{"id":5584,"date":"2020-05-03T20:46:30","date_gmt":"2020-05-03T17:46:30","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=5584"},"modified":"2020-05-03T20:46:32","modified_gmt":"2020-05-03T17:46:32","slug":"alerjiler-suclusu-kim","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/alerjiler-suclusu-kim\/","title":{"rendered":"ALERJ\u0130LER: SU\u00c7LUSU K\u0130M?"},"content":{"rendered":"\n

\u00c7o\u011fu insan\u0131n sahip oldu\u011fu alerjiler, asl\u0131nda bir\u00e7ok farkl\u0131 etkenden kaynaklanabilen biyolojik tepkilerdir. Alerji belirtileri ki\u015filer aras\u0131nda farkl\u0131l\u0131k g\u00f6sterebildi\u011fi gibi, bir ki\u015finin ba\u011f\u0131\u015f\u0131kl\u0131k sistemi de her zaman ayn\u0131 maddeye ayn\u0131 \u015fekilde kar\u015f\u0131l\u0131k vermeyebilir.\u00a0 Baz\u0131lar\u0131m\u0131z bitkilerden gelen polenlere tepki g\u00f6sterirken; baz\u0131lar\u0131m\u0131z f\u0131st\u0131k, \u00e7ikolata gibi yiyeceklere tepki g\u00f6sterebilir. Peki alerjilerdeki bu ki\u015fisel farkl\u0131l\u0131klar neyden kaynaklanmakta ve v\u00fccutlar\u0131m\u0131z ne zaman bir maddeye alerjik \u015fekilde kar\u015f\u0131l\u0131k vermektedir? Bu farkl\u0131l\u0131klar, ki\u015finin maruz kald\u0131\u011f\u0131 alerjinin tipine (\u00f6rne\u011fin havada u\u00e7u\u015fan polenin t\u00fcr\u00fcne), konsantrasyonuna ve ki\u015finin daha \u00f6nce bu etmenle kar\u015f\u0131la\u015f\u0131p kar\u015f\u0131la\u015fmad\u0131\u011f\u0131na ba\u011fl\u0131 olarak geli\u015febilir.\u00a0<\/p>\n\n\n\n

Alerjilerin Mekanizmas\u0131<\/h3>\n\n\n\n

\u00d6ncelikle, alerjilerin tam olarak ne olduklar\u0131na ve hangi mekanizmalar sayesinde ger\u00e7ekle\u015ftirildiklerine dikkat \u00e7ekmek istiyorum. Alerjiler genelde zarars\u0131z maddelere kar\u015f\u0131 ‘asl\u0131nda gereksiz olan’ ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131tlar\u0131 olarak de\u011ferlendirilirler (1). Ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin bu cevab\u0131, sistemin alerjenleri v\u00fccuda zarar verebilecek madde olarak g\u00f6rmesinden kaynaklanmaktad\u0131r. Polen, toz, yer f\u0131st\u0131\u011f\u0131 alerjik tepki g\u00f6sterilen yayg\u0131n maddeler aras\u0131nda say\u0131labilir. Son y\u0131llarda geli\u015fmi\u015f \u00fclkelerde alerjilerin daha da yayg\u0131nla\u015fmakta oldu\u011fu tespit edilmi\u015ftir (1).  <\/p>\n\n\n\n

\"\"
(https:\/\/www.eufic.org\/tr\/healthy-living\/category\/alerji-ve-hassasiyet<\/a>)<\/figcaption><\/figure>\n\n\n\n

Alerjik cevap, ba\u011f\u0131\u015f\u0131kl\u0131k sistemindeki T h\u00fccrelerinin bir \u00e7e\u015fidinin, yabanc\u0131 bir h\u00fccrenin antijenine temas\u0131 ile ba\u015flar. Bu gruptaki T h\u00fccreleri, IL-4 denen bir sitokin molek\u00fcl\u00fcn\u00fc sentezleyebilmektedir. Lenfositler, antijeni g\u00f6rd\u00fckten sonra antikor \u00fcretimine ba\u015flanmas\u0131 i\u00e7in B h\u00fccreleriyle etkile\u015fim kurarlar. Bu etkile\u015fimin sonucunda B h\u00fccrelerinden IgE denilen bir antikorun \u00fcretimine ba\u015flan\u0131r. Bu antikorun mast ve bazofil h\u00fccrelerine ba\u011flanmas\u0131 sonucunda da ba\u011f\u0131\u015f\u0131kl\u0131k sistemi h\u00fccreleri, hem alerjeni tan\u0131r hem de ona tepki g\u00f6sterebilecek hale gelmi\u015f olurlar (2). IgE antikoru, di\u011fer antikorlardan farkl\u0131 olarak 2 tane a\u011f\u0131r protein zinciri bar\u0131nd\u0131rmakta ve bunun sayesinde de bu antikorlar hedef h\u00fccrelerine ba\u011flanabilmektedir (3). IgE antikorunun varl\u0131\u011f\u0131 ve y\u00f6netti\u011fi mekanizma, 20. y\u00fczy\u0131lda ke\u015ffedilmi\u015ftir. Prausnitz ve Kustner, yapt\u0131klar\u0131 ara\u015ft\u0131rmalar sayesinde bir alerjik tepkiye yol a\u00e7an fakt\u00f6r\u00fcn hassas bir hastan\u0131n serumundan, hassasiyet g\u00f6stermeyen bir hastan\u0131n serumuna aktar\u0131labildi\u011fini g\u00f6zlemlemi\u015flerdir (3). 1960’l\u0131 y\u0131llarda da birbirlerinden ba\u011f\u0131ms\u0131z olarak birka\u00e7 grup ara\u015ft\u0131rmac\u0131, IgE’yi bu fakt\u00f6r olarak tan\u0131mlam\u0131\u015ft\u0131r (3).<\/p>\n\n\n\n

Ba\u011f\u0131\u015f\u0131kl\u0131k mekanizmalar\u0131ndan yola \u00e7\u0131karak, Gell ve ark., alerjik tepkileri 4 farkl\u0131 kategoride incelemi\u015ftir (4). Bu s\u0131n\u0131fland\u0131rma, zaman i\u00e7inde de\u011fi\u015fikli\u011fe u\u011fram\u0131\u015f olsa da, bizlere alerjiler ve hipersensitivite tepkileri hakk\u0131nda bir f\u0131ikir verebilir:<\/p>\n\n\n\n

Tip 1: IgE antikoruyla birle\u015fen mast h\u00fccrelerinin y\u00f6netti\u011fi, saniyeler i\u00e7inde histamin gibi etken maddelerin salg\u0131lanmas\u0131n\u0131 sa\u011flayan t\u00fcrd\u00fcr. Bu kategoride ast\u0131m bron\u015fit, yemek veya baz\u0131 ila\u00e7 alerjileri ve sistemik anafilaksi gibi durumlar bulunur.<\/p>\n\n\n\n

Tip 2: IgE antikorunun h\u00fccresel antijene ba\u011flanmas\u0131n\u0131 i\u00e7erir. Bu etkile\u015fim, antijene sahip olan h\u00fccrenin yok edilmesiyle son bulur. <\/p>\n\n\n\n

Tip 3: Serbest dola\u015fan antikorlar\u0131n ve baz\u0131 antijenlerin bir araya gelerek olu\u015fturdu\u011fu kompleks sayesinde olu\u015fturulan alerjik tepkidir. Histamin ve anafilatoksin salg\u0131lanmas\u0131  ile ger\u00e7ekle\u015fir.<\/p>\n\n\n\n

Tip 4: Semptomlar, alerjenle temastan 12-48 saat sonra ger\u00e7ekle\u015fir.<\/p>\n\n\n\n

Bu tip reaksiyonlara ek olarak, yak\u0131n zamanda farkl\u0131 alerjik tepki \u00e7e\u015fitleri de \u00f6nerilmi\u015f ve kabul edilmi\u015ftir (3).  <\/p>\n\n\n\n

\"\"
(Immunoglobulin yap\u0131s\u0131n\u0131 g\u00f6steren bir resim. K\u00fc\u00e7\u00fck zincir, antijen, b\u00fcy\u00fck zincir ve antijen ba\u011flanma noktas\u0131 temsil edilmi\u015f. https:\/\/www.vectorstock.com\/royalty-free-vector\/structure-of-the-antibody-molecule-ige-and-vector-21211554<\/a>)<\/figcaption><\/figure>\n\n\n\n

Alerjiler Neden Var?<\/h3>\n\n\n\n

Alerjik tepkilerin mekanizmalar\u0131n\u0131 g\u00f6rd\u00fck, ama bu tepkinin olu\u015fmas\u0131n\u0131n alt\u0131nda yatan neden nedir? D\u00fcnya’da milyonlarca insan g\u00fcnl\u00fck hayat\u0131nda, \u00f6zellikle de bahar aylar\u0131nda, s\u0131k s\u0131k kar\u015f\u0131la\u015ft\u0131klar\u0131 polenler gibi maddelerle temas kurduklar\u0131nda nefes darl\u0131\u011f\u0131, ciltte ka\u015f\u0131nt\u0131, hap\u015f\u0131rma gibi bir\u00e7ok bi\u00e7imde tepki verebiliyorlar. Alerjilerin bu kadar yayg\u0131n olmalar\u0131na ve uzun zamand\u0131r bilinmelerine ra\u011fmen bilim insanlar\u0131, hala neden olu\u015ftuklar\u0131n\u0131 tam olarak bilmiyorlar (5). Ancak bu konu \u00fczerinde \u00e7al\u0131\u015fan bilim insanlar\u0131 aras\u0131ndaki en yayg\u0131n d\u00fc\u015f\u00fcnce, alerjilerin sadece yanl\u0131\u015f y\u00f6nlendirilmi\u015f birer imm\u00fcn yan\u0131t oldu\u011fu y\u00f6n\u00fcnde.  Yak\u0131n zamanda bu d\u00fc\u015f\u00fcnceden farkl\u0131 y\u00f6nde sonu\u00e7lar veren Stanford ve Yale \u00dcniversitesinde y\u00fcr\u00fct\u00fclen ara\u015ft\u0131rmalar (6), farelerin bir \u00e7e\u015fit zehirle eser miktarda temas kurmalar\u0131n\u0131n v\u00fccutta antikor \u00fcretimini ve zehirle ilerde kar\u015f\u0131la\u015fma olas\u0131l\u0131\u011f\u0131na kar\u015f\u0131n korunmay\u0131 art\u0131rd\u0131\u011f\u0131n\u0131 ortaya koymu\u015ftur. Bu \u015fekilde v\u00fccudun zehirlere kar\u015f\u0131 haz\u0131rl\u0131k yapabilmesi ve 3 hafta sonra uygulanan \u00f6l\u00fcmc\u00fcl olabilecek dozdaki zararl\u0131 maddeye kar\u015f\u0131 b\u00fcy\u00fck oranda koruma sa\u011flanm\u0131\u015ft\u0131r. Kaydedilen verilere g\u00f6re, ilk ba\u015fta az miktarda zehire kar\u015f\u0131 antikor \u00fcretebilen farelerin hayatta kalma oranlar\u0131 \u00e7ok daha y\u00fcksek \u00e7\u0131km\u0131\u015ft\u0131r. Zehirli maddelere kar\u015f\u0131, benzer bi\u00e7imlerde verilen ba\u011f\u0131\u015f\u0131kl\u0131k cevaplar\u0131n\u0131n, ba\u015fka alerjenlere verilen tepkilerin alt\u0131nda yatan mekanizmalar\u0131 ve nedenlerini de ayd\u0131nlatabilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir (5). Ancak hala, anafilaksi gibi ki\u015finin hayat\u0131n\u0131 tehdit edebilen durumlar\u0131n neden tepki mekanizmalar\u0131m\u0131z aras\u0131nda yer ald\u0131\u011f\u0131 sorusu tam olarak cevaplanamam\u0131\u015ft\u0131r. Anafilaksi tepkisini, b\u00f6cek \u0131s\u0131r\u0131klar\u0131 ve yiyecek alerjenler gibi bir\u00e7ok durum tetikleyebilmektedir (7).  <\/p>\n\n\n\n

\"\"
(Anafilaksiye neden olan en yayg\u0131n etmenlerin \u00f6zetlendi\u011fi bir resim. https:\/\/onlinefirstaid.com\/food-allergies-and-anaphylaxis\/<\/a>)<\/figcaption><\/figure>\n\n\n\n

Alerjilerin Geneti\u011fi<\/h3>\n\n\n\n

Bilim insanlar\u0131, alerjiler ne kadar kompleks fenotiplerde kendilerini g\u00f6steren hastal\u0131klar olsalar da, genetik bir temelleri oldu\u011fu konusunda hemfikirler (8). Aile a\u011fac\u0131 ve alerjik hastal\u0131klar\u0131n s\u0131kl\u0131\u011f\u0131 aras\u0131ndaki ili\u015fkilerin ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar; birinci derece aile yak\u0131nlar\u0131nda alerjik hastal\u0131k g\u00f6r\u00fcld\u00fc\u011f\u00fc takdirde bireyin alerji riskinde belirgin bir art\u0131\u015f oldu\u011funu belirtmi\u015ftir (9). Bu art\u0131\u015f, ailesinde alerji g\u00f6r\u00fclmeyen bir bireyin 3 kat\u0131 olarak de\u011ferlendirilmi\u015ftir (8). Dolay\u0131s\u0131yla, ailede pozitif vakalar\u0131n bulunmas\u0131, alerjik hastal\u0131k yayg\u0131nl\u0131\u011f\u0131n\u0131 ve ilerleyi\u015fini anlayabilmek i\u00e7in en \u00f6nemli ara\u00e7lardan biri olmu\u015ftur. Literat\u00fcrde, alerjilerin y\u00fcksek oranda kal\u0131tsal oldu\u011funa dair bir\u00e7ok bulgu yer almaktad\u0131r. Daha g\u00fcncel \u00e7al\u0131\u015fmalarda da genom boyu ili\u015fkilendirme \u00e7al\u0131\u015fmalar\u0131 (genome-wide association studies, GWAS) s\u0131k\u00e7a kullan\u0131lm\u0131\u015f ve bir\u00e7ok yeni bilginin literat\u00fcre ge\u00e7mesine arac\u0131 olmu\u015ftur. \u00c7al\u0131\u015fmalar, hem alerjilerin alt\u0131nda yatan genetik yap\u0131lar hakk\u0131nda fikir olu\u015fturabilmemizi sa\u011flam\u0131\u015f, hem de ki\u015finin i\u00e7inde b\u00fcy\u00fcd\u00fc\u011f\u00fc ve ya\u015famakta oldu\u011fu ortamlar\u0131n da alerjilerine etkisini daha iyi anlamam\u0131z i\u00e7in \u00f6nc\u00fc olabilmi\u015ftir.\u00a0<\/p>\n\n\n\n

\"\"
(Alerji testi. https:\/\/bgdo.alexeevphoto.ru\/skin-allergies\/7392-allergy.php<\/a>)

<\/figcaption><\/figure>\n\n\n\n

Yine GWAS modellemelerine dayanarak y\u00fcr\u00fct\u00fclen alerjik ast\u0131m hakk\u0131ndaki b\u00fcy\u00fck \u00e7apl\u0131 GABRIEL projesi ve ilerdeki zamanlarda y\u00fcr\u00fct\u00fclen buna benzer ba\u015fka \u00e7al\u0131\u015fmalarda; ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131tlar\u0131n\u0131 uyaran IL33 ve ST2 gibi lokuslar\u0131n alerjik ast\u0131m\u0131 olan hastalarda belirli mutasyonlara u\u011frad\u0131\u011f\u0131 ve hastal\u0131k ilerleyi\u015finde belirleyici rol oynad\u0131klar\u0131 kaydedilmi\u015ftir (8). IL-33, Th2 ba\u011f\u0131\u015f\u0131kl\u0131k cevab\u0131n\u0131 uyarmaktad\u0131r ve bu \u015fekilde de alerjik tepkiyi y\u00f6nlendirdi\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir (10). Dolay\u0131s\u0131yla genel olarak alerjilerin genetik temelinde; Th2 h\u00fccrelerinin aktivitesini, T h\u00fccresi farkl\u0131la\u015fmas\u0131n\u0131, cilt ve mukoza tabakalar\u0131n\u0131n fonksiyonlar\u0131n\u0131 etkileyen genlerin ve lokuslar\u0131n bulundu\u011fu d\u00fc\u015f\u00fcn\u00fclmektedir (11). Buna ek olarak ilgin\u00e7 bir \u00f6rnek, kedi alerjisi ile insan l\u00f6kosit antijenini kodlayan gen aras\u0131ndaki do\u011frusal ba\u011flant\u0131d\u0131r (12). Ancak hala alerjinin genetik temelleri ve patojenin mekanizmalar\u0131 hakk\u0131nda ara\u015ft\u0131r\u0131lmas\u0131 ve anla\u015f\u0131lmas\u0131 gereken bir\u00e7ok \u015fey bulunmaktad\u0131r.\u00a0<\/p>\n\n\n\n

Alerjilerin art\u0131\u015f\u0131nda etkili oldu\u011fu ortaya at\u0131lm\u0131\u015f bir di\u011fer teori de ‘hijyen hipotezi’dir (13). Bu teori, genel olarak epidemiyolojik ara\u015ft\u0131rmalara dayanmakta ve bat\u0131 \u00fclkelerindeki a\u015f\u0131lar\u0131n yayg\u0131nla\u015ft\u0131r\u0131lmas\u0131yla enfeksiyon hastal\u0131klar\u0131n s\u0131kl\u0131\u011f\u0131n\u0131n olduk\u00e7a azalmas\u0131n\u0131 otoimm\u00fcn ve alerjik hastal\u0131klar\u0131n art\u0131\u015f\u0131n\u0131 dile getirmektedir (13). 1989 y\u0131l\u0131nda Strachan taraf\u0131ndan \u00f6ne s\u00fcr\u00fclen bu teori, ilk olarak bahar nezlesi s\u0131kl\u0131\u011f\u0131n\u0131n incelenmesiyle ortaya \u00e7\u0131km\u0131\u015ft\u0131r. Strachan, kendinden daha b\u00fcy\u00fck karde\u015fleri olan \u00e7ocuklarda bahar nezlesinin daha nadir g\u00f6r\u00fcld\u00fc\u011f\u00fcn\u00fc kaydetmi\u015f (14), bu istatisti\u011fi de bu \u00e7ocuklar\u0131n karde\u015flerinden dolay\u0131 daha az hijyenik ortamlarda bulunma durumunda olduklar\u0131na yormu\u015ftur (15). Buna dayanarak da erken hayatlar\u0131nda \u00e7e\u015fitli mikroplarla temasta bulunan \u00e7ocuklar\u0131n, ilerleyen zamanlarda ba\u011f\u0131\u015f\u0131kl\u0131k sistemlerinde daha az hipersensitivite durumlar\u0131na sahip olacaklar\u0131n\u0131 d\u00fc\u015f\u00fcnm\u00fc\u015ft\u00fcr. Strachan\u2019\u0131n bu g\u00f6zlemlerinden sonra birka\u00e7 ara\u015ft\u0131rma da laboratuvarda, antikor \u00fcretimini takip ederek benzer sonu\u00e7lar\u0131 desteklemi\u015ftir (15). Ancak yak\u0131n zamanda, hijyen hipotezi ve onu destekleyen d\u00fc\u015f\u00fcnceler belli de\u011fi\u015fimlere u\u011fram\u0131\u015f, bu hipotezi hem destekleyen hem de reddeden ara\u015ft\u0131rmalar y\u00fcr\u00fct\u00fclm\u00fc\u015ft\u00fcr. Bilim insanlar\u0131 bu s\u00fcre\u00e7 boyunca alerjilerde rol oynayan mikroflora gibi sistemlerin \u00f6nemini de ara\u015ft\u0131rmaya ba\u015flam\u0131\u015ft\u0131r. <\/p>\n\n\n\n

2012 y\u0131l\u0131nda D\u00fcnya\u2019daki yeti\u015fkinlerin %7,5\u2019inin bahar alerjisiyle ba\u015f etti\u011fi tespit edilmi\u015ftir (16). Benzer alerjilerin s\u0131kl\u0131klar\u0131n\u0131n da artmakta oldu\u011fu \u00e7e\u015fitli ara\u015ft\u0131rmalarla kaydedilmi\u015ftir. Alerjiler de g\u00fcn\u00fcm\u00fczde yayg\u0131n olan bir\u00e7ok hastal\u0131k gibi kompleks sa\u011fl\u0131k durumlar\u0131d\u0131r. Yani olu\u015fmalar\u0131nda ve d\u0131\u015favurumlar\u0131nda biyolojik ve \u00e7evresel bir\u00e7ok fakt\u00f6r etkilidir. Dolay\u0131s\u0131yla genetik temellerini tespit etmek ve kesinle\u015ftirmek kar\u0131\u015f\u0131k bir s\u00fcre\u00e7tir. Bu konuda sahip oldu\u011fumuz bilgi birikimini geni\u015fletmek i\u00e7in ara\u015ft\u0131rmalar hala devam etmekte ve her g\u00fcn alerjilerin mekanizmas\u0131 hakk\u0131nda bilinenler artmaktad\u0131r.\u00a0
<\/p>\n\n\n\n

Kaynaklar<\/strong><\/h3>\n\n\n\n

(1) British Society for Immunology, Allergy.  https:\/\/www.immunology.org\/policy-and-public-affairs\/briefings-and-position-statements\/allergy<\/a><\/p>\n\n\n\n

(2)  Janeway, C. ve ark. (2001) Immunobiology: Fifth Edition. New York and London: Garland Science. <\/p>\n\n\n\n

(3) Saha G.K. (2016) <\/em>Mechanism of Allergic Reaction. Dust Allergy: Cause & Concern.<\/em> Springer, Singapore.<\/p>\n\n\n\n

(4) Gell, P.G.H. and Coombs, R.R.A. (1963) The classification of allergic reactions underlying disease. Clinical Aspects of Immunology<\/em> (Coombs, R.R.A. and Gell, P.G.H., eds) Blackwell Science.\u00a0<\/p>\n\n\n\n

(5) Maron, D. F. (2013) ‘Dear Evolution, Thanks for the Allergies’. Scientific American<\/em>. https:\/\/www.scientificamerican.com\/article\/dear-evolution-thanks-for\/<\/a><\/p>\n\n\n\n

(6) Palm, N. ve ark. (2013) Bee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity. Immunity:<\/em> Volume 39, Issue 5<\/a>, 14 November 2013, Pages 976-985.<\/p>\n\n\n\n

(7) https:\/\/www.webmd.com\/assetid-091e9c5e80008fc2<\/a><\/p>\n\n\n\n

(8) Ortiz, R., Barnes, K. (2015) Genetics of Allergic Diseases. Immunol Allergy Clin North Am<\/em>. 35(1): 19\u201344. doi:10.1016\/j.iac.2014.09.014.<\/p>\n\n\n\n

(9) Melen E. ve ark. Genome-wide association study of body mass index in 23 000 individuals with and without asthma. Clin Exp Allergy.<\/em> 2013; 43:463\u2013474.<\/p>\n\n\n\n

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<\/p>\n\n\n\n


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