombo ka HIV kamangidwe kuchokera kwa wina ndi mnzake.
Kukhazikitsa katemera mmodzi omwe amatha kuthetsa mavuto oposa 60 omwe amachititsa kuti matendawa asokonezeke komanso kuchulukana kwa mitundu yambiri yapamtunda-komanso padziko lonse lapansi-kumakhala kovuta kwambiri pamene katemera wathanzi ungateteze ku chiwerengero chochepa cha mavitamini.
Chachiwiri, kumenyana ndi HIV kumafuna kuchitapo kanthu mwamphamvu kuchokera ku chitetezo cha mthupi, ndipo izi ndizo momwe zidalephereka.
Mwachikhalidwe, maselo oyera amagazi oyera omwe amatchedwa CD4 T-maselo amayambitsa yankho mwa kuwonetsera maselo opha ku malo omwe ali ndi kachilomboka. Zodabwitsa, izi ndi maselo omwe HIV imayambitsa matenda. Pochita zimenezi, kachilombo ka HIV kamapangitsa kuti thupi likhale lotha kudzitetezera pamene CD4 ya anthu imatha kuthetsedwa, zomwe zimachititsa kuti chitetezo chakumapeto chitetezedwe ku chitetezo cha thupi chimathere .
Potsirizira pake, kuthetseratu kachilombo ka HIV kumatetezedwa ndi kachilombo ka HIV kuti athe kubisala ku chitetezo cha mthupi. Pasanapite kachilombo, pamene kachilombo ka HIV kakuyenda momasuka m'magazi, kachilombo kamene kamatchedwa ( provirus ) kamalowa mu malo osungirako ma selo (omwe amatchedwa malo osungira ). Mukalowa mkati mwa maselowa, HIV imatetezedwa kuti musadziwe. M'malo mowopsa ndi kupha selo lolandiridwa, kachilombo ka HIV kamangopatukana kokha pamodzi ndi mchereyo. Izi zikutanthauza kuti ngakhale kutuluka kwaufulu kachilombo ka HIV kumathetsedwa, kachilombo ka "kobisika" kamene kangathe kuchitapo kanthu ndikuyambitsa matenda atsopano.
Zolepheretsa Kugonjetsa
Zakhala zikuonekeratu m'zaka zaposachedwapa kuti kuthana ndi zovutazi kudzafuna njira yowonjezera yambiri komanso kuti njira imodzi yokha idzakhala yosakwaniritsira zolinga zofunikira popanga katemera wowononga.
Izi zikuluzikulu za njirayi ziyenera kutero:
- Njira zothetsera mavuto ambirimbiri a HIV
- Njira zothandizira kuti chitetezo cha mthupi chitetezeke
- njira zotetezera kukhulupirika kwa chitetezo cha mthupi
- Njira zothetsera ndi kupha mavairasi osayenerera
Kupita patsogolo kumapangidwa pazinthu zambiri zomwe akukonzekera, mothandizidwa mosiyanasiyana ndi bwino, ndipo akhoza kutanthauzidwa motere:
Kulimbikitsa "Kutetezedwa Kwambiri" Kuteteza Mthupi
Pakati pa anthu omwe ali ndi kachilombo ka HIV, pali chigawo cha anthu omwe amadziwika kuti olamulira akuluakulu (ECs) omwe amawoneka kuti ali ndi kachilombo ka HIV .
Zaka zaposachedwapa, asayansi ayamba kuzindikira zamoyo zomwe zasinthika zomwe amakhulupirira kuti zimapereka yankho lachilengedwe, loteteza. Zina mwazo ndi mapuloteni apadera otetezera omwe amadziwika kuti amateteza kwambiri ma antibodies (kapena mabBbs) .
Ma antibodies amatetezera thupi motsutsana ndi wodwala wodwala matenda (pathogen). Ambiri ndi omwe amachititsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda. Mosiyana ndi zimenezi, bNAbs imatha kupha mitundu yambiri ya HIV - mpaka 90% pazochitika zina-potero zimachepetsa "kachilombo ka HIV" kuti katenge ndi kufalikira.
Pakalipano, asayansi sakuzindikira njira zabwino zothandizira kuyankha kwa bNAb kumalo omwe angatetezedwe kukhala oteteza, ndipo kuti kuyankha koteroko kungatenge miyezi kapena zaka kuti zikule. Kulimbana ndi zovuta kwambiri ndikuti sitikudziŵa ngati kukakamizidwa kwa mabBB kungakhale kovulaza-kaya atachita maselo a thupi ndipo amalephera kulandira chithandizo chilichonse.
Pomwe zikunenedwa, zowonjezereka zimayikidwa pazinthu zowonongeka za bNA mabungwe omwe ali ndi kachilombo ka HIV. Mmodzi wa bNAb, wotchedwa 3BNC117, amapezeka osati kuteteza kachilombo ka maselo atsopano komanso kuchotsa maselo omwe ali ndi HIV. Njira imeneyi nthawi zina ingalole njira yowonjezera kapena yothandizira anthu omwe ali ndi kachilombo ka HIV.
Kusunga kapena Kubwezeretsa Umphumphu Wosadziwika
Ngakhale asayansi atatha kupanga bwino bnAbs, zikhoza kukhala ndi mphamvu yowonongeka ya mthupi. Izi zimaonedwa kuti ndizovuta kwambiri monga momwe kachirombo ka HIV kamene kamayambitsa kutetezeka kwa chitetezo cha mthupi mwa kupha CD4 T-cells "wothandizira" mwakhama.
Komanso, mphamvu ya thupi yolimbana ndi kachilombo ka HIV ndi yotchedwa "wakupha" CD8 T-cells imawongolera pang'onopang'ono pamene thupi likumana ndikutaya thupi . Pa matenda aakulu, chitetezo cha mthupi chidzasintha nthawi zonse kuti zisawonongeke (kuyambitsa matenda a autoimmune) kapena kutsimikiziridwa (kulola tizilombo toyambitsa matenda kufalikira).
Makamaka pa nthawi yayitali matendawa, kachilombo ka HIV kamangokhala ngati maselo a CD4 akufafanizidwa pang'onopang'ono ndipo thupi silingakwanitse kuzindikira tizilombo toyambitsa matenda (zofanana ndi za odwala khansa). Izi zikachitika, chitetezo cha mthupi mosadziwika "chimayika mabaki" pamayankhidwe oyenera, kupangitsa kuti azidziletsa okha.
Asayansi ku yunivesite ya Emory ayamba kufufuza za kugwiritsa ntchito ma antibodies omwe amatchedwa liplimumab , omwe angathe "kumasula mabaki" ndikuwongolera ma CD8 T-selo.
Chimodzi mwa zinthu zowonjezera zomwe analandira, zomwe zikuchitika mu mayesero a primate, zimagwiritsa ntchito odwala olumala "chigoba" cha kachilombo koyambitsa matenda a herpes kamene imatchedwa "CMV" yomwe imaphatikizidwa zidutswa zopanda matenda (SIV) (primate version of HIV) . Pamene maphunziro ali opangidwa ndi ma CMV, thupi limayankha ku "matenda" omwe amachititsa kachilombo ka CD8 T kuti athetse zomwe amakhulupirira kuti ndi SIV.
Chomwe chimapangitsa mtundu wa CMV kukhala wopondereza makamaka ndi chakuti kachilombo ka herpes sikanachotsedwe ku thupi, ngati tizilombo toyambitsa matenda, koma timapitiriza kuyankha mobwerezabwereza. Kaya izi zikuteteza chitetezo cha mthupi kwa nthawi yayitali sichiyenera kutsimikiziridwa, koma chimapereka chitsimikiziro chotsimikizira.
Kuyeretsa ndi Kupha Kachilombo ka HIV
Chimodzi mwa zopinga zazikulu zowonjezera katemera wa kachilombo ka HIV ndilo liwiro lomwe kachilombo ka HIV kamatha kukhazikitsa zida zowonongeka kuti zisawononge chitetezo cha mthupi. Amakhulupirira kuti izi zingachitike mofulumira ngati maola anayi pokhapokha ngati akugonana ndi abambo- kuthamanga msanga kuchokera ku tsamba la kachilombo koyambitsa matendawa mpaka masiku anai muzochitika zina zogonana kapena zosagonana .
Mpaka pano, sitidziwa konse ngakhale kuti malowa ndi aakulu kapena akuluakulu omwe angakhale ndi mphamvu zowononga tizilombo toyambitsa matenda (ie, kubwerera kwa kachirombo ka HIV).
Kafukufuku wina woopsa kwambiri lero akuphatikizapo njira yomwe imatchedwa "kupha" pogwiritsira ntchito othandizira omwe angathe "kukankhira" HIV yowonongeka mwatulukamo, motero kulola wachiwiri kapena njira kuti "aphe" kachilombo kameneka kumeneku.
Pankhaniyi, asayansi akhala akugwiritsa ntchito mankhwala osokoneza bongo omwe amatchedwa HDAC, omwe akhala akugwiritsidwa ntchito pochiza matenda a khunyu ndi matenda a maganizo. Ngakhale kuti kafukufuku wasonyeza kuti mankhwala atsopano a HDAC angathe "kudzutsa" matenda oopsa kwambiri, palibe amene amatha kuthetsa zitsimezo kapena kuchepetsa kukula kwake. Zikhulupiriro zikugwiritsidwa ntchito palimodzi pogwiritsa ntchito HDAC ndi othandizira ena amodzi (kuphatikizapo PEP005 , omwe amagwiritsidwa ntchito pochita khansa ya khungu la khungu).
Komabe, vuto lalikulu ndilokuti HDAC zowonongeka zingayambitse poizoni komanso kuthetsa chitetezo cha mthupi. Chotsatira chake, asayansi akuyang'ananso pa gulu la mankhwala, otchedwa TLA agonists, omwe amawoneka kuti akhoza kulimbikitsa chitetezo cha mthupi osati "kutsitsa" kachilombo kobisika. Maphunziro oyambirira a nyamakazi akhala akulonjeza, osati kuchepetsa kuyesedwa koyerekeza kwa malo osungirako osakanikirana koma kuwonjezeka kwakukulu kwa CD8 "killer" cell activation.
> Zotsatira:
> Rubens, M ;; Ramamoorthy, V .; Saxena, A .; et al. "Katemera wa kachilombo ka HIV: Zotsatira zaposachedwapa, Njira zowonongeka, ndi Malangizo amtsogolo." Journal of Research Immunology. April 25, 2015; Vol. 2015; lembani: 10.1155 / 2015/560347.
> Markowitz, M. "Mphunzitsi wa HIV Elite Controller Study (MMA-0951)." Yunivesite ya Rockefeller; New York, NY; February 9, 2011.
> Schoofs, T .; Klein, F .; Braunschweig, M .; et al. "Mankhwala a HIV-1 ndi monoclonal antibody 3BNC117 amachititsa kuti chitetezo cha mthupi chitetezeke ku HIV-1." Sayansi. May 5, 2016; lembani: 10.1126 / science.aaf0972.
> Jones, R .; O'Connor, R .; Mueller, S .; et al. "Histone Deacetylase Inhibitors Imathetsa Kuchotsa Maselo Opatsirana ndi HIV ndi T-Lymphocytes ya Cytotoxic . " Mavitamini a PLoS . August 14, 2014; 10 (8): e1004287 DOI: 10.1371 / magazini.ppat.1004287.
> Moody, M .; Santra, S .; Vandergrift, N .; et al. "7/8 (TLR7 / 8) ndi TLR9 Agonists amagwirizana kuti apange mauthenga a anti-antibody antibody mu Rhesus Macaques." Journal of Virology. March 2014; 88 (6): 3329-3339.