Antigén - chtf.stuba.sk

Antigén - chtf.stuba.sk

Antign je materil, ktor indukuje imunitn odpove tm, e sa viae na protiltku zvyajne ide o telu cudziu ltku skratka antibody generator (vrobca protiltok) Antigny NOSI IMUNOGNY kompletn antigny (funkn) vlastnosti DETERMINANTY imunognnos (navodenie imunitnej odpovede) antignnos (pecifickos)

TOLEROGNY antigny, ktor vaka svojmu tvaru molekuly spsobuj, e ich imunitn systm toleruje hlavne vlastn molekuly ALERGNY antign spsobujci alergick reakciu Haptny nekompletn antigny vlastnosti: antignnos (pecifickos) neimunognnos (sami o sebe nevyvolvaj imunitn odpove) rozdelenie kompletn haptny nekompletn haptny (semihaptny, inhibujce

haptny) Dkaz antignu PRIAMY DKAZ protiltka + imunogn = pozitvna reakcia kompletn haptn NEPRIAMY DKAZ protiltka + imunogn + semihaptn = negatvna reakcia kompletn haptn (inhibcia) Vlastnosti imunognu FYZIKLNE relatvna molekulov hmotnos (pribline Mr > 5000) rozpustnos: korpuskulrne (nerozpustn), koloidov (rozpustn) elektrick nboj CHEMICK

komplexnos molekuly: nosi + dostatok determinantov + biochemick truktra (primrna, sekundrna, tercirna, kvartrna) degradovatenos (najm proteny) truktrna stabilita (elatna je zl antign) BIOLOGICK cudzorodos (genetick a druhov vzdialenos) Na imunognnos vplva aj dvka, cesta vniku do organizmu, prtomnos adjuvanci a in biologick faktory (vek, hormny, genetick determincia) Chemick povaha antignov proteny toxny, biky, kapsidy vrusov, ... polysacharid lipopolysacharid, krvn skupiny, glykoproteny

nukleov kyseliny slab antign jednoduch, flexibiln, degradovaten lipidy slab antign irok distribcia, jednoduchos, truktrna nestabilnos, rchly metabolizmus Epitopy antignov determinanty SEKVENN (nepreruovan, linerne) zkladn subjednotky biopolymru (3-5) nasledujce spojito za sebou prevauj v polysacharidovch antignoch ich pecifickos sa denaturciou nemen mu sa z nosia odtiepi a sta sa haptnmi KONFORMAN (preruovan, spojen topografick) seky zkladnch subjednotiek biopolymru (12-20) z rznych miest reazca vo vzjomnej blzkosti (jedna z monch konformci) typick pre natvne proteny

ich pecifickos sa denaturciou men vinou s integrlnou sasou nosia Epitopy Schma sekvennho a konformanho antignovho determinantu tvorenho tripeptidom Tyr-Ala-Glu (TAG) Vavo polypeptid TAG-A-L, vpravo polypeptid (TAG)n: tyrozn (Tyr), alann (Ala), kyselina glutmov (Glu), polyalannov bon reazce (Poly-Ala), polylyznov skelet (Poly-Lys) T-nezvisl a T-zvisl antigny Parameter Druh antignu Vlastnosti epitopu

protenov polysacharidov lipidov natvny imunognny fragment truktra Rozpoznvan jednotka Obmedzenie molekulami MHC B-bunka + + + T-bunka +

- + zvyajne konforman + linerny peptid komplex Ag-Ab - TCR-Ag-MHC + antignov receptor T-buniek (TCR), komplex antignu a protiltky (Ag-Ab), hlavn histokompatibiln komplex (MHC)

Epitopy Schma vonho, imunopotentnho (imunognna forma) a zakrytho, imunitne nemho (neimunognna forma) antignovho determinantu Delenie antignov Rozpustnos KORPUSKULRNE (nerozpustn) KOLOIDOV (rozpustn) Chemick zloenie imunognov Typ imunognu Polypeptidy Proteny Polysacharidy Glykoproteny

Peptidoglykny Polynukleotidy Nukleoproteny Fosfolipidy Lipoproteny Lipopolysacharidy Prklad proteohormny, syntetick antigny plazmatick, mikrbne, enzmy kapsuly baktri, bunkov steny kvasiniek a hb, syntetick antigny antigny krvnch skupn, imunoglobulny, histokompatibiln antigny bunkov steny baktri DNA, RNA chromatn, ribozmy

difosfatidylglycerol, fosfatidilinozitol plazmatick, bunkov membrny bunkov obaly gramnegatvnych baktri Delenie antignov Pvod PRIRODZEN (sas rznych organizmov) SYNTETICK (umelo pripraven antigny so znmou truktrou) ARTEFICILNE (konjugovan, polosyntetick) Vzah k uritmu organizmu EXOGNNE z vonkajieho prostredia (MO a ich produkty, cudzie bunky, potraviny) ENDOGNNE sas vlastnch buniek a tkanv; mu by autoantignmi Delenie antignov Vzah medzi organizmami pri transplantcich

AUTOCHTNNE (autolgne, autoantigny) z vlastnho organizmu (sekvestrovan antigny - spermie, on oovka, tyreoglobuln) SYNGNNE/IZOGNNE od geneticky identickho jedinca toho istho druhu (jednovajcov dvojat alebo v rmci inbrednho kmea zvierat) ALOGNNE (homolgne, aloantigny, izoantigny) od geneticky neidentickho jedinca toho istho druhu (lovek-lovek) XENOGNNE (heterolgne) od jedinca fylogeneticky odlinho ivoneho druhu (zviera-lovek) Delenie antignov Mechanizmus navodenia imunitnej odpovede T-ZVISL ANTIGNY proteny vyadujce opracovanie v bunkch prezentujcich antign (APC) a spoluprcu TH- alebo TC-lymfocytov T-NEZVISL ANTIGNY polysacharidy schopn navodi priamu

tvorbu protiltok v B-lymfocytoch SUPERANTIGNY nepecificky stimuluj mnostvo klonov T- alebo B-lymfocytov ALERGNY prednostne stimuluj tvorbu IgE a tm vznik alergickch alebo hypersenzitvych reakci (proteny a glykoproteny peov, plesn, roztoov, vlukov zvierat a hmyzu, potravy) TOLEROGNY indukuj imunologick toleranciu u uritho jedinca (nevyvolvaj imunitn odpove) Superantigny Rozdiely medzi antignom a superantignom procesovanie v bunkch prezentujcich antign priama vzba na -reazec antignovho (APC), vzba v MHC liabku vyaduje V, receptora TCR (V) a sasne na -reazec J, V, D, J antignov MHC II. triedy pecifick aktivcia

T-lymfocytov nepecifick (polyklonov) aktivcia Tlymfocytov (5-25% zo vetkch klonov TH) pecifick imunitn odpove nadprodukcia cytoknov vedca k systmovej toxickosti a supresii pecifickej imunitnej odpovede Superantigny SUPERANTIGNY T-BUNIEK (zvisl od tmusu) BAKTRIOV (rozpustn exognne proteny) exotoxny G+ baktri, napr. stafylokokov enterotoxny, toxn toxickho okovho syndrmu (TSST), toxn exfoliatvnej dermatitdy supernatant mykoplazmovej artritdy

streptokokov pyrognne exotoxny VRUSOV (membrnov proteny endognnych vrusov) SUPERANTIGNY B-BUNIEK (nezvisl od tmusu) EXOGNNE napr. stafylokokov proten A ENDOGNNE napr. Fv proten (sialoproten) konzervovan asti VH-domn imunoglobulnov tvoriacich antignov receptor BCR reaguj so superantignom vznik buniek produkujcich protiltky) Superantigny Exognny a endognny superantign bunky prezentujce antigen (APC), antignov receptor Tbuniek (TCR), hlavn histokompatibiln system (MHC) Heterofiln antigny antigny s podobnmi determinantami vo fylogeneticky odlinch organizmoch,

vznik krovch reakci antigny A skupiny -hemolytickch streptokokov a udskho myokardu Forsmanov antign (morsk prasiatko, my ovca, pes, maka, hydina) Rickettsia prowasekii (kvrnit tfus) vs. Proteus vulgaris Najdleitejie antigny v ivotnom prostred MIKRBNE endotoxny gramnegatvnych baktri ERYTROCYTOV systm AB0, Rh, MNSs, P, Kell, Duffy, Lewis (spolu asi 29 skupn) HISTOKOMPATIBILN povrch vetkch jadrovch buniek loveka a inch ivochov (I. triedy) alebo len na bunkch imunitnho systmu (II. triedy) FUNKCIA urenie chemickej individuality kadho jedinca

rozpoznvanie vlastnch a cudzch alebo odcudzench antignov as pri prezentcii antignov imunokompetentnm bunkm as pri odvrhovan alotepov a inch transplantanch reakcich ANTIGNY SPOJEN S NDORMI LEUKOCYTOV Lipopolysacharid (LPS) GlcN OPAKUJCE SA OLIGOSACHARIDY GlcN MASTN KYSELINY

P P LIPID A kyselina 2-keto-3deoxyoktnov (KDO) R-PECIFICKOS JADROV OLIGOSACHARID O-PECIFICKOS POLYSACHARIDOV BON REAZEC monosacharidy: glukza, galaktza, N-acetylglukzamn, N-acetylgalaktzamn, ramnza 3,6-dideoxyhexzy: abequza, kolitza,

paratza, tyvelza urnov kyseliny Jeden monosacharid v kadej oligosacharidovej jednotke je IMUNODOMINANTN SOMATICK O-ANTIGN LPS POLYSACHARID LIPID A LIPID B PROTEN

Biologick inky LPS pyrognnos (zvyovanie telesnej teploty) znenie tlaku krvi (endotoxnov ok pri vej dvke LPS) aktivcia nepecifickej imunity: komplementu a makrofgov (zpal) koagulcia t.j. agregcia trombocytov leukopnia (< 5000/mm3), leukocytza (> 10000/mm3)

mitognna aktivita na B-lymfocyty my imunoadjuvantn inok na tvorbu protiltok stimulcia tvorby cytoknov (TNF-, IFN, IL-1) indukuje loklnu alebo systmov Schwartzmanovu reakciu Erytrocytov antigny Krvn skupiny systmu AB0 (H) Fenotyp Antigny na erytrocytoch (aglutinny) Genotyp Srov protiltky (izohemaglutinny)

0 00 H (0) anti-A a anti-B A AA alebo A0 A = H (0) + N-acetylglukzamn anti-B B

BB alebo B0 B = H (0) + D-galaktza anti-A AB AB AaB iadne Reakcie erytrocytov s antisrami proti krvnm skupinm AB0 Erytrocyty

Antisrum 0 A B AB 0 - - -

- A + - + - B +

+ - - AB + + + - Erytrocytov antigny

Erytrocytov antigny Rh SYSTM sbor antignov na povrchu erytrocytov ud a opc Macaccus rhesus resp. mulata; ktor s kdovan na chromozme 1 (alelov pry Dd, Cc, Ee a in) Rh- pozitvny (RhD+) 85% jedincov s antignom D Rh-negatvny (RhD-) 15% jedincov bez antignu D Nepriamy Coombsov test (nepriamy antiglobulnov test) Vznik hemolytickej choroby novorodencov

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