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Ukuqhubela phambili kwiNkcazo yoMbulali weNdalo (NK) kwiiseli ezingaphezu kweminyaka eyi-50

2024-07-18

Ukusukela kwiingxelo zokuqala ze-lymphocytes ezibonisa ukubulawa "okungangqalanga" kweeseli zethumba ngo-1973, ukuqonda kunye nokubaluleka kweeseli ze-Natural Killer (NK) ziye zavela kakhulu. Ngo-1975, uRolf Kiessling kunye noogxa kwiKarolinska Institute baqulunqa igama elithi "Natural Killer" iiseli, beqaqambisa isakhono sabo esikhethekileyo sokuhlasela ngokuzenzekelayo iiseli zethumba ngaphandle kokuvuselela kwangaphambili.

Kule minyaka ingamashumi amahlanu ilandelayo, iilabhoratri ezininzi kwihlabathi jikelele ziye zafunda ngokubanzi iiseli ze-NK kwi-vitro ukucacisa indima yazo kukhuselo lomkhosi kumathumba kunye neentsholongwane zentsholongwane, kunye nemisebenzi yazo yolawulo ngaphakathi kukhuselo lomzimba.

 

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Iiseli ze-NK: I-Pioneering Innate Lymphocytes

Iiseli ze-NK, amalungu okuqala abonakaliswe kwintsapho ye-lymphocyte yokuzalwa, akhusela amathumba kunye ne-pathogens ngokusebenzisa umsebenzi othe ngqo we-cytotoxic kunye ne-secretion ye-cytokines kunye ne-chemokines. Ekuqaleni ibibizwa ngokuba yi "null cells" ngenxa yokungabikho kweziphawuli, ukuqhubela phambili kulandelelwano lweseli enye ye-RNA, i-flow cytometry, kunye ne-mass spectrometry ivumele ulwahlulo oluneenkcukacha lwe-NK cell subtypes.

Iminyaka elishumi yokuQala (1973-1982): Ukufumanisa i-Cytotoxicity engacacanga

Ngasekupheleni kwee-1960 kunye no-1970s zakuqala zabona uphuhliso lweemvavanyo ezilula ze-vitro ukulinganisa i-cytotoxicity yeseli. Ngo-1974, u-Herberman kunye noogxa babonisa ukuba i-lymphocyte yegazi ejikelezayo evela kubantu abaphilileyo inokubulala iiseli ezahlukeneyo ze-lymphoma. U-Kiessling, uKlein, kunye no-Wigzell bachaza ngakumbi i-lysis ezenzekelayo yeeseli ze-tumor ngama-lymphocytes avela kwiigundane ezingenayo i-tumor, ebiza lo msebenzi "ukubulala kwendalo."

Ishumi lesibini leminyaka (1983-1992): Ukubonakaliswa kwePhenotypic kunye noKhuseleko lweNtsholongwane

Ngexesha le-1980, ugxininiso lwatshintshela kwi-phenotypic characterization yeeseli ze-NK, ezikhokelela ekuchongweni kwee-subpopulations kunye nemisebenzi eyahlukileyo. Ngo-1983, izazinzulu ziye zachonga iiseti ezisebenzayo ezahlukeneyo zeeseli ze-NK zabantu. Uphononongo olongezelelweyo lubonise indima ebalulekileyo kwiiseli ze-NK ekukhuseleni i-herpesviruses, ibonakaliswe sisigulana esinosulelo olunzima lwe-herpesvirus ngenxa yokungabikho kweseli ye-NK yemfuza.

Ishumi lesithathu leminyaka (1993-2002): Ukuqonda i-Receptors kunye neLigands

Inkqubela phambili ebalulekileyo kwiminyaka ye-1990 kunye ne-2000 yokuqala yakhokelela ekuchongeni kunye ne-cloning ye-NK cell receptors kunye ne-ligands yazo. Izinto ezifunyenweyo ezifana ne-NKG2D receptor kunye ne-ligands ezibangelwa uxinzelelo ziseke isiseko sokuqonda iiseli ze-NK '"ezitshintshileyo-self" iindlela zokuqaphela.

Ishumi leSine leminyaka (2003-2012): NK iMemori yeSeli kunye neLayisenisi

Ngokuchasene neembono zemveli, izifundo kwi-2000s zibonise ukuba iiseli ze-NK zinokubonisa iimpendulo ezifana nememori. Abaphandi babonise ukuba iiseli ze-NK zinokulamla iimpendulo ezikhethekileyo ze-antigen kwaye ziphuhlise uhlobo "lwememori" olufana neeseli zokuzikhusela. Ukongezelela, ingcamango ye-NK cell "ilayisensi" yavela, ichaza indlela ukusebenzisana kunye ne-self-MHC molekyuli kunokuphucula ukuphendula kweeseli ze-NK.

Ishumi lesihlanu leminyaka (i-2013-Yangoku): Izicelo zeklinikhi kunye neentlobo ezahlukeneyo

Kwiminyaka elishumi edlulileyo, ukuqhubela phambili kwezobuchwepheshe kuqhube uphando lweseli ye-NK. I-mass cytometry kunye nokulandelelana kwe-RNA yeseli enye ibonakalise ulwahlulo olubanzi lwe-phenotypic phakathi kweeseli ze-NK. Ngokweklinikhi, iiseli ze-NK zibonise isithembiso ekuphatheni i-hematological malignancies, njengoko kuboniswe ngokusetyenziswa ngempumelelo kweeseli ze-CD19 CAR-NK kwizigulane ze-lymphoma ngo-2020.

Amathemba exesha elizayo: Imibuzo engaphendulwanga kunye neeNdawo eziNtsha

Njengoko uphando luqhubeka, kusekho imibuzo emininzi ebangela umdla. Iiseli ze-NK ziyifumana njani inkumbulo ethe ngqo ye-antigen? Ngaba iiseli ze-NK zinokufakwa ukulawula izifo ezizimelayo? Sinokuyoyisa njani imingeni ebangelwa yi-tumor microenvironment ukuze isebenze iiseli ze-NK ngokufanelekileyo? Iminyaka engamashumi amahlanu ezayo ithembisa ukufunyaniswa okuvuyisayo kunye nokungalindelekanga kwi-NK cell biology, enikezela ngezicwangciso ezintsha zonyango lomhlaza kunye nezifo ezosulelayo.