Respiracijski alergeni Alergijske reakcije u dišnim putevima D O C. D R. S C. M. T U R K A L J
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1 Respiracijski alergeni Alergijske reakcije u dišnim putevima D O C. D R. S C. M. T U R K A L J D J E Č J A B O L N I C A S R E B R N J A K
2 Općenito o alergijama Alergijske reakcije (ili reakcije preosjetljivosti) izazivaju oštećenja koja mogu biti lokalna, relativno blaga i popravljiva (npr. urtika, rhinoconjuctivitis) ili teža, pa i generalizirana i smrtonosna (npr. generalizirana anafilaksija). Alergijske bolesti specifične su za pojedine bolesnike (od astme do alergija na hranu). Alergijski odgovor usmjeren je prema specifičnim alergijskim proteinima u okolini (alergeni)
3 Antigen Antigen je svaka tvar nepoznata organizmu koja može uzrokovati nastanak imunoreakcije po kemijskoj strukturi najjači antigeni su bjelančevine, iako i polisaharidi te lipidi također mogu imaju imunogenično djelovanje. Antigeni male molekulske mase koje zovemo hapteni, sami ne izazivaju imunoreakcije već se spajaju s nosačima, npr. već stvorenim antitijelima i tako postaju imunogeničnima.
4 Alergijska reakcija - alergija Alergijska reakcija patološka imunološka reakcija na vanjski antigen (alergen) koja dovodi do pojave bolesti Alergija - klinička eksperija alergijskih reakcija posredovanih IgE protutijelima Atopija nasljedna sklonost za razvoj alergijskih reakcija posredovanih IgE protutijelima
5 Atopija- WAO definicija Atopy is a personal and/or familial tendency, usually expressed anytime in life from childhood and adolescence, into maturity, to become sensitized and produce IgE antibodies in response to ordinary exposures to allergens, usually proteins. As a consequence, atopic persons can develop IgEmediated allergic diseases including asthma, rhinoconjunctivitis, or eczema. WAO Nomenclature Review Committee Johansson et al. J Allergy Clin Immunol 2004;113:832-6
6 Revizija klasifikacije reakcija preosjetljivosti (EAACI 2001,2003) Preosjetljivost alergijska nealergijska IgE posredovana Ne-IgE posredovana
7 Alergija Alergijska reakcija Reakciju smatramo alergijskom ako je: 1. poznat antigen (alergen) koji ju je pokrenuo 2. dokazana veza između kontakta s alergenom i pojave oštećenja 3. ustanovimo mehanizam kojim nastaje oštećenje
8 Povijest alergija Prvi opisi: 19. st. opisana preosjetljivost: Koch (tuberkulin), Flexner (serum), von Behring (difterijski toksin) Višekratno injiciranje antigena može izazvati anafilaksiju: Richet i Portier (Actinaria), Arthus (konjski serum davan kunićima), von Pirquet i Schick (serumska bolest) von Pircquet uveo pojam ALERGIJA Faraon Menes
9 Alergen: je antigen, najčešće bjelančevina, koja senzibilizira domaćina, te potiče alergijsku reakciju Čimbenici koji pridonose da antigen postane alergen INTRINZIČKI Kompleksna građa Koncentracija Topljivost Stabilnost Biokemijska aktivnost EKSTRINZIČKI Polutanti Dim cigareta Virusne infekcije Genetska predispozicija i spol Higijena Porođajna težina
10 Koja su obilježja alergena? Još nije jasno kojim mehanizmom i zašto alergeni stimuliraju izlučivanje IL-4
11 Izvor alergena I Izvori alergena: kućna prašina, poleni, spore gljiva, životinje, lijekovi i hrana Aeroalergeni: 1. Poleni: - najčešći alergeni - trave, korov, stabla - uglavnom od biljaka koje se oprašuju vjetrom - veličina polena mikrometara - visoka koncentracija ne samo za vlažnog vremena - proljeće i ljeto, jesen 2. Alergeni iz gljivica:deuteromycotina (Aspergillus, Cladosporium, Penicillinum, Alternaria) i Basidiomycotina (razne vrste gljiva)
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13 Izvori aeroalergena praćenje koncentracije alergena u zraku 13
14 Izvor alergena II Aeroalergeni (nastavak): 3. Alergeni životinjskog podrijetla: - najčešće na mačke i pse - alergeni: prhut, krzno, epitel, ekskreti, slina 4. Alergeni iz artropoda: insekti, grinje (Arahnide) - najvažnije Arahnide su Dermatophagoides pteronysinus, D. Farinae, Euroglyphus maynei - grinje: najčešće u kućnoj prašini: rast im ovisi o mikroklimatskim uvjetima: optimalni 25 C i 80 % vlage - glavni alergen: digestivni enzim iz grupe cisteinskih proteaza 5. Profesionalni alergeni: - kemikalije, biljke i životinje - češće u onih s atopijskom dijatezom, dužom izloženošću alergenu i u pušača
15 D. pteronyssinus L. destructor D. pteronyssinus G. domesticus A. siro T. putrescentiae
16 Izvor alergena III Oralni antigeni: 1. Iz hrane: 2. Lijekovi: mogući) - mehanizam nastanka kompliciran (svi tipovi alerg. reakcija - dijagnostika vrlo teška Antigeni unijeti ubodom: - male molekulske mase - većinom su hapteni - tipični lijekovi: antibiotici i anestetici - 0.4% ljudi u SAD je alergično na ubode kukaca - pčelinji otrov: 4 komponente (fosfolipaza A2) te vazoaktivne amine i peptide
17 Nomenklatura alergena Nomenklaturu predložilo Međunarodno udruženje imunoloških društava (IUIS) Glavno pravilo: Prva 3 slova roda_prvo slovo imena vrste_broj Lolium perenne Lol p 1 Dermatophagoides pteronyssiunus Der p 1 Struktura nekih alergena poznata: postoje u rekombinantnom obliku Allergen Nomenclature Committee
18 Alergijska reakcija Upalne stanice Mastociti Eozinofili Th2 limfociti... Strukturne stanice Epitelne stanice Glatko-mišićne stanice Endotelne stanice Fibroblasti Živčane stanice Medaitori Histamin, LT, PGL, PAF, NO, adenosin... Citokini IL-4, IL-5,IL-13, IL-12, TNFalfa... Kemokini Eotaxin, RANTES, MCP-4, MCP3... CCR3, CCR4
19 Patomehanizam alergijskih reakcija tipa I 19
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23 Normal larynx Laryngeal oedema
24 Tip 1
25 Što je alergija? senzibilizacija IgE- protutijela X Allergijski odgovor Rani Odgođeni i kasni Ne-IgE posredovana preosjetljivost
26 Reakcije preosjetljivosti ANAFILAKTIČKE REAKCIJE Reakcije preosjetljivosti Reakcije posredovane IgE Primjer: alergeni hrane (mlijeko, jaja, jagode,lješnjaci, orasi), lijekovi (beta-laktamski antibiotici, sulfonamidi, i sl.), otrovi insekata (pčele, ose, stršljenovi), lateks Reakcije posredovane imunokompleksima (IgG/IgM, IgA/IgG/IgM) mogu nastati na dva načina i to vezanjem na FcgI receptore te podraživanje mastocita i/ili bazofila križnim povezivanjem receptora na njihovoj površini ili aktivacijom komplementa i stvaranjem C3a/C4a/C5a anafilatoksina. Oba puta izazivaju degranulaciju i aktivaciju stanica. Primjer: reakcije na krvne derivate Izravna aktivacija komplementa inkriminiranim agensom ANAFILAKTOIDNE REAKCIJE Primjer: reakcije na membrane dijalizatora Izravan učinak na mastocite i/ili bazofile i otpuštanje medijatora, vjerojatno podraživanjem G-proteina Primjer: rtg-kontrastna sredstva, opijatni analgetici
27 Vrste reakcija preosjetljivosti
28 Oblici alergijskih reakcija
29 Alergijska reakcija tipa I 29
30 Alergen preko molekula IgE povezuje receptore za IgE što dovodi do degranulacije i oslobađanja histamina i drugih posrednika
31 Degranulacija mastocita Mirujući mastocit Degranulirani mastocit
32 Aktivacija mastocita i oslobađanje medijatora
33 Postojeći i novonastali medijatori POSTOJEĆI Histamin Lizosomalni proteini i proteaze triptaza, katepsin G, elastaza Bazični proteini bazogranulin, eozinofilni MBP, ECP Ostali enzimi b-heksozaminidaza, b-glukuronidaza eozinofilna peroksidaza NOVONASTALI Citokini IL-4, IL-8, RANTES, IL-13, MIP-1a, GM-CSF, FGF, SCF Lipidni medijatori LTC4, PAF Proteoglikani heparin, hondroitin sulfat
34 Struktura receptora visokog afiniteta za IgE
35 Prijenos signala FceRI
36 Rana alergijska reakcija
37 Rani i kasni alergijski odgovor
38 Kasna faza alergijska upala klonalna ekspanzija limfocita T na mjestu alergije upale
39 Eozinofilni medijatori,citokini i kemokini
40 Faza senzibilizacija aktivacija Th2 limfocita Kasna faza
41 Cytokine Regulation via T H 1 T H 2 Balance Th2 High affinity Between TCR and APC IFN-g High [Antigen] IL-4 IL-10 & TGF-b IL-18 IL-12 Low affinity Between TCR and APC Low [Antigen] Th1
42 Imunosna regulacija ravnoteža aktivacije subpopulacija pomoćničkih limfocita T
43 Novije spoznaje imunosne regulacije - Uloga regulacijskih T limfocita
44 Uloga regulacijskih T limfocita u kontroli imunosnog odgovora
45 Aktivacija različitih efektorskih stanica u borbi s patogenima
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47 Naslijeđivanje alergija Oba roditelja 75% 1 roditelj 50% Niti jedan od roditelja 10-15% blizanci 60%
48 Screening ljudskog genoma astma AD psorijaza Autoimunosne bolesti
49 Zašto su atopije u porastu? 1. Bolja dijagnostika i porast svijesti o alergijama 2. Genetska predispozicija 3. Psiho-socijalni utjecaji: djeca visokoobrazovanih češće alergična, manje obitelji-veća vjerojatnost 4. Izlaganje alergenima: kućni ljubimci, tapisoni 5. jungle / higijenska hipoteza
50 Higijenska hipoteza
51 Higijenska hipoteza infekcije čine razliku
52 Higijenska hipoteza Rane infekcije u djetinjstvu protektivni učinak na razvoj alergijskih bolesti
53 Hvala na pozornosti!
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