Karolinska Enstit\u00fcs\u00fc Nobel Kurulu; 2011 Fizyoloji veya T\u0131p alan\u0131ndaki Nobel \u00f6d\u00fcl\u00fcn\u00fc, do\u011fu\u015ftan gelen (innate) ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n aktivasyonu alan\u0131ndaki ke\u015fifleriyle Bruce A. Beutler ve Jules A. Hoffmann ve de kazan\u0131lm\u0131\u015f (adaptive) ba\u011f\u0131\u015f\u0131kl\u0131kta dendritik h\u00fccrelerin rol\u00fcn\u00fcn belirlenmesi \u00e7al\u0131\u015fmas\u0131yla Ralph M. Steinman\u2019a verdi. Bu y\u0131l\u0131n Nobel \u00d6d\u00fcl\u00fc sahipleri ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin aktivasyonunda \u00f6nemli prensipleri \u00e7\u00f6zerek bu sistemin anla\u015f\u0131lmas\u0131nda k\u00f6kl\u00fc de\u011fi\u015fiklik yapt\u0131lar.<\/p>\n
Bilim insanlar\u0131 uzun s\u00fcredir bakteri ve di\u011fer organizmalara kar\u015f\u0131 savunmay\u0131 sa\u011flayan ba\u011f\u0131\u015f\u0131kl\u0131k tepkisinin ilk nas\u0131l ba\u015flad\u0131\u011f\u0131n\u0131 ara\u015ft\u0131r\u0131yorlard\u0131. Bruce Beutler ve Jules Hoffmann baz\u0131 mikroorganizmalar\u0131 tan\u0131yabilen ve v\u00fccudun ba\u011f\u0131\u015f\u0131kl\u0131k tepkisinin ilk basama\u011f\u0131 olan do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 aktive eden resept\u00f6r proteini ke\u015ffettiler. Ralph Steinman ise mikroorganizmalar\u0131n v\u00fccuttan temizlenmesi s\u0131ras\u0131nda olu\u015fan kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n aktive edilmesinde ve d\u00fczenlenmesinde dendritik h\u00fccrelerin rol\u00fcn\u00fc ortaya koydu. Bu \u00fc\u00e7 Nobel sahibi; ba\u011f\u0131\u015f\u0131kl\u0131k cevab\u0131n\u0131n, do\u011fu\u015ftan gelen ve kazan\u0131lm\u0131\u015f a\u015famalar\u0131nda nas\u0131l aktive edildi\u011fini belirlediler ve b\u00f6ylece hastal\u0131k mekanizmalar\u0131na yeni bir anlay\u0131\u015f kazand\u0131rd\u0131lar. Bu \u00e7al\u0131\u015fmalar hastal\u0131klardan korunmada; enfeksiyon, kanser ve iltihapl\u0131 hastal\u0131klara kar\u015f\u0131 tedavide farkl\u0131 bak\u0131\u015f a\u00e7\u0131lar\u0131 yaratt\u0131.<\/p>\n
Ba\u011f\u0131\u015f\u0131kl\u0131k sisteminde iki farkl\u0131 savunma mevcuttur. Tehlikeli bir d\u00fcnyada ya\u015famaktay\u0131z ve patojenik mikroorganizmalar (bakteriler, vir\u00fcsler, mantarlar ve parazitler) bizi s\u00fcrekli tehdit etmektedir. Ancak biz \u00e7ok g\u00fc\u00e7l\u00fc bir savunma mekanizmas\u0131na sahibiz. Savunman\u0131n ilk a\u015famas\u0131 olan do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131k, h\u00fccum eden mikroorganizmay\u0131 yok edebilir ve bu sald\u0131r\u0131y\u0131 yok edecek iltihap olu\u015fumunu tetikleyebilir. E\u011fer mikroorganizma bu savunma sistemini ge\u00e7erse, kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131k harekete ge\u00e7er. T ve B h\u00fccreleriyle antikor \u00fcretir ve enfekte olmu\u015f h\u00fccreyi yok eder. Enfeksiyona kar\u015f\u0131 ba\u015far\u0131l\u0131 bir m\u00fccadeleden sonra kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131k sistemi, ayn\u0131 mikroorganizma ile daha sonra tekrar kar\u015f\u0131la\u015f\u0131ld\u0131\u011f\u0131nda daha h\u0131zl\u0131 ve daha g\u00fc\u00e7l\u00fc savunma yapabilsin diye imm\u00fcnolojik haf\u0131za olu\u015fturur. Ba\u011f\u0131\u015f\u0131kl\u0131k sistemindeki bu iki savunma mekanizmas\u0131 enfeksiyonlara kar\u015f\u0131 \u00e7ok iyi koruma sa\u011flar. Ama bu da bir risk te\u015fkil eder. Aktivasyonun e\u015fik de\u011feri \u00e7ok d\u00fc\u015f\u00fck ise ya da endojen (v\u00fccut i\u00e7i) molek\u00fcller bu sistemi aktive edebiliyorsa, iltihapl\u0131 hastal\u0131klar ortaya \u00e7\u0131kabilir.<\/p>\n
Ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin elemanlar\u0131 20. y\u00fczy\u0131l boyunca a\u015fama a\u015fama tan\u0131mland\u0131lar. \u00d6rne\u011fin antikorlar\u0131n nas\u0131l \u00fcretildi\u011fini ve T h\u00fccrelerinin yabanc\u0131 yap\u0131y\u0131 nas\u0131l tan\u0131d\u0131\u011f\u0131n\u0131 biliyorduk. Ancak Beutler, Hoffmann ve Steinman\u2019\u0131n \u00e7al\u0131\u015fmalar\u0131na kadar do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n aktivasyonunu tetikleyici mekanizma ve do\u011fu\u015ftan gelen ile kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131k aras\u0131ndaki ileti\u015fimin arac\u0131 mekanizmas\u0131 gizemini koruyordu.<\/p>\n
Do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131k sens\u00f6r\u00fcn\u00fcn ke\u015ffi Kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 kontrol eden yeni h\u00fccre tipi Temel ara\u015ft\u0131rmalardan t\u0131bbi kullan\u0131ma Karolinska Enstit\u00fcs\u00fc Nobel Kurulu; 2011 Fizyoloji veya T\u0131p alan\u0131ndaki Nobel \u00f6d\u00fcl\u00fcn\u00fc, do\u011fu\u015ftan gelen (innate) ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n aktivasyonu alan\u0131ndaki ke\u015fifleriyle Bruce A. Beutler ve Jules A. Hoffmann ve de kazan\u0131lm\u0131\u015f (adaptive) ba\u011f\u0131\u015f\u0131kl\u0131kta dendritik h\u00fccrelerin rol\u00fcn\u00fcn belirlenmesi \u00e7al\u0131\u015fmas\u0131yla Ralph M. Steinman\u2019a verdi. Bu y\u0131l\u0131n Nobel \u00d6d\u00fcl\u00fc sahipleri ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin aktivasyonunda \u00f6nemli prensipleri \u00e7\u00f6zerek bu sistemin anla\u015f\u0131lmas\u0131nda k\u00f6kl\u00fc de\u011fi\u015fiklik […]<\/p>\n","protected":false},"author":755,"featured_media":44177,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[130,38,4696],"tags":[6672,6673,6674,629,6675,6671],"class_list":["post-44176","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-93-sayi","category-dergi-sayilari","category-tip","tag-6672","tag-bruce-a-beutler","tag-jules-a-hoffmann","tag-nobel","tag-ralph-m-steinman","tag-tip-odulleri"],"acf":[],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t
\n<\/em><\/strong>Jules Hoffmann ilk \u00f6nc\u00fc bulu\u015funu 1996 y\u0131l\u0131nda \u00e7al\u0131\u015fma arkada\u015f\u0131yla birlikte yapm\u0131\u015f oldu\u011fu meyve sineklerinin enfeksiyonla nas\u0131l m\u00fccadele ettikleri hakk\u0131ndaki ara\u015ft\u0131rmas\u0131yla ortaya koymu\u015ftur. Sineklerle olan \u00e7al\u0131\u015fmalar\u0131, Toll genini de i\u00e7eren birka\u00e7 farkl\u0131 gende mutasyonlar meydana getirerek ba\u015flam\u0131\u015ft\u0131r. (Christiane N\u00fcsslein-Volhard taraf\u0131ndan ke\u015ffedilmi\u015f olan Toll geninin embriyonal geli\u015fimdeki etkisi bu bilim adam\u0131na 1995 y\u0131l\u0131nda Nobel \u00d6d\u00fcl\u00fc kazand\u0131rm\u0131\u015ftr.) Hoffmann meyve sine\u011fini bir bakteri ya da mantar ile enfekte etti\u011finde, Toll geni mutant olanlar\u0131n \u00f6ld\u00fc\u011f\u00fcn\u00fc tespit etmi\u015ftir. Bunun nedeni bu mutant sineklerin yeterli derecede etkili savunma sahibi olmay\u0131\u015flar\u0131d\u0131r. Bunlardan yola \u00e7\u0131karak bu bilim insan\u0131, Toll geni \u00fcr\u00fcn\u00fcn\u00fcn patojenlerin alg\u0131lanmas\u0131 i\u00e7in gerekli oldu\u011funu ve dolay\u0131s\u0131yla Toll geni aktivasyonunun patojenlere kar\u015f\u0131 g\u00fc\u00e7l\u00fc bir savunma mekanizmas\u0131 olu\u015fumunda \u00f6nemli oldu\u011funu \u00f6ne s\u00fcrm\u00fc\u015ft\u00fcr. Bruce Beutler, lipopolisakkarit (LPS) ad\u0131 verilen ve septik \u015foka (ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin y\u00fcksek derecede tetiklenmesinden kaynakl\u0131 ya\u015fam\u0131 tehdit eden durum) neden olan bakteriyel \u00fcr\u00fcnlere ba\u011flanan resept\u00f6rleri ara\u015ft\u0131rm\u0131\u015ft\u0131r. 1998\u2019de Beutler ve arkada\u015flar\u0131 LPS\u2019lere kar\u015f\u0131 diren\u00e7li bir farenin meyve sine\u011findeki Toll geni ile tamam\u0131yla benzer bir geninde mutasyon saptam\u0131\u015ft\u0131r. Bu Toll benzeri resept\u00f6r\u00fcn\u00fcn (Toll-like receptor-TLR) yakalanmas\u0131 zor olan LPS resept\u00f6r\u00fc oldu\u011fu ortaya \u00e7\u0131km\u0131\u015ft\u0131r. Bu resept\u00f6r LPS\u2019ye ba\u011fland\u0131\u011f\u0131 zaman iltihaba neden olan sinyaller aktive edilir ve LPS dozu a\u015f\u0131r\u0131 oldu\u011funda da septik \u015fok g\u00f6r\u00fcl\u00fcr. Bu bulgular memeli ve meyve sineklerinin bir patojen ile kar\u015f\u0131la\u015ft\u0131klar\u0131nda do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 aktive etmek i\u00e7in ayn\u0131 molek\u00fcl\u00fc kulland\u0131klar\u0131n\u0131 g\u00f6stermi\u015ftir. B\u00f6ylece do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n sens\u00f6r\u00fc ke\u015ffedilmi\u015ftir. Hoffmann ve Beutler\u2019in bu bulu\u015fu do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131k \u00fczerine olan ara\u015ft\u0131rmalar\u0131n a\u015f\u0131r\u0131 art\u0131\u015f\u0131na sebep olmu\u015ftur. \u0130nsan ve farede yakla\u015f\u0131k bir d\u00fczine farkl\u0131 TLR tan\u0131mlam\u0131\u015ft\u0131r. Bunlar\u0131n her biri mikroorganizmalardaki ortak molek\u00fcllerin belli tiplerini tan\u0131maktad\u0131r. Di\u011fer TLR t\u00fcrlerindeki genetik \u00e7e\u015fitlilik kronik iltihapl\u0131 hastal\u0131klar i\u00e7in y\u00fcksek risk olu\u015ftururken, bu resept\u00f6rlerdeki belli mutasyonlara sahip bireyler enfeksiyonlara kar\u015f\u0131 y\u00fcksek risk ta\u015f\u0131rlar.<\/p>\n
\n<\/em><\/strong>1973\u2019te Ralph Steinman \u201cdendritik h\u00fccre\u201d olarak adland\u0131r\u0131lan yeni bir h\u00fccre tipi ke\u015ffetmi\u015ftir. Bu h\u00fccrelerin ba\u011f\u0131\u015f\u0131kl\u0131k sistemi i\u00e7in \u00f6nemli oldu\u011funu \u00f6ne s\u00fcren ara\u015ft\u0131rmac\u0131 dendritik h\u00fccrelerin T h\u00fccrelerini aktive edip etmedi\u011fini ayr\u0131ca kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131kta ve farkl\u0131 maddelere kar\u015f\u0131 olu\u015fturulan imm\u00fcnolojik haf\u0131zan\u0131n geli\u015ftirilmesinde anahtar rol oynay\u0131p oynamad\u0131\u011f\u0131n\u0131 test etmeye devam etmi\u015ftir. H\u00fccre k\u00fclt\u00fcr\u00fc deneylerinde dendritik h\u00fccrelerin varl\u0131\u011f\u0131nda farkl\u0131 maddelere kar\u015f\u0131 T h\u00fccresel cevab\u0131n olu\u015ftu\u011funu g\u00f6stermi\u015ftir. Daha sonra Steinman ve di\u011fer ara\u015ft\u0131rmac\u0131lar, kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n bir yabanc\u0131 madde ile kar\u015f\u0131la\u015ft\u0131\u011f\u0131nda aktive olup olmayaca\u011f\u0131na nas\u0131l karar verdi\u011fi \u00fczerine yo\u011funla\u015fm\u0131\u015flard\u0131r. T h\u00fccresi aktivasyonunun kontrol\u00fc i\u00e7in do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131ktan meydana gelen sinyaller ve dendritik h\u00fccrelerin alg\u0131lamas\u0131 belirlenmi\u015ftir. Bu, v\u00fccudun kendi molek\u00fcllerine kar\u015f\u0131 ata\u011f\u0131n\u0131 engellerken patojenik mikroorganizmalara kar\u015f\u0131 tepki g\u00f6stermesini m\u00fcmk\u00fcn k\u0131lm\u0131\u015ft\u0131r.<\/p>\n
\n<\/em><\/strong>2011 Nobel \u00f6d\u00fcl\u00fc kazand\u0131ran ke\u015fif, ba\u011f\u0131\u015f\u0131kl\u0131k sistemimizin aktivasyonu ve d\u00fczenlenmesiyle ilgili yeni bak\u0131\u015f a\u00e7\u0131s\u0131 kazand\u0131rm\u0131\u015ft\u0131r. Hastal\u0131klar\u0131n \u00f6nlenmesi ve tedavisi i\u00e7in yeni teknikler geli\u015ftirilebilir hale gelmi\u015ftir. Enfeksiyonlara kar\u015f\u0131 a\u015f\u0131lar\u0131n geli\u015ftirilmesi ve t\u00fcm\u00f6rlere kar\u015f\u0131 ba\u011f\u0131\u015f\u0131kl\u0131k sistemini uyaracak giri\u015fimler bunlara \u00f6rnek verilebilir. Ayr\u0131ca bu ke\u015fifler ba\u011f\u0131\u015f\u0131kl\u0131k sistemimizin bizim kendi dokumuza neden sald\u0131rd\u0131\u011f\u0131n\u0131 anlamam\u0131za yard\u0131mc\u0131 olmu\u015ftur. B\u00f6ylece iltihapl\u0131 hastal\u0131klara y\u00f6nelik yeni tedavilere ipu\u00e7lar\u0131 sa\u011flanm\u0131\u015ft\u0131r.<\/p>\n","protected":false},"excerpt":{"rendered":"