{"id":10148,"date":"2020-04-23T04:57:59","date_gmt":"2020-04-23T01:57:59","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/imunofenotipare-limfocitara-profil-de-baza\/"},"modified":"2025-07-22T15:24:54","modified_gmt":"2025-07-22T12:24:54","slug":"imunofenotipare-limfocitara-profil-de-baza","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/imunofenotipare-limfocitara-profil-de-baza\/","title":{"rendered":"\u041b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u0430\u0440\u043d\u043e\u0435 \u0438\u043c\u043c\u0443\u043d\u043e\u0444\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 - \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u0439 \u043f\u0440\u043e\u0444\u0438\u043b\u044c"},"content":{"rendered":"

Informa\u0163ii generale despre sistemul imun<\/span><\/strong><\/em><\/p>\n

Func\u0163ia primar\u0103 a sistemului imun este aceea de a lupta \u00eempotriva agen\u0163ilor patogeni microbieni (bacterii, parazi\u0163i, fungi, virusuri). Sistemul imun \u00eendepline\u015fte aceast\u0103 func\u0163ie \u00een dou\u0103 moduri: \u00een primul r\u00e2nd, prin generarea unui r\u0103spuns imun specific \u00eempotriva agentului patogen invadant \u015fi controlul infec\u0163iei;\u00a0\u00een al doilea r\u00e2nd, prin reamintirea acestui prim \u201cconflict\u201d \u015fi declan\u015farea unui r\u0103spuns imun accelerat \u00een urma reexpunerii la acela\u015fi agent patogen microbian3<\/sup>.<\/span><\/p>\n

Sistemul imun este constituit dintr-o re\u0163ea complex\u0103 de celule, \u0163esuturi \u015fi organe care particip\u0103 \u00eempreun\u0103 la ap\u0103rarea organismului uman.<\/span><\/p>\n

Cunoa\u015fterea structurii \u015fi func\u0163iei complexe a sistemului imun ajut\u0103 la \u00een\u0163elegerea fundamentului deficien\u0163elor imune congenitale sau dob\u00e2ndite (infec\u0163ia HIV) \u015fi la perceperea c\u0103ilor poten\u0163iale prin care sistemul imun poate fi modulat \u00een cazul unor boli specifice3;9<\/sup>.<\/span><\/p>\n

Organele limfoide ale sistemului imun sunt: m\u0103duva osoas\u0103 hematogen\u0103 (situsul hematopoiezei), timusul (centrul \u201cinstructajului timic\u201d, de maturare a protimocitelor in celule T mature), splina (\u201efiltrul\u201d imunologic al s\u00e2ngelui), nodulii limfatici (centrul imunologic al limfei), \u0163esutul limfoid asociat mucoaselor (MALT) \u015fi \u0163esutul limfoid asociat tractului digestiv (GALT)9;11<\/sup>. Intr-o manier\u0103 similar\u0103, macrofagele \u015fi celulele dendritice de la nivelul splinei \u015fi nodulilor limfatici captureaz\u0103 antigenele \u015fi le prezint\u0103 limfocitelor B \u015fi T, declan\u015f\u00e2nd astfel r\u0103spunsul imun.<\/span><\/p>\n

Celulele sistemului imun sunt: limfocitele T, limfocitele B, celulele NK, granulocitele, macrofagele\/monocitele, fibrobla\u015ftii, celulele epiteliale, celulele dendritice3;9<\/sup>.<\/span><\/p>\n

Majoritatea agen\u0163ilor patogeni au o capacitate de proliferare foarte ridicat\u0103, iar prevenirea infec\u0163iilor sistemice necesit\u0103 r\u0103spunsuri adecvate \u015fi rapide din partea sistemului imun \u00eenn\u0103scut \u015fi a sistemului imun dob\u00e2ndit11<\/sup>.<\/span><\/p>\n

Imunitatea nespecific\u0103\/\u00eenn\u0103scut\u0103 asigur\u0103 prima linie de ap\u0103rare \u00eempotriva agen\u0163ilor microbieni patogeni11<\/sup>.<\/span><\/p>\n

Se caracterizeaz\u0103 prin r\u0103spunsuri imune nespecifice, rapide \u015fi la fel de intense, indiferent de tipul agentului patogen, care destul de rar sunt suficiente pentru a elimina\u00a0\u00een totalitate infec\u0163iile microbiene celulare \u015fi prin lipsa memoriei imunologice sau a unei imunit\u0103\u0163i protective de durat\u0103. Este asigurat\u0103 prin intermediul barierelor anatomice (tegumente, membrane, mucoase), barierelor fiziologice (temperatura, pH), factorilor chimici (interferoni, sistemul complement), celulelor cu activitate fagocitar\u0103 (macrofage\/monocite, celule dendritice, neutrofile, fibrobla\u015fti, celule epiteliale), citotoxicita\u0163ii mediate celular (celulele NK)3;9<\/sup>.<\/span><\/p>\n

Prin produc\u0163ia de mediatori (citokine, chemokine, interferoni), r\u0103spunsurile imune nespecifice stabilesc \u201cscena\u201c pentru declan\u015farea r\u0103spunsurilor imune specifice11<\/sup>.<\/span><\/p>\n

Imunitatea specific\u0103\/dob\u00e2ndit\u0103\/adaptativ\u0103 este acea func\u0163ie a sistemului imun de a recunoa\u015fte specific antigenele \u015fi de a dezvolta o imunitate mediat\u0103 umoral, o imunitate mediat\u0103 celular sau ambele, principalii \u201c juc\u0103tori\u201d fiind anticorpii, limfocitele B, limfocitele T \u015fi celulele prezentatoare de antigen. Acest tip de imunitate poate fi dob\u00e2ndit\u0103 activ (organismul gazd\u0103 produce proprii anticorpi\/limfocite imunologic active, iar imunitatea este de lung\u0103 durat\u0103) sau pasiv (organismul prime\u015fte anticorpi\/limfocite imunologic active produse \u00een timpul unui r\u0103spuns imunologic activ \u00een alt organism, iar imunitatea este de scurt\u0103 durat\u0103). Indiferent c\u0103 este vorba despre o imunitate activ\u0103 sau pasiv\u0103, aceasta poate fi dob\u00e2ndit\u0103 natural (anticorpii sunt produ\u015fi\u00a0\u00een organismul gazd\u0103 sau primi\u0163i prin transfer placentar\/al\u0103ptare) sau artificial (prin vaccinare)9<\/sup>.<\/span><\/p>\n

O carateristic\u0103 important\u0103 a acestui tip de imunitate este memoria imunologic\u0103<\/span>.<\/span><\/p>\n

R\u0103spunsurile imune adaptative sunt larg extinse prin stimulare antigenic\u0103, ceea ce conduce la expansiunea clonal\u0103, diferen\u0163ierea \u015fi maturarea a diverse clone de celule B antigen specifice, pentru a produce anticorpi circulan\u0163i (r\u0103spuns imun umoral), \u015fi prin activarea celulelor T, derivate din timus, la r\u0103spunsuri imune celulare antigen specifice. Practic, imunitatea adaptativ\u0103 depinde de re\u0163eaua de interac\u0163iuni foarte complexe \u015fi intricate dintre diferitele tipuri celulare \u015fi subseturile lor, reglate prin produc\u0163ia lor de mediatori (citokine, chemokine si interferoni tip I,II )11<\/sup>.<\/span><\/p>\n

Celulele sistemului imun \u00eenn\u0103scut constituie o rezerv\u0103 celular\u0103 uniform\u0103 f\u0103r\u0103 specificitate antigenic\u0103; pot fi recrutate \u00een num\u0103r remarcabil de mare; sunt primele care ajung la locul infec\u0163iei; modelul de migrare este unidirec\u0163ional, iar odat\u0103 exercitat\u0103 func\u0163ia lor, celulele vor fi eliminate. \u00cen cazul celulelor specifice sistemului imun dob\u00e2ndit (limfocitele), acestea sunt prezente \u00eentr-un num\u0103r sc\u0103zut pentru un anumit antigen \u015fi, pentru a contrabalansa acest dezavantaj, ele urmeaz\u0103 un mod complex de migrare, str\u00e2ns dependent de statusul lor de activare \u015fi memorie imunologic\u0103. Prezint\u0103 deci capacitatea de a recircula: reintr\u0103 \u00een circula\u0163ia sangvin\u0103 de la nivelul \u0163esuturilor limfoide\u00a0\u015fi migreaz\u0103 c\u0103tre un situs la distan\u0163\u0103. Migrarea limfocitelor este bine organizat\u0103 pentru a asigura o expunere eficient\u0103 a acestora la antigenele lor \u00eenrudite de la nivelul organelor limfoide secundare. Mai mult, clonele limfocitare care prezint\u0103 anumite caracteristici relevante, cum ar fi receptorii care recunosc epitopii antigenici, nu sunt pierdute dup\u0103 implicarea \u00een r\u0103spunsul imun, \u00een schimb sunt rezervate ca \u201ccelule cu memorie\u201d pentru a asigura r\u0103spunsuri imune specifice mai rapide \u015fi mai puternice, \u00een cazul reinfec\u0163iei cu acela\u015fi agent patogen11<\/sup>.<\/span><\/p>\n

Celulele prezentatoare de antigen (APC) reprezint\u0103 un grup de celule heterogen din punct de vedere morfologic \u015fi func\u0163ional, provin din precursori medulari \u015fi sunt specializate \u00een a prezenta antigenele limfocitelor, \u00een special celulelor T. Aceste celule profesionale prezentatoare de antigen includ monocite (prezente \u00een s\u00e2ngele periferic), macrofage (monocite tisulare), celule rezidente de la nivelul organelor limfoide ale sistemului imun (celule dendritice) \u015fi constituen\u0163i ai sistemului monocit-macrofag din alte organe solide. Limfocitele B, care capteaz\u0103 antigenul prin intermediul receptorilor de tip mIg (imunoglobuline de membran\u0103), pot de asemenea s\u0103 func\u0163ioneze eficient ca APC pentru limfocitele T, prin prezentarea antigenului degradat (oligopeptid) legat de moleculele complexului major de histocompatibilitate (MHC); limfocitele T activate vor secreta citokine care vor dirija diferen\u0163ierea limfocitelor B \u015fi produc\u0163ia de anticorpi a acestora. Caracteristica definitorie a acestor celule este exprimarea moleculelor MHC I \u015fi II pe suprafa\u0163a lor, precum \u015fi a moleculelor accesorii necesare pentru activarea limfocitelor T: CD86 \u015fi CD80. Imediat dup\u0103 activare, APC pot sa secrete citokine care induc func\u0163ii specifice \u00een celulele c\u0103rora le prezint\u0103 antigenul. Monocitele \u015fi macrofagele sunt fagocitic active, exercitand aceast\u0103 func\u0163ie \u00een special asupra antigenelor acoperite de anticorpi sau de componente ale sistemului complement care se leag\u0103 de receptorii de suprafa\u0163\u0103 pentru Fc\u03b3 \u015fi C3b11;12<\/sup>.<\/span><\/p>\n

Moleculele de legare a antigenelor, prin capacitatea lor de a lega antigenele str\u0103ine organismului uman, sunt responsabile de specificitatea r\u0103spunsului imun dob\u00e2ndit. Exist\u0103 trei seturi de astfel de molecule: imunoglobuline (Ig), receptorul celulelor T (TCR) \u015fi moleculele MHC<\/span>, toate aceste molecule f\u0103c\u00e2nd parte din superfamilia de imunoglobuline (IgSF). Ig sunt alc\u0103tuite dintr-un lan\u0163 polipetidic greu (H) \u015fi un lan\u0163 usor (L), de tip kappa sau lambda; acestea sunt exprimate pe suprafa\u0163a limfocitelor B \u015fi secretate ca anticorpi \u00een cadrul r\u0103spunsului imun umoral. TCR se prezint\u0103 sub forma unui heterodimer alc\u0103tuit din 2 lan\u0163uri polipeptidice H \u2013 \u03b1\u03b2\/\u03b3\u03b4; majoritatea limfocitelor T exprim\u0103 \u03b1\u03b2-TCR. Genele HLA situate pe cromozomul 6 codific\u0103 moleculele complexului major de histocompatibilitate MHC I \u015fi II. Moleculele MHC I sunt formate dintr-un singur lan\u0163 H (HLA-A, B, C), spre deosebire de moleculele MHC II care sunt alc\u0103tuite din dou\u0103 lan\u0163uri H \u2013 \u03b1 \u015fi \u03b2 (HLA-DQ, DR, DP). Limfocitele T care exprim\u0103 pe suprafa\u0163a lor receptori \u03b1\u03b2-TCR pot fi divizate \u00een dou\u0103 subpopula\u0163ii majore. Aceast\u0103 \u00eemp\u0103r\u0163ire este bazat\u0103 pe clasa de molecule MHC recunoscut\u0103 de receptorii \u03b1\u03b2-TCR \u015fi de expresia moleculelor CD4 sau CD8, care prin ata\u015farea de moleculele MCH contribuie la completarea leg\u0103turii moleculare intercelulare. In timp ce limfocitele CD4 recunosc antigenul legat de moleculele MHC I, limfocitele CD8 recunosc antigenul legat de moleculele MCH II; raportul limfocitelor CD4\/CD8 \u00een s\u00e2ngele periferic este aproximativ 2:1 (0.8:1-3:1). Toate celulele nucleate exprim\u0103 molecule MHC I \u015fi sunt APC non-profesionale, APC profesionale exprim\u00e2nd molecule MHC II. Interac\u0163iunea dintre complexul MHC-peptidul antigenic \u015fi TCR de\u0163ine un rol esen\u0163ial \u00een protec\u0163ia imun\u0103, deoarece un r\u0103spuns imun complet necesit\u0103 interven\u0163ia celulelor T antigen specifice. Acesta reprezint\u0103 practic un mecanism de siguran\u0163\u0103 pentru a minimaliza posibila auto-reactivitate (reactivitate \u00eempotriva self-ului), astfel \u00eenc\u00e2t un limfocit T devine activat numai pentru c\u0103 a \u00eent\u00e2lnit un antigen str\u0103in (non-self).<\/span><\/p>\n

Limfocitele B provin din celulele stem hematopietice care, \u00een mod succesiv, populeaz\u0103 splahnopleura embrionar\u0103 paraaortic\u0103, ficatul fetal \u015fi m\u0103duva osoas\u0103 hematogen\u0103. Celulele stem fiice dau na\u015ftere progenitorilor limfoizi multipotenti (PLM), care genereaz\u0103 celulele mieloide sau limfoide. Astfel, PLM pot produce precursorii limfoizi comuni (PLC), iar ace\u015ftia pot genera limfocitele T, limfocitele B, celulele NK \u015fi un subset special de celule dendritice. Diferen\u0163ierea final\u0103 spre celulele B necesit\u0103 ca celulele fiice PLC s\u0103 fie expuse unor micromedii specializate, a\u015fa cum sunt cele prezente \u00een ficatul fetal \u015fi m\u0103duva osoas\u0103. Trecerea de la ficatul fetal la m\u0103duva osoas\u0103 \u00eencepe la mijlocul vie\u0163ii fetale \u015fi se termin\u0103 chiar \u00eenainte de na\u015ftere; celulele B continu\u0103 s\u0103 fie produse \u00een m\u0103duva osoas\u0103 pe parcursul intregii vie\u0163i. Diferen\u0163ierea celulelor B are loc \u00een dou\u0103 stadii, diferite din punct de vedere anatomic \u015fi func\u0163ional; astfel, primul stadiu are loc\u00a0\u00een m\u0103duva osoas\u0103 \u015fi este antigen independent, iar cel de-al doilea stadiu are loc \u00een organele limfoide periferice \u015fi este antigen dependent9;11<\/sup>.<\/span><\/p>\n

Limfocitele B imature, care exprim\u0103 pe suprafa\u0163a lor mIgM (imunoglobulina de membran\u0103) \u015fi BCR (receptorul celulei B), p\u0103r\u0103sesc m\u0103duva osoas\u0103 dup\u0103 un proces de selec\u0163ie negativ\u0103 a celulelor B auto-reactive \u015fi p\u0103trund \u00een periferie (s\u00e2nge \u015fi organe limfoide secundare) unde \u00ee\u015fi completeaz\u0103 diferen\u0163ierea \u00een celule B mature care exprim\u0103 pe suprafa\u0163a lor mIgM \u015fi mIgD \u015fi pot fi activate prin legarea de antigen11<\/sup>.<\/span><\/p>\n

Celulele B imature auto-reactive, ce exprim\u0103 mIgM self-reactiv, urmeaz\u0103 un proces cunoscut ca \u201creceptor editing\u201c, \u00een care un rearanjament la nivelul genelor care codific\u0103 lan\u0163ul greu al imunoglobulinelor (IgH) modific\u0103 specificitatea antigenic\u0103 a receptorului. Dac\u0103 acest proces e\u015fueaz\u0103, celulele B imature auto-reactive devin anergice sau vor suferi apoptoza \u00een urma contactului cu antigenul. Aceasta contrasteaz\u0103 cu abilitatea celulelor B mature de a deveni activate \u00een urma contactului antigenic12<\/sup>.<\/span><\/p>\n

BCR este un complex format dintr-o mIg \u015fi dou\u0103 molecule citoplasmatice Ig\u03b1\/CD79a \u015fi Ig\u03b2\/CD79b. Cu ajutorul acestui receptor limfocitele B recunosc antigenul \u015fi devin astfel activate. Implicarea BCR ini\u0163iaz\u0103 o serie de evenimente care culmineaz\u0103 cu diferen\u0163ierea celulelor B \u00een plasmocite capabile s\u0103 secrete imunoglobuline. Limfocitele B vor prezenta antigenul, recunoscut cu ajutorul BCR, limfocitelor T helper CD4 care au fost activate anterior de acela\u015fi antigen, \u00a0limfocitele T helper fiind selectate din pool-ul de limfocite T naive de c\u0103tre celulele dendritice prezentatoare de antigen. Acest proces de activare a limfocitelor B, dependent de limfocitele T, are loc prin interac\u0163iunea dintre CD40 de pe suprafa\u0163a celulelor B \u015fi ligandul sau, CD145, de pe suprafa\u0163a celulelor T helper \u015fi prin secre\u0163ia de interleukina-4 (IL-4) de c\u0103tre celulele helper. Ambele semnale servesc la promovarea \u015fi men\u0163inerea activ\u0103rii ini\u0163iate de BCR11<\/sup>.<\/span><\/p>\n

La nivelul organelor limfoide secundare \u2013 \u00een zonele bogate \u00een celule T \u2013 celulele B naive, dup\u0103 stimularea antigenic\u0103, urmeaz\u0103 o expansiune clonal\u0103 \u015fi formeaz\u0103 grupuri de celule B activate (focare extrafoliculare). Acestea se pot diferen\u0163ia \u00een plasmocite de scurt\u0103 durat\u0103 (secretoare de anticorpi cu afinitate joas\u0103) sau migreaz\u0103 \u00eenapoi \u00een foliculi \u015fi ini\u0163iaz\u0103 formarea unui centru germinativ.<\/span><\/p>\n

Dup\u0103 proliferare \u015fi matura\u0163ie, celulele B din centrul germinativ se pot diferen\u0163ia \u00een plasmocite de lung\u0103 durat\u0103 \u015fi celule B de memorie. Majoritatea plasmocitelor de lung\u0103 durat\u0103 migreaz\u0103 \u00een m\u0103duva osoas\u0103 \u015fi sunt r\u0103spunz\u0103toare de men\u0163inerea nivelului seric de anticorpi (anticorpi de \u00eenalt\u0103 afinitate); celulele B de memorie pot r\u0103m\u00e2ne pentru o lung\u0103 perioad\u0103 de timp la nivelul organelor limfoide secundare sau pot migra \u015fi habita \u00een m\u0103duva osoas\u010311;12<\/sup>. \u00cen urma contactului antigenic, celulele B de memorie r\u0103spund printr-o proliferare rapid\u0103 \u015fi diferen\u0163iere \u00een plasmocite, ref\u0103c\u00e2nd astfel rezerva de celule B de memorie \u015fi plasmocite.<\/span><\/p>\n

Prin dezvoltarea tehnologiei anticorpilor monoclonali, analiza anumitor molecule de pe suprafa\u0163a celulelor B (CD = \u201ccluster determinants\u201d) a ajutat la definirea stadiilor care se succed pe parcursul \u00eentregului proces de diferen\u0163iere \u015fi matura\u0163ie a celulelor B (vezi tabelul 17.9.1.1):<\/span><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/span><\/td>\nCelule Stem<\/span><\/td>\nCelule Pro-B<\/span><\/td>\nCelule Pre-B<\/span><\/td>\nCelule pre-Blate<\/span><\/td>\nCelule B imature<\/span><\/td>\nCelule B mature<\/span><\/td>\nCelule B activate<\/span><\/td>\nPlasmocite<\/span><\/td>\nCelule B de memorie<\/span><\/td>\n<\/tr>\n
CD34<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n<\/tr>\n
CD10<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n<\/tr>\n
CD19<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n<\/tr>\n
CD20<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n<\/tr>\n
CD21<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0<\/span><\/td>\n<\/tr>\n
CD24<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0 +<\/span><\/td>\n\u00a0<\/span><\/td>\n<\/tr>\n
CD38<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n<\/tr>\n
CD27<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n\u00a0 ++<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Tabel 17.9.1.1 Markeri pentru diferen\u0163ierea celulelor B<\/span><\/em><\/p>\n

Limfocitele T citotoxice (CTL) \u015fi celulele NK<\/strong><\/span><\/p>\n

Aceste dou\u0103 tipuri celulare, distincte din punct de vedere fenotipic, dar str\u00e2ns legate prin func\u0163ia lor citolitic\u0103 (\u201ckiller\u201d), sunt importante at\u00e2t \u00een controlul infec\u0163iilor, c\u00e2t \u015fi \u00een identificarea\u00a0\u015fi eliminarea celulelor tumorale. Celulele CTL sunt limfocite T CD8+ care \u00ee\u015fi \u00eendeplinesc func\u0163ia de \u201ckiller\u201c prin dou\u0103 c\u0103i majore: liza mediat\u0103 de perforine\u00a0\u015fi granzime ce sunt eliberate din lizozomi\u00a0\u015fi apoptoza receptor indus\u0103 (TNFR), ambele c\u0103i necesit\u00e2nd un contact apropriat \u00eentre celula litic\u0103\u00a0\u015fi \u0163inta sa, \u00een special prin interac\u0163iunea dintre TCR\u00a0\u015fi moleculele MHC I. R\u0103spunsul CTL la o infec\u0163ie acut\u0103 are loc \u00een trei faze: prima const\u0103 \u00een activarea ini\u0163ial\u0103\u00a0\u015fi proliferarea CTL; a doua \u00een contrac\u0163ia celulelor T efectoare \u00een celule T de memorie; iar a treia faz\u0103 se refer\u0103 la men\u0163inerea de lung\u0103 durat\u0103 a pool-ului de celule T de memorie. Celulele CTL se dezvolt\u0103 la nivelului timusului, p\u0103r\u0103sesc acest organ limfoid \u00een stare naiv\u0103, circul\u0103 \u00eentre organele limfoide secundare (splina\u00a0\u015fi ganglionii limfatici) pe calea sistemului arterial, respectiv limfatic,\u00a0\u015fi \u00een cursul acestui pasaj \u00eent\u00e2lnesc antigenul nonself. Antigenul este adus la nivelul organelor limfoide secundare prin sistemul limfatic de c\u0103tre celula dendritic\u0103 (APC); aceasta devine matur\u0103 dup\u0103 achizi\u0163ia antigenului nonself la nivelul \u0163esuturilor non-limfoide. De\u015fi celula dendritica este cel mai important APC profesional, macrofagele\u00a0\u015fi celulele B sunt de asemenea capabile s\u0103 prezinte antigenul. Procesul infec\u0163ios conduce la o cre\u015ftere dramatic\u0103 a CTL patogen\/antigen specifice, iar magnitudinea acestui proces depinde de natura infec\u0163iei\u00a0\u015fi de inoculul\/doza de antigen. Aceast\u0103 expansiune este urmat\u0103 de \u00a0contrac\u0163ia CTL efectoare \u00een celule T de memorie. Un procent de 5% din popula\u0163ia celulelor efectoare expansionate supravie\u0163uie\u015fte sub forma celulelor de memorie de lung\u0103 durat\u0103. Este prevenit\u0103 astfel afectarea tisular\u0103 nespecific\u0103 ce se poate produce prin activitatea citolitic\u0103 \u015fi eliberarea necontrolat\u0103 de citokine \u015fi este asigurat\u0103 flexibilitatea CTL de a r\u0103spunde la noi infec\u0163ii.<\/span><\/p>\n

Produc\u0163ia de celule de memorie antigen, independent\u0103 de lung\u0103 durat\u0103 este esen\u0163ial\u0103 pentru un r\u0103spuns rapid \u00een cazul unei reinfec\u0163ii. CTL de memorie asigur\u0103 un r\u0103spuns mult mai intens dec\u00e2t celulele CTL naive activate primar, at\u00e2t din punct de vedere cantitativ c\u00e2t si calitativ. Deoarece \u00een cursul infec\u0163iei primare CTL sufer\u0103 o expansiune clonal\u0103 important\u0103, num\u0103rul de precursori CTL antigen specifici este mult mai mare la indivizii imuniza\u0163i comparativ cu cei naivi, ceea ce permite un r\u0103spuns imun mai puternic. CTL de memorie prezint\u0103 o eficien\u0163\u0103 extraordinar\u0103 \u00een elaborarea func\u0163iilor efectoare prin produc\u0163ia rapid\u0103 de gamma-interferon (IFN\u03b3).<\/span><\/p>\n

Compartimentul CTL de memorie este compus din dou\u0103 tipuri celulare: CTL de memorie-efectoare (Tem) \u015fi CTL de memorie-centrale (Tcm), acestea din urm\u0103 fiind capabile de o auto-reinnoire antigen-independent\u0103 homeostatic\u0103 prelungit\u0103. La \u00eent\u00e2lnirea cu antigenul, aceste celule dob\u00e2ndesc rapid func\u0163ia efectoare \u015fi fenotipul celulelor Tem. Celulele CD4 \u015fi citokinele IL-15, IL-7, IL-2 \u015fi GM-CSF (factorul de stimulare al coloniilor pentru granulocite \u015fi monocite) au un rol important \u00een supravie\u0163uirea \u015fi men\u0163inerea rezervei de CTL de memorie (vezi tabelul 17.9.1.2).<\/span><\/p>\n

\u00cen final, activitatea citotoxica a CTL are loc prin dou\u0103 mecanisme:<\/span><\/p>\n

\u2022 citolitic<\/span>: dependent de produc\u0163ia de granzime (A, B) si perforine;<\/span><\/div>\n
\u2022 non-citolitic<\/span>: dependent de produc\u0163ia de citokine (IFN\u03b3 si TNF-\u03b1) care au capacitatea de a inhiba proliferarea agen\u0163ilor patogeni intracelulari11;12<\/sup>.<\/span><\/div>\n
<\/div>\n\n\n\n\n\n\n\n
\u00a0\u00a0\u00a0\u00a0\u00a0 MARKER<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 CTL naive<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Tem<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Tcm<\/span><\/td>\n<\/tr>\n
CD44<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 +<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 +++<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 +++<\/span><\/td>\n<\/tr>\n
Distribu\u0163ia tisulara principala<\/span><\/td>\nGanglioni limfatici, splina, sange<\/span><\/td>\nTesuturile non-limfoide (plaman, ficat), splina<\/span><\/td>\nGanglioni limfatici, splina, sange<\/span><\/td>\n<\/tr>\n
Func\u0163ia citotoxica<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 -<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 ++<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 -<\/span><\/td>\n<\/tr>\n
IFN\u03b3<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 -<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 +++<\/span><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 +<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0Tabel\u00a0 17.9.1.2 Propriet\u0103\u0163ile CTL<\/span><\/em><\/p>\n

Celulele NK apar\u0163in liniei celulare limfoide \u015fi sunt implicate \u00een r\u0103spunsul imun \u00eenn\u0103scut. \u00cen compara\u0163ie cu CTL, celulele NK sunt de talie relativ mare, granulare \u015fi nu necesit\u0103 pre-activare pentru a recunoaste \u015fi a liza celule tumorale sau aberante. De asemenea nu au nevoie de prezen\u0163a moleculelor MHC I. Aceste celule sunt capabile s\u0103 produc\u0103 cantit\u0103\u0163i importante de citokine \u015fi chemokine, care le permit s\u0103 moduleze r\u0103spunsul imun. IL-15 este necesar\u0103 pentru a men\u0163ine nivelul homeostatic al celulelor NK in organism, activitatea de \u201ekiller\u201d fiind exercitat\u0103 \u00een acela\u015fi \u00a0mod ca \u015fi \u00een cazul CTL.<\/span><\/p>\n

Receptorii celulelor NK sunt clasifica\u0163i \u00een activatori si inhibitori \u015fi apar\u0163in la dou\u0103 familii importante de receptori: killer cell immunoglobulin-like (KIR) \u015fi lectin-like. Prin receptorii inhibitori celulele NK recunosc moleculele MHC I de pe suprafa\u0163a celulei \u0163int\u0103 \u015fi primesc astfel un semnal inhibitor \u2013 no-killing; prin receptorii activatori recunosc liganzi celulari, virali sau indu\u015fi de stres, care transmit un semnal activator \u2013 pro-killing. In cazul \u00een care o celul\u0103 \u0163int\u0103 nu exprim\u0103 moleculele MHC I pentru a evita ac\u0163iunea citolitica a CTL, aceasta va fi distrus\u0103 de c\u0103tre celula NK.<\/span><\/p>\n

Celulele NK se afla \u00eentr-un num\u0103r relativ redus la nivelul m\u0103duvei osoase \u015fi splinei (<2%) \u015fi reprezint\u0103 aproximativ 15% din num\u0103rul total de limfocite din s\u00e2nge. NK sunt de obicei definite prin intermediul unei combina\u0163ii de markeri de suprafa\u0163a celular\u0103 (CD): CD3-, CD16+, CD56+. Astfel pot fi clasificate \u00een dou\u0103 subseturi, \u00een func\u0163ie de exprimarea CD16 \u015fi CD56:<\/span><\/p>\n

\u2022 NKCD56dimCD16bright reprezint\u0103 >90% din NK din s\u00e2ngele periferic, exprim\u0103 nivele mari de KIR \u015fi activitate citotoxic\u0103\/citolitic\u0103 mare (secre\u0163ie crescut\u0103 de perforine\/granzime);<\/span><\/div>\n
\u2022 NKCD56brightCD16dim se caracterizeaz\u0103 printr-o produc\u0163ie mai mare de citokine, poten\u0163ial proliferativ mai \u00eenalt \u015fi reprezint\u0103 principala popula\u0163ie celular\u0103 NK de la nivelul organelor limfoide secundare11;12<\/sup>.<\/span><\/div>\n

Celulele T helper-CD4, \u00een mod similar celulelor TCR+, se diferen\u0163iaz\u0103 la nivelul timusului din celulele progenitoare comune limfoide, \u00een cea mai mare parte \u00een timpul vie\u0163ii fetale \u015fi imediat dup\u0103 na\u015ftere. Ini\u0163ial, celulele T nu exprim\u0103 TCR \u015fi sunt CD3-\/CD4-\/CD8- (triplu negative). Etapele de diferen\u0163iere timic\u0103 includ stadiile:<\/span><\/p>\n

\u2022 preTCR CD3+\/CD4-\/CD8- (dublu negative);<\/span><\/div>\n
\u2022 TCR CD3+\/CD4+\/CD8+ (dublu pozitive);<\/span><\/div>\n
\u2022 \u00een ultima etap\u0103, celulele T al c\u0103ror TCR recunoa\u015fte antigenul prezentat de moleculele MHC II devin TCR CD3+\/CD4+, iar cele al c\u0103ror TCR recunoa\u015fte antigenul prezentat de moleculele MHC I devin TCR CD3+\/CD8+.<\/span><\/div>\n

Celulele T naive, pozitive pentru un singur CD (CD4 sau CD8) p\u0103r\u0103sesc timusul \u015fi recircul\u0103 din s\u00e2nge \u00een ariile timus-dependente (TDA) ale organelor limfoide secundare. \u00cen majoritatea r\u0103spunsurilor imune, activarea celulelor T CD4+ are loc \u00een TDA ale organelor limfoide secundare, iar celulele prezentatoare de antigen sunt reprezentate de celulele dendritice. Prezentarea eficient\u0103 a antigenului non-self stimuleaz\u0103 activarea, proliferarea \u015fi diferen\u0163ierea limfocitelor CD4+ \u00een trei categorii func\u0163ionale: celule CD4+ cu activitate\u00a0proinflamatorie, celule CD4+ cu activitate reglatoare\/antiinflamatorie \u015fi celule CD4+ ce func\u0163ioneaz\u0103 ca celule de memorie. Diferen\u0163ierea dintre celulele T naive, efectoare \u015fi de memorie se face pe\u00a0baza moleculelor exprimate pe suprafa\u0163a lor (vezi tabelul 17.9.1.3).<\/span><\/p>\n

Celulele CD4+ efectoare sunt cele care sus\u0163in procesele inflamatorii prin eliberarea de citokine, fiind divizate \u00een trei categorii: Th1 , Th2, Th1711;12<\/sup>.<\/span><\/p>\n

Celulele T reglatoare (Treg)<\/span><\/strong><\/p>\n

Pentru a preveni r\u0103spunsurile imune auto-distructive \u015fi a permite cele protective \u00eempotriva antigenelor non-self, sistemul imun a dezvoltat o serie de mecanisme reglatoare care au rolul de a inhiba generarea de limfocite T \u015fi B self-reactive poten\u0163ial d\u0103un\u0103toare \u2013 toleran\u0163a imun\u0103 central\u0103 \u2013 \u015fi de a sc\u0103dea activarea celular\u0103 \u015fi expansiunea limfocitelor atunci c\u00e2nd acestea \u00eent\u00e2lnesc antigene self \u2013 toleran\u0163a imun\u0103 periferic\u0103.<\/span><\/p>\n

Au fost descrise mai multe tipuri de celule T cu activitate reglatoare: celule T TCR\u03b3\u03b4 +, celule NK, limfocite T CD8+ \u015fi limfocite T CD4+.<\/span><\/p>\n

Celulele T CD4+ reg pot fi divizate \u00een dou\u0103 categorii: celulele Treg care apar natural (generate \u00een timus) \u015fi celulele Treg induse (Treg 1 care secret\u0103 IL-10, Th3 care secret\u0103 TGF\u03b2), diferen\u0163iate din celulele T naive. Celulele T CD4+ reg\u00a0derivate din timus sunt CD25+ \u015fi se g\u0103sesc \u00eentr-un procent de 30%, \u00eens\u0103 doar 2-4% din celule Treg CD25high+ au propriet\u0103\u0163i supresive. Un alt marker important este factorul de transcrip\u0163ie FOXP3 care este exprimat \u00een mod specific la nivelul celulele Treg timic derivate. Majoritatea celulelor FOXP3 + sunt celule CD4+CD25 bright+ \u015fi doar c\u00e2teva sunt celule CD25- \u015fi CD25 low+11<\/sup>.<\/span><\/p>\n

Celulele T de memorie<\/strong> <\/span><\/p>\n

Nivelul protec\u0163iei imune se coreleaz\u0103 cu num\u0103rul de celule T de memorie antigen specifice. In cursul infec\u0163iei primare exist\u0103 o expansiune important\u0103 a rezervei de celule T CD4+ \u015fi celule T CD8+ specifice antigenului patogen. Numeroase studii demonstreaz\u0103 faptul c\u0103 m\u0103rimea rezervei de celule T de memorie depinde de m\u0103rimea \u201eexploziei\u201d de celule T antigen specifice din timpul fazei de expansiune. Celulele T de memorie pot fi clasificate \u00een: celule T centrale de memorie \u015fi celule T efectoare de memorie.<\/span><\/p>\n

Trebuie re\u0163inut c\u0103 celulele T de memorie pot prolifera \u015fi produce citokine ca r\u0103spuns la o stimulare cu o cantitate mai mic\u0103 de antigen, cu o costimulare mai slab\u0103 \u015fi mult mai rapid comparativ cu celulele T naive. In plus, ele pot promova \u015fi intensifica func\u0163ia APC \u015fi accelera activitatea celulelor T naive.<\/span><\/p>\n

\u00cen absen\u0163a stimul\u0103rii antigenice, celule T de memorie pot suferi o proliferare homeostatic\u0103 pentru a-\u015fi reface rezerva. Celulele T de memorie CD4+ \u015fi CD8+ \u00ee\u015fi pot p\u0103stra responsivitatea lor rapid\u0103\u00a0\u00een absen\u0163a stimulului antigenic \u015fi sunt capabile s\u0103 confere o imunitate protectiv\u010311;12<\/sup>.<\/span><\/p>\n\n\n\n\n\n\n\n
MARKER<\/span><\/td>\nCelule T naive<\/span><\/td>\nCelule T efectoare<\/span><\/td>\nCelule T de memorie<\/span><\/td>\n<\/tr>\n
CD62L<\/span><\/td>\n\u0417<\/span><\/td>\n\u041c<\/span><\/td>\nH\/L<\/span><\/td>\n<\/tr>\n
CCR7<\/span><\/td>\n\u0417<\/span><\/td>\n\u041c<\/span><\/td>\nH\/L<\/span><\/td>\n<\/tr>\n
CD45RA<\/span><\/td>\n\u0417<\/span><\/td>\n\u041c<\/span><\/td>\nH\/L<\/span><\/td>\n<\/tr>\n
CD45RO<\/span><\/td>\n\u041c<\/span><\/td>\n\u0417<\/span><\/td>\nL\/H<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Tabel 17.9.1.3\u00a0 Markeri pentru diferen\u0163ierea celulelor T<\/span><\/em><\/p>\n

H = exprimare marcat\u0103; L= exprimare slab\u0103\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/span><\/p>\n

Profilul imun de baz\u0103 \u015fi recomand\u0103ri pentru efectuarea acestui test<\/span><\/strong><\/em><\/p>\n

\u00cen cadrul profilului de baz\u0103 sunt determinate at\u00e2t procentual c\u00e2t \u015fi \u00een valoare absolut\u0103 principalele subseturi de limfocite implicate \u00een r\u0103spunsul imun, prin identificarea markerilor de suprafa\u0163\u0103 specifici (moleculele CD):<\/span><\/p>\n

\u2013\u00a0limfocitele totale (CD45+);<\/span><\/div>\n
\u2013 limfocitele T (CD3+);<\/span><\/div>\n
\u2013 limfocitele T helper (CD3+\/CD4+);<\/span><\/div>\n
\u2013 limfocitele T supresoare\/citotoxice (CD3+\/CD8+);<\/span><\/div>\n
\u2013 raportul CD4+\/CD8+;<\/span><\/div>\n
\u2013 limfocitele T imature CD3+\/CD8+\/CD4+\u00a0;<\/span><\/div>\n
\u2013 limfocitele B (CD19+);<\/span><\/div>\n
\u2013 celulele NK (CD3-\/CD16+\/CD56+).<\/span><\/div>\n

Principala aplica\u0163ie a determin\u0103rii subclaselor limfocitare este screening-ul, evaluarea \u015fi monitorizarea deficien\u0163elor imune, caracterizate prin infec\u0163ii recurente, unele amenin\u0163\u0103toare de via\u0163\u0103, ce pot fi bacteriene, virale \u015fi\/sau fungice \u00een func\u0163ie de natura deficien\u0163ei. <\/span><\/span><\/p>\n

Imunodeficien\u0163ele primare (congenitale) sunt afec\u0163iuni rar \u00eent\u00e2lnite, cu o frecven\u0163\u0103 estimat\u0103 la 1\/10000 na\u015fteri vii, \u00een schimb mult mai frecvente sunt imunodeficien\u0163ele secundare din boli maligne limfo-reticulare, boli autoimune, tratamente imunosupresoare, infec\u0163ii virale, deficien\u0163e nutri\u0163ionale, boli cu pierdere de proteine.<\/span><\/span><\/p>\n

Deficien\u0163ele imune celulare pot fi numerice sau func\u0163ionale, put\u00e2nd fi implicate neutrofilele sau limfocitele. Pe baza hemogramei poate fi depistat un num\u0103r sc\u0103zut al uneia din clasele de leucocite, \u00eens\u0103 num\u0103rul total de limfocite este inadecvat pentru investigarea unei deficien\u0163e imune, fiind necesar\u0103 cuantificarea separat\u0103 a principalelor subseturi limfocitare B, T si NK prin citometrie \u00een flux. <\/span><\/span><\/p>\n

Pentru identificarea deficitelor imune celulare func\u0163ionale sunt disponibile teste func\u0163ionale. <\/span><\/span><\/p>\n

Sunt descrise peste 200 tipuri de imunodeficien\u0163e primare, aproximativ 170 dintre ele av\u00e2nd defecte genetice identificate. Heterogenitatea clinic\u0103 \u015fi imunologic\u0103 a acestor afec\u0163iuni face ca diagnosticul s\u0103 fie dificil, necesit\u00e2nd corelarea datelor clinice \u015fi radiologice cu teste imunologice \u015fi genetice. <\/span><\/span><\/p>\n

Imunofenotiparea limfocitar\u0103 cu determinarea cantitativ\u0103 a subseturilor de limfocite face parte dintr-un spectru complex de teste diagnostice ce pot fi efectuate prin citometrie \u00een flux, cum ar fi identificarea unor proteine anormale specifice unei anumite boli, precum \u015fi teste func\u0163ionale, acestea constituind \u00een general apanajul unor laboratoare specializate. <\/span><\/span><\/p>\n

Informa\u0163iile ob\u0163inute pe baza imunofenotip\u0103rii, \u00een corela\u0163ie cu alte date clinice \u015fi de laborator, permit selec\u0163ia testelor ulterioare necesare pentru diagnosticul de certitudine, \u00een special teste genetice. <\/span><\/span><\/p>\n

\u00a0<\/span>\u2013 Imunodeficien\u0163a comun\u0103 variabil\u0103 (CVID) include un grup heterogen de boli, av\u00e2nd prevalen\u0163a cea mai mare \u00eentre imunodeficien\u0163ele primare. CVID se caracterizeaz\u0103 prin anomalii ale limfocitelor B, au prezentare bimodal\u0103, \u00een copil\u0103ria timpurie, respectiv \u00eentre 15-40 ani, 4 muta\u0163ii genetice diferite fiind asociate cu aceasta. Pacien\u0163ii se prezint\u0103 cu infec\u0163ii sino-pulmonare recurente, hipogamaglobulinemie global\u0103 \u015fi num\u0103r de limfocite B normal sau sc\u0103zut, 5-10% din pacien\u0163i prezent\u00e2nd niveluri foarte sc\u0103zute ale limfocitelor B (<1% din leucocite).<\/span><\/span><\/p>\n

Un subset de pacien\u0163i (5-10%) dezvolt\u0103 granuloame non-cazeoase sarcoid-like \u00een diferite organe \u015fi o deficien\u0163\u0103 progresiv\u0103 a limfocitelor T, \u00een unele cazuri cu num\u0103r de limfocite T CD4+ <200\/\u03bcL.<\/span><\/span><\/p>\n

Dintre to\u0163i pacien\u0163ii cu CVID, 25-30% prezint\u0103 un num\u0103r crescut de limfocite T CD8+ \u015fi raport CD4+\/CD8+ sc\u0103zut (<1).<\/span><\/span><\/p>\n

\u00a0<\/span>\u2013 Agamaglobulinemia se caracterizeaz\u0103 prin debut la v\u00e2rsta de 4-6 luni, cu infec\u0163ii sino-pulmonare \u015fi gastro-intestinale recurente, hipogamaglobulinemie global\u0103, num\u0103r foarte sc\u0103zut sau absen\u0163a limfocitelor B circulante, incapacitatea producerii de anticorpi ca r\u0103spuns la antigene, inclusiv vaccinuri, hipoplazia \u0163esuturilor limfoide secundare.<\/span><\/span><\/p>\n

\u00cen 85% din cazuri prezint\u0103 transmitere X-linkat\u0103 \u015fi se caracterizeaz\u0103 prin defecte ale expresiei Btk (Bruton`s tyrosine kinase) pe limfocite, monocite \u015fi trombocite ca urmare a unor muta\u0163ii la nivelul genei BTK.<\/span><\/span><\/p>\n

Agamaglobulinemia X-linkat\u0103 poate fi confundat\u0103 cu CVID la adul\u0163i datorit\u0103 suprapunerii principalelor caracteristici, \u00eens\u0103 numai 5% din cazurile de CVID prezint\u0103 <1% limfocite B CD19+ circulante.<\/span><\/span><\/p>\n

Confirmarea diagnosticului se bazeaz\u0103 pe evaluarea prin citometrie \u00een flux a proteinei Btk, respectiv identificarea muta\u0163iei la nivelul genei BTK.<\/span><\/span><\/p>\n

\u00a0<\/span>\u2013 Imunodeficien\u0163a sever\u0103 combinat\u0103 (SCID) este un sindrom cu poten\u0163ial letal, caracterizat prin infec\u0163ii recurente, dermatit\u0103, diaree \u015fi e\u015fecul suptului. Este cauzat de defecte moleculare numeroase, care determin\u0103 anomalii numerice \u015fi func\u0163ionale ale limfocitelor B, T \u015fi, ocazional, NK, dar \u00een majoritatea cazurilor limfocitele T sunt absente sau prezint\u0103 niveluri foarte sc\u0103zute. Pe baza unui algoritm bazat pe prezen\u0163a sau absen\u0163a limfocitelor B \u015fi NK la pacien\u0163ii cu niveluri foarte sc\u0103zute sau absen\u0163a limfocitelor T, se pot selecta testele ulterioare necesare pentru stabilirea diagnosticului. Diagnosticul corect permite instituirea promt\u0103 a tratamentului \u015fi, \u00een ultim\u0103 instan\u0163\u0103, transplantul de m\u0103duv\u0103 osoas\u0103 care asigur\u0103 supravie\u0163uirea pacientului.<\/span><\/span><\/p>\n

Un exemplu de SCID este sindromul Ommen, caracterizat prin diferen\u0163ierea par\u0163ial\u0103 a limfocitelor T datorit\u0103 unei muta\u0163ii hipomorfe la nivelul genei RAG1 (recombinase activating gene 1<\/em>) sau RAG2. La ace\u015fti pacien\u0163i, spre deosebire de pacien\u0163ii cu muta\u0163ii care determin\u0103 pierderea completa a func\u0163iei genei \u015fi la care lipsesc complet limfocitele B si T, p\u0103streaz\u0103 o activitate recombinant\u0103 V(D)J par\u0163ial\u0103 \u015fi pot genera o cantitate substan\u0163ial\u0103 de celule T oligoclonale. Totu\u015fi limfocitele B sunt complet absente \u015fi, \u00een ciuda unui nivel crescut de IgE, nu poate fi detectat un r\u0103spuns de anticorpi antigen-specifici. Clinic sindromul se caracterizeaz\u0103 prin dermatit\u0103, diaree, limfadenopatie, hepatosplenomegalie \u015fi susceptibilitate extrem\u0103 la infec\u0163ii. Pacien\u0163ii prezint\u0103 limfocitoza prin prezen\u0163a unui set de celule TH2 oligoclonale activate antigen-stimulate, precum \u015fi eozinofilie.<\/span><\/span><\/p>\n

Deficien\u0163a MHC clasa a II-a (ini\u0163ial cunoscut\u0103 ca sindromul limfocitelor goale) este o form\u0103 de SCID caracterizat\u0103 prin absen\u0163a expresiei moleculelor MHC II pe suprafa\u0163a celular\u0103, cu num\u0103r normal de limfocite B \u015fi T, dar num\u0103r sc\u0103zut de limfocite T CD4+. Pentru precizarea diagnosticului, prin citometrie \u00een flux poate fi demonstrat\u0103 absen\u0163a moleculelor MHC clasa II de pe suprafa\u0163a celulelor prezentatoare de antigen, respectiv limfocitele B sau celulele de linie monocit-macrofag.<\/span><\/span><\/p>\n

\u00a0<\/span>\u2013 Sindromul DiGeorge este o imunodeficien\u0163\u0103 primar\u0103 cu o frecven\u0163\u0103 de 1\/3000 na\u015fteri vii, caracterizat\u0103 prin hipocalcemie datorat\u0103 hipoparatiroidismului, defecte cardiace \u015fi hipoplazie sau aplazie timic\u0103. Acesta este cunoscut sub diferite nume: sindromul velo-cardio-facial, sindromul Shprintzen, CATCH 22, anomalia facial\u0103 conotruncal\u0103, toate reprezent\u00e2nd aceea\u015fi condi\u0163ie genetic\u0103, respectiv dele\u0163ia cromozomului 22q11.2, care poate avea expresie clinic\u0103 diferit\u0103. Sindromul DiGeorge \u201ccomplet\u201d cu absen\u0163a total\u0103 a timusului \u015fi imunodeficien\u0163\u0103 sever\u0103 reprezint\u0103 <0.5% din pacien\u0163i. Majoritatea pacien\u0163ilor au un defect par\u0163ial cu alterarea dezvolt\u0103rii timusului \u015fi anomalii variabile ale limfocitelor T, cu o inciden\u0163\u0103 crescut\u0103 de infec\u0163ii \u015fi boli autoimune. Imunodeficien\u0163a se datoreaz\u0103 num\u0103rului sc\u0103zut de limfocite T, al celulelor T reglatoare naturale (nTreg), \u015fi, de\u015fi num\u0103rul total de limfocite B este normal, este sc\u0103zut num\u0103rul limfocitelor B de memorie.<\/span><\/span><\/p>\n

Alte indica\u0163ii ale imofenotiparii limfocitare \u2013 profil de baz\u0103 sunt:<\/span><\/span><\/p>\n

    \n
  • Monitorizarea imun\u0103 dup\u0103 terapie imunosupresoare pentru transplant, boli autoimune, boli neoplazice.<\/span><\/span><\/li>\n
  • Utilizarea major\u0103 a imunofenotip\u0103rii \u00een transplant este reprezentat\u0103 de monitorizarea tratamentului cu globulina anti-timocitar\u0103, un nivel de celule T CD3+ de 50\/\u03bcL fiind considerat pragul pentru tratament.<\/span><\/span><\/li>\n
  • Evaluarea reconstituirii imune post-transplant de celule stem hematopoietice.<\/span><\/span><\/li>\n
  • Determinarea num\u0103rului absolut de celule B circulante la pacien\u0163ii cu leucemie limfoid\u0103 cronic\u0103, o valoare de >5\u00d7109<\/sup>\/L fiind necesar\u0103 pentru diagnosticul de LLC conform ghidurilor 2008 pentru diagnostic \u015fi tratament \u00een LLC.<\/span><\/span><\/li>\n<\/ul>\n

    Specimen recoltat<\/strong> \u2013 s\u00e2nge venos5<\/sup>.\u00a0<\/span><\/p>\n

    Recipient de recoltare<\/strong> \u2013 vacutainer ce con\u0163ine EDTA ca anticoagulant5<\/sup>.<\/span><\/p>\n

    Volum prob\u0103<\/strong> \u2013 5 mL s\u00e2nge3<\/sup>.<\/span><\/p>\n

    Stabilitate prob\u0103<\/strong> \u2013 s\u00e2ngele trebuie s\u0103 ajung\u0103 \u00een maxim 24 ore la laboratorul la care se efectueaz\u0103 testul \u015fi \u00een aceast\u0103 perioad\u0103 se p\u0103streaz\u0103 la temperatura camerei. Este contraindicat\u0103 refrigerarea probei<\/span>5<\/sup>.<\/span><\/p>\n

    Cauze de respingere a probei<\/strong> \u2013 specimene care au dep\u0103\u015fit intervalul de stabilitate, probe refrigerate sau congelate5<\/sup>.<\/span><\/p>\n

    Metod\u0103<\/strong> - citometrie \u00een flux<\/span>5<\/sup>.<\/span><\/p>\n

    Valori de referin\u0163\u0103 \u015fi comunicarea rezultatelor<\/span><\/em><\/strong><\/p>\n

    Buletinul final va con\u0163ine intervalele de referin\u0163\u0103 pentru subseturile limfocitare adecvate v\u00e2rstei pacientului \u00eempreun\u0103 cu o interpretare a rezultatelor ob\u0163inute5<\/sup>.<\/span><\/p>\n

    Trebuie cunoscut faptul c\u0103 num\u0103rul absolut al popula\u0163iilor limfocitare este influen\u0163at de o serie de factori biologici, inclusiv hormoni, temperatur\u0103 \u015fi mediul \u00eenconjur\u0103tor. Studiile legate de varia\u0163iile circadiane au demonstrat o cre\u015ftere progresiv\u0103 a num\u0103rului de celule CD4+ \u00een cursul zilei, \u00een timp ce limfocitele CD8+ \u015fi limfocitele B CD19+ cresc doar \u00een prima parte a zilei, f\u0103r\u0103 a se modifica \u00een cursul dup\u0103-amiezei. Din acest motiv, atunci c\u00e2nd se efectueaz\u0103 o monitorizare seriat\u0103 a popula\u0163iilor limfocitare se recomand\u0103 ca probele de s\u00e2nge s\u0103 se recolteze \u00een acela\u015fi moment al zilei8<\/sup>.<\/span><\/p>\n

    \u00a0<\/span><\/p>\n

    \u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f:<\/strong><\/span><\/p>\n

    1. ARUP Laboratories. Test Directory: Lymphocyte Subset Panel 5 \u2013 Total Lymphocyte Enumeration. www.aruplab.com 2010. Ref Type: Internet Communication.<\/span><\/div>\n
    2. Christopher S. Baliga, Mary E. Paul, Javier Chinen, William T. Shearer. HIV Infection and Acquired Immunodeficiency Syndrome. In Clinical Immunology. Principles and Practice, Mosby, Elsevier, Third Edition, 2008, 571-582.<\/span><\/div>\n
    3. Kenneth Todar. Immune Defense against Bacterial Pathogens: Adaptive or Acquired Immunity. In Todar\u2019s Online Textbook of Bacteriology. www.textbookofbacteriology.net\/adaptive. Reference Type: Internet Communication.<\/span><\/div>\n
    4. Kimberley W. Sanford, Susan D. Roseff. Immunodeficiency Disorders. In Henry\u2019s Clinical Diagnosis and Management by Laboratory Methods- Sauders Elsevier 21-Ed 2007, 906-913.<\/span><\/div>\n
    5. Laborator Synevo. Referin\u0163ele specifice tehnologiei de lucru utilizate 2010. Ref Type: Catalog.<\/span><\/div>\n
    6. Laboratory Corporation of America. Directory of Services and Interpretive Guide. T- and B-Lymphocyte Differential Profile. www.labcorp.com 2010. Ref Type: Internet Communication<\/span><\/div>\n
    7. Marie-Dominique Franco. Immunology, HIV and AIDS. http:\/\/www.biol.sc.edu\/courses. Ref Type: Internet Communication.<\/span><\/div>\n
    8. Mayo Clinic\/Mayo Medical Laboratories. Test Catalog. T- and B-Cell Quantitation by Flow Cytometry. www.mayomedicallaboratories.com. Ref Type: Internet Communication<\/span><\/div>\n
    9. Paul A. Linnemeyer. The Immune System \u2013 An Overview, 2008. www.the body.com. Ref Type: Internet Communication.<\/span><\/div>\n
    10. Prof. Schlissel. The Immunology of HIV Infection and AIDS. http:\/\/mcb.berkeley.edu\/courses. Ref Type: Internet Communication.<\/span><\/div>\n
    11. Robert R. Rich, Thomas A. Fleisher. William T. Shearer, Harry W. Schroeder, Anthony J. Frew, Cornelia M. Weyand. Fundamental Principles of the Immune Response. In Clinical Immunology. Principles and Practice, Mosby, Elsevier, Third Edition, 2008, 3-127.<\/span><\/div>\n
    12. Shane Crotty, Rafi Ahmed. Immunological Memory. In Topley & Wilson Microbiology & Microbial Infections, Immunology, Hodder Arnold, 10th Edition, 2005, 487-503.<\/span><\/div>","protected":false},"excerpt":{"rendered":"

    \u041e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u0435 \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u043e\u0433\u043e \u0441\u043e\u0441\u0442\u0430\u0432\u0430 (\u0438\u043c\u043c\u0443\u043d\u043e\u0444\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435) \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432 \u043a\u0440\u043e\u0432\u0438 \u2013 \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u0439 \u043a\u043e\u043c\u043f\u043e\u043d\u0435\u043d\u0442 \u0432 \u043e\u0446\u0435\u043d\u043a\u0435 \u0438\u043c\u043c\u0443\u043d\u043d\u043e\u0433\u043e \u0441\u0442\u0430\u0442\u0443\u0441\u0430 \u2013 \u0432\u044b\u043f\u043e\u043b\u043d\u044f\u0435\u0442\u0441\u044f \u043c\u0435\u0442\u043e\u0434\u043e\u043c \u043f\u0440\u043e\u0442\u043e\u0447\u043d\u043e\u0439 \u0446\u0438\u0442\u043e\u0444\u043b\u044e\u043e\u0440\u0438\u043c\u0435\u0442\u0440\u0438\u0438.<\/p>\n

    \u0418\u043c\u043c\u0443\u043d\u043e\u0444\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 \u2013 \u044d\u0442\u043e \u0445\u0430\u0440\u0430\u043a\u0442\u0435\u0440\u0438\u0441\u0442\u0438\u043a\u0430 \u043a\u043b\u0435\u0442\u043e\u043a, \u043f\u043e\u043b\u0443\u0447\u0435\u043d\u043d\u0430\u044f \u043f\u0440\u0438 \u043f\u043e\u043c\u043e\u0449\u0438 \u043c\u043e\u043d\u043e\u043a\u043b\u043e\u043d\u0430\u043b\u044c\u043d\u044b\u0445 \u0430\u043d\u0442\u0438\u0442\u0435\u043b \u0438\u043b\u0438 \u043a\u0430\u043a\u0438\u0445-\u043b\u0438\u0431\u043e \u0434\u0440\u0443\u0433\u0438\u0445 \u0437\u043e\u043d\u0434\u043e\u0432, \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u044e\u0449\u0438\u0445 \u0441\u0443\u0434\u0438\u0442\u044c \u043e\u0431 \u0438\u0445 \u0442\u0438\u043f\u0435 \u0438 \u0444\u0443\u043d\u043a\u0446\u0438\u043e\u043d\u0430\u043b\u044c\u043d\u043e\u043c \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u0438 \u043f\u043e \u043d\u0430\u043b\u0438\u0447\u0438\u044e \u0442\u043e\u0433\u043e \u0438\u043b\u0438 \u0438\u043d\u043e\u0433\u043e \u043d\u0430\u0431\u043e\u0440\u0430 \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u044b\u0445 \u043c\u0430\u0440\u043a\u0435\u0440\u043e\u0432.<\/p>\n

    \u0418\u043c\u043c\u0443\u043d\u043e\u0444\u0435\u043d\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435\u00a0\u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u043e\u0432\u00a0\u0437\u0430\u043a\u043b\u044e\u0447\u0430\u0435\u0442\u0441\u044f \u0432 \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0435\u043d\u0438\u0438 \u043d\u0430 \u0438\u0445 \u043f\u043e\u0432\u0435\u0440\u0445\u043d\u043e\u0441\u0442\u0438 \u043c\u0430\u0440\u043a\u0435\u0440\u043e\u0432 \u0434\u0438\u0444\u0444\u0435\u0440\u0435\u043d\u0446\u0438\u0430\u0446\u0438\u0438, \u0438\u043b\u0438 CD-\u0430\u043d\u0442\u0438\u0433\u0435\u043d\u043e\u0432. \u041b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u044b \u044d\u043a\u0441\u043f\u0440\u0435\u0441\u0441\u0438\u0440\u0443\u044e\u0442 \u0440\u044f\u0434 \u043f\u043e\u0432\u0435\u0440\u0445\u043d\u043e\u0441\u0442\u043d\u044b\u0445 \u0438 \u0446\u0438\u0442\u043e\u043f\u043b\u0430\u0437\u043c\u0430\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0430\u043d\u0442\u0438\u0433\u0435\u043d\u043e\u0432, \u0443\u043d\u0438\u043a\u0430\u043b\u044c\u043d\u044b\u0445 \u0434\u043b\u044f \u0441\u0432\u043e\u0435\u0439 \u0441\u0443\u0431\u043f\u043e\u043f\u0443\u043b\u044f\u0446\u0438\u0438 \u0438 \u0441\u0442\u0430\u0434\u0438\u0438 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f.<\/p>\n

    CD-\u0430\u043d\u0442\u0438\u0433\u0435\u043d\u044b (\u0430\u043d\u0433\u043b. cluster of differentiation antigens) \u2013 \u044d\u0442\u043e \u0430\u043d\u0442\u0438\u0433\u0435\u043d\u044b \u043d\u0430 \u043f\u043e\u0432\u0435\u0440\u0445\u043d\u043e\u0441\u0442\u0438 \u043a\u043b\u0435\u0442\u043e\u043a, \u043c\u0430\u0440\u043a\u0435\u0440\u044b, \u043e\u0442\u043b\u0438\u0447\u0430\u044e\u0449\u0438\u0435 \u043e\u0434\u043d\u0438 \u0442\u0438\u043f\u044b \u043a\u043b\u0435\u0442\u043e\u043a \u043e\u0442 \u0434\u0440\u0443\u0433\u0438\u0445. \u0414\u0438\u0444\u0444\u0435\u0440\u0435\u043d\u0446\u0438\u0430\u0446\u0438\u0438 \u044d\u0442\u0438\u0445 \u0430\u043d\u0442\u0438\u0433\u0435\u043d\u043e\u0432 \u0438\u0437\u0443\u0447\u0435\u043d\u044b \u0438 \u0441\u0442\u0430\u043d\u0434\u0430\u0440\u0442\u0438\u0437\u043e\u0432\u0430\u043d\u044b, \u0438\u043c \u043f\u0440\u0438\u0441\u0432\u043e\u0435\u043d\u044b \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043d\u044b\u0435 \u043d\u043e\u043c\u0435\u0440\u0430. CD \u043c\u043e\u0433\u0443\u0442 \u0431\u044b\u0442\u044c \u0440\u0430\u0441\u043f\u043e\u0437\u043d\u0430\u043d\u044b \u0441 \u043f\u043e\u043c\u043e\u0449\u044c\u044e \u0441\u043e\u043e\u0442\u0432\u0435\u0442\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u0445 \u043c\u043e\u043d\u043e\u043a\u043b\u043e\u043d\u0430\u043b\u044c\u043d\u044b\u0445 \u0430\u043d\u0442\u0438\u0442\u0435\u043b. \u0418\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u044f \u0444\u043b\u044e\u043e\u0440\u0435\u0441\u0446\u0435\u043d\u0442\u043d\u043e\u043c\u0435\u0447\u0435\u043d\u044b\u0435 \u043c\u043e\u043d\u043e\u043a\u043b\u043e\u043d\u0430\u043b\u044c\u043d\u044b\u0435 \u0430\u043d\u0442\u0438\u0442\u0435\u043b\u0430, \u0441\u0432\u044f\u0437\u044b\u0432\u0430\u044e\u0449\u0438\u0435\u0441\u044f \u0441 \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043d\u044b\u043c\u0438 CD, \u043c\u043e\u0436\u043d\u043e \u0441 \u043f\u043e\u043c\u043e\u0449\u044c\u044e \u043c\u0435\u0442\u043e\u0434\u0430 \u043f\u0440\u043e\u0442\u043e\u0447\u043d\u043e\u0439 \u0446\u0438\u0442\u043e\u043c\u0435\u0442\u0440\u0438\u0438 \u0440\u0430\u0441\u0441\u0447\u0438\u0442\u0430\u0442\u044c \u0441\u043e\u0434\u0435\u0440\u0436\u0430\u043d\u0438\u0435 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432, \u043e\u0442\u043d\u043e\u0441\u044f\u0449\u0438\u0445\u0441\u044f \u043a \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u043c \u043f\u043e \u0444\u0443\u043d\u043a\u0446\u0438\u0438 \u0438\u043b\u0438 \u0441\u0442\u0430\u0434\u0438\u0438 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f \u0441\u0443\u0431\u043f\u043e\u043f\u0443\u043b\u044f\u0446\u0438\u044f\u043c.<\/p>\n

    \u0412 \u043e\u0441\u043d\u043e\u0432\u0435 \u043f\u0440\u043e\u0442\u043e\u0447\u043d\u043e\u0439 \u0446\u0438\u0442\u043e\u0444\u043b\u044e\u043e\u0440\u0438\u043c\u0435\u0442\u0440\u0438\u0438 \u043b\u0435\u0436\u0438\u0442 \u0444\u043e\u0442\u043e\u043c\u0435\u0442\u0440\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0438 \u0444\u043b\u044e\u043e\u0440\u0435\u0441\u0446\u0435\u043d\u0442\u043d\u043e\u0435 \u0438\u0437\u043c\u0435\u0440\u0435\u043d\u0438\u0435 \u043e\u0442\u0434\u0435\u043b\u044c\u043d\u044b\u0445 \u043a\u043b\u0435\u0442\u043e\u043a, \u043f\u0435\u0440\u0435\u0441\u0435\u043a\u0430\u044e\u0449\u0438\u0445 \u043e\u0434\u043d\u0430 \u0437\u0430 \u0434\u0440\u0443\u0433\u043e\u0439 \u0432\u043c\u0435\u0441\u0442\u0435 \u0441 \u043f\u043e\u0442\u043e\u043a\u043e\u043c \u0436\u0438\u0434\u043a\u043e\u0441\u0442\u0438 \u043b\u0443\u0447 \u043c\u043e\u043d\u043e\u0445\u0440\u043e\u043c\u0430\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u0441\u0432\u0435\u0442\u0430, \u043e\u0431\u044b\u0447\u043d\u043e \u0441\u0432\u0435\u0442\u0430 \u043b\u0430\u0437\u0435\u0440\u0430.<\/p>\n

    \u041c\u0435\u0442\u043e\u0434 \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u043d\u0435 \u0442\u043e\u043b\u044c\u043a\u043e \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0438\u0442\u044c \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u043e\u0435 \u0441\u043e\u043e\u0442\u043d\u043e\u0448\u0435\u043d\u0438\u0435 \u043e\u0441\u043d\u043e\u0432\u043d\u044b\u0445 \u043f\u043e\u043f\u0443\u043b\u044f\u0446\u0438\u0439 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432 \u2013<\/strong><\/p>\n

      \n
    • \u0422-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b\u00a0(<\/strong>CD<\/strong>3+<\/sup><\/strong>CD<\/strong>19–<\/sup>)<\/strong>,<\/li>\n
    • \u0422-\u0445\u0435\u043b\u043f\u0435\u0440\u044b\/\u0438\u043d\u0434\u0443\u043a\u0442\u043e\u0440\u044b\u00a0(CD3+<\/sup><\/strong>CD<\/strong>4<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
    • \u0422-\u0446\u0438\u0442\u043e\u0442\u043e\u043a\u0441\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b (\u0422-\u0426\u0422\u041b) (CD3+<\/sup><\/strong>CD<\/strong>8<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
    • \u0438\u0441\u0442\u0438\u043d\u043d\u044b\u0435 \u043d\u0430\u0442\u0443\u0440\u0430\u043b\u044c\u043d\u044b\u0435 “\u043a\u0438\u043b\u043b\u0435\u0440\u044b” (NK-\u043a\u043b\u0435\u0442\u043a\u0438)\u00a0(CD3–<\/sup><\/strong>CD<\/strong>56+<\/sup><\/strong>CD<\/strong>45<\/strong>+<\/sup>)<\/strong>,<\/li>\n
    • \u0412-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b\u00a0(CD19+<\/sup><\/strong>CD3–<\/sup>)<\/strong>, \u2013<\/strong><\/li>\n<\/ul>\n

      \u043d\u043e \u0438 \u043e\u0446\u0435\u043d\u0438\u0442\u044c \u043c\u0430\u043b\u044b\u0435 \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u044b\u0435 \u043f\u043e\u043f\u0443\u043b\u044f\u0446\u0438\u0438, \u0430 \u0442\u0430\u043a\u0436\u0435 \u0438\u0437\u0443\u0447\u0438\u0442\u044c \u0438\u0445 \u0444\u0443\u043d\u043a\u0446\u0438\u043e\u043d\u0430\u043b\u044c\u043d\u0443\u044e \u0430\u043a\u0442\u0438\u0432\u043d\u043e\u0441\u0442\u044c:<\/strong><\/p>\n

        \n
      • \u0422-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b, \u044d\u043a\u0441\u043f\u0440\u0435\u0441\u0441\u0438\u0440\u0443\u044e\u0449\u0438\u0435 \u043c\u0430\u0440\u043a\u0435\u0440\u044b NK-\u043a\u043b\u0435\u0442\u043e\u043a (\u0422-NK-\u043a\u043b\u0435\u0442\u043a\u0438) (CD3+<\/sup><\/strong>CD16+<\/sup><\/strong>56+<\/sup><\/strong>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
      • NK-\u043a\u043b\u0435\u0442\u043a\u0438 \u0446\u0438\u0442\u043e\u043b\u0438\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 (CD3–<\/sup><\/strong>CD<\/strong>16+(<\/sup><\/strong>or<\/sup><\/strong>high<\/sup><\/strong>)\u00a0<\/sup><\/strong>CD<\/strong>56<\/strong>dim<\/sup><\/strong>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
      • NK-\u043a\u043b\u0435\u0442\u043a\u0438 \u0446\u0438\u0442\u043e\u043a\u0438\u043d\u043f\u0440\u043e\u0434\u0443\u0446\u0438\u0440\u0443\u044e\u0449\u0438\u0435 (CD3–<\/sup><\/strong>CD<\/strong>16-(<\/sup><\/strong>or<\/sup><\/strong>low<\/sup><\/strong>)\u00a0<\/sup><\/strong>CD<\/strong>56<\/strong>bright<\/sup><\/strong>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
      • NK-\u043a\u043b\u0435\u0442\u043a\u0438, \u044d\u043a\u0441\u043f\u0440\u0435\u0441\u0441\u0438\u0440\u0443\u044e\u0449\u0438\u0435 \u0430\u043b\u044c\u0444\u0430-\u0446\u0435\u043f\u044c \u0430\u043d\u0442\u0438\u0433\u0435\u043d\u0430 CD8\u00a0(CD3–<\/sup>\u0421<\/strong>\u0413<\/strong>8<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/strong><\/li>\n
      • \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u044b\u0435 \u0412-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b\u00a0(CD3–<\/sup><\/strong>CD<\/strong>25<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
      • \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u044b\u0435 \u0422-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b\u00a0(CD3+<\/sup><\/strong>HLA<\/strong>–<\/strong>DR<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>) \u0438 \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u044b\u0435 \u0446\u0438\u0442\u043e\u0442\u043e\u043a\u0441\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b\u00a0(CD8+<\/sup><\/strong>HLA<\/strong>–<\/strong>DR<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/li>\n
      • \u0412-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b \u0438 \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u044b\u0435 NK-\u043a\u043b\u0435\u0442\u043a\u0438\u00a0(CD3–<\/sup><\/strong>HLA<\/strong>–<\/strong>DR<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>)<\/strong>,<\/li>\n
      • \u0430\u043a\u0442\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u043d\u044b\u0435 \u0422-\u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u044b, \u044d\u043a\u0441\u043f\u0440\u0435\u0441\u0441\u0438\u0440\u0443\u044e\u0449\u0438\u0435 \u0430\u043b\u044c\u0444\u0430-\u0446\u0435\u043f\u044c \u0440\u0435\u0446\u0435\u043f\u0442\u043e\u0440\u0430 \u0418\u041b-2\u00a0(CD3+<\/sup><\/strong>CD<\/strong>25<\/strong>+<\/sup>CD<\/strong>45<\/strong>+<\/sup>),<\/strong><\/li>\n
      • \u0440\u0435\u0433\u0443\u043b\u044f\u0442\u043e\u0440\u043d\u044b\u0435 \u0422-\u0445\u0435\u043b\u043f\u0435\u0440\u043d\u044b\u0435 \u043a\u043b\u0435\u0442\u043a\u0438\u00a0(<\/strong>CD<\/strong>4+<\/sup><\/strong>CD<\/strong>25<\/strong>bright<\/sup><\/strong>CD<\/strong>127<\/strong>neg<\/sup><\/strong>CD<\/strong>45+<\/sup>),<\/strong>\u00a0\u0432\u044b\u043f\u043e\u043b\u043d\u044f\u044e\u0449\u0438\u0435 \u0438\u043c\u043c\u0443\u043d\u043e\u0441\u0443\u043f\u0440\u0435\u0441\u0441\u043e\u0440\u043d\u0443\u044e \u0444\u0443\u043d\u043a\u0446\u0438\u044e.<\/li>\n<\/ul>\n

        \u0422\u0430\u043a\u043e\u0435 \u0432\u0441\u0435\u0441\u0442\u043e\u0440\u043e\u043d\u043d\u0435\u0435 \u0438\u0437\u0443\u0447\u0435\u043d\u0438\u0435 \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u043e\u0433\u043e \u0441\u043e\u0441\u0442\u0430\u0432\u0430 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432\u00a0\u0432 \u0441\u043e\u0432\u043e\u043a\u0443\u043f\u043d\u043e\u0441\u0442\u0438 \u0441 \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u0430\u043c\u0438 \u0434\u0440\u0443\u0433\u0438\u0445 \u0442\u0435\u0441\u0442\u043e\u0432, \u0432\u0445\u043e\u0434\u044f\u0449\u0438\u0445 \u0432 \u0441\u043e\u0441\u0442\u0430\u0432 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f, \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u0443\u0441\u0442\u0430\u043d\u043e\u0432\u0438\u0442\u044c \u0431\u043e\u043b\u0435\u0435 \u0442\u043e\u043d\u043a\u0438\u0435 \u043c\u0435\u0445\u0430\u043d\u0438\u0437\u043c\u044b \u0438\u043c\u043c\u0443\u043d\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0439. \u041e\u043d\u0438 \u043f\u0440\u043e\u00ad\u0432\u043e\u0434\u044f\u0442\u0441\u044f \u0434\u043b\u044f \u0443\u0442\u043e\u0447\u043d\u0435\u043d\u0438\u044f \u0441\u0442\u0435\u043f\u0435\u043d\u0438 \u0438 \u0433\u043b\u0443\u0431\u0438\u043d\u044b \u043f\u043e\u0440\u0430\u0436\u0435\u043d\u0438\u044f \u0438\u043c\u043c\u0443\u043d\u043d\u043e\u0439 \u0441\u0438\u0441\u0442\u0435\u043c\u044b \u0438 \u043f\u043e\u0434\u0431\u043e\u0440\u0430 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u0430 \u0434\u043b\u044f \u043f\u0440\u043e\u0432\u0435\u0434\u0435\u043d\u0438\u044f \u043f\u043e\u0441\u043b\u0435\u0434\u0443\u044e\u0449\u0435\u0439 \u0430\u0434\u0435\u043a\u00ad\u0432\u0430\u0442\u043d\u043e\u0439 \u0438\u043c\u043c\u0443\u043d\u043e\u043a\u043e\u0440\u0440\u0438\u0433\u0438\u0440\u0443\u044e\u0449\u0435\u0439 \u0442\u0435\u0440\u0430\u043f\u0438\u0438, \u043e\u0446\u0435\u043d\u043a\u0438 \u044d\u0444\u0444\u0435\u043a\u0442\u0438\u0432\u043d\u043e\u0441\u0442\u0438 \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u043c\u043e\u0433\u043e \u043b\u0435\u0447\u0435\u043d\u0438\u044f, \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u044f \u043f\u0440\u043e\u0433\u043d\u043e\u0437\u0430 \u0442\u0435\u0447\u0435\u043d\u0438\u044f \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f.<\/p>\n

        \u041a\u043e\u0433\u0434\u0430 \u043d\u0430\u0437\u043d\u0430\u0447\u0430\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?<\/strong><\/p>\n

        \u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u0440\u0435\u043a\u043e\u043c\u0435\u043d\u0434\u043e\u0432\u0430\u043d\u043e \u0434\u043b\u044f \u043a\u043e\u043c\u043f\u043b\u0435\u043a\u0441\u043d\u043e\u0433\u043e \u043e\u0431\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u043e\u0432, \u0432\u0445\u043e\u0434\u044f\u0449\u0438\u0445 \u0432 \u0433\u0440\u0443\u043f\u043f\u0443 \u0440\u0438\u0441\u043a\u0430 \u0441\u00a0\u0438\u043d\u0444\u0435\u043a\u0446\u0438\u043e\u043d\u043d\u044b\u043c \u0438\u043c\u043c\u0443\u043d\u043e\u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u043c \u0441\u0438\u043d\u0434\u0440\u043e\u043c\u043e\u043c:<\/p>\n

          \n
        • \u0447\u0430\u0441\u0442\u044b\u0435 \u041e\u0420\u0412\u0418, \u0445\u0440\u043e\u043d\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0438 \u041b\u041e\u0420-\u043e\u0440\u0433\u0430\u043d\u043e\u0432: \u0433\u043d\u043e\u0439\u043d\u044b\u0435 \u0441\u0438\u043d\u0443\u0441\u0438\u0442\u044b, \u043e\u0442\u0438\u0442\u044b, \u043f\u0435\u0440\u0438\u043e\u0434\u0438\u0447\u0435\u0441\u043a\u0438 \u0432\u0441\u0442\u0440\u0435\u0447\u0430\u044e\u0449\u0438\u0435\u0441\u044f \u043b\u0438\u043c\u0444\u0430\u0434\u0435\u043d\u0438\u0442\u044b, \u0432\u0438\u0440\u0443\u0441\u043d\u044b\u0435 \u043f\u043d\u0435\u0432\u043c\u043e\u043d\u0438\u0438 \u0441 \u0442\u0435\u043d\u0434\u0435\u043d\u0446\u0438\u0435\u0439 \u043a \u0440\u0435\u0446\u0438\u0434\u0438\u0432\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u044e;<\/li>\n
        • \u0443\u0440\u043e\u0433\u0435\u043d\u0438\u0442\u0430\u043b\u044c\u043d\u044b\u0435 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0438;<\/li>\n
        • \u0440\u0435\u0446\u0438\u0434\u0438\u0432\u0438\u0440\u0443\u044e\u0449\u0438\u0439 \u0433\u0435\u0440\u043f\u0435\u0441 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u043e\u0439 \u043b\u043e\u043a\u0430\u043b\u0438\u0437\u0430\u0446\u0438\u0438;<\/li>\n
        • \u0433\u0430\u0441\u0442\u0440\u043e\u044d\u043d\u0442\u0435\u0440\u043e\u043f\u0430\u0442\u0438\u044f \u0441 \u0445\u0440\u043e\u043d\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u0434\u0438\u0430\u0440\u0435\u0435\u0439 \u043d\u0435\u044f\u0441\u043d\u043e\u0439 \u044d\u0442\u0438\u043e\u043b\u043e\u0433\u0438\u0438, \u0434\u0438\u0441\u0431\u0430\u043a\u0442\u0435\u0440\u0438\u043e\u0437\u043e\u043c;<\/li>\n
        • \u0434\u043b\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0439 \u0441\u0443\u0431\u0444\u0435\u0431\u0440\u0438\u043b\u0438\u0442\u0435\u0442, \u043b\u0438\u0445\u043e\u0440\u0430\u0434\u043a\u0430 \u043d\u0435\u044f\u0441\u043d\u043e\u0439 \u044d\u0442\u0438\u043e\u043b\u043e\u0433\u0438\u0438;<\/li>\n
        • \u0433\u0435\u043d\u0435\u0440\u0430\u043b\u0438\u0437\u043e\u0432\u0430\u043d\u043d\u044b\u0435 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0438: \u0441\u0435\u043f\u0441\u0438\u0441, \u0433\u043d\u043e\u0439\u043d\u044b\u0435 \u043c\u0435\u043d\u0438\u043d\u0433\u0438\u0442\u044b \u0438 \u0442.\u0434.<\/li>\n<\/ul>\n

          \u041a\u0430\u043a \u043f\u043e\u0434\u0433\u043e\u0442\u043e\u0432\u0438\u0442\u044c\u0441\u044f \u043a \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044e?<\/strong><\/p>\n

            \n
          • \u0418\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u044c \u0438\u0437 \u0440\u0430\u0446\u0438\u043e\u043d\u0430\u00a0 \u0430\u043b\u043a\u043e\u0433\u043e\u043b\u044c \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 24 \u0447\u0430\u0441\u043e\u0432 \u0434\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/li>\n
          • \u041d\u0435 \u043f\u0440\u0438\u043d\u0438\u043c\u0430\u0442\u044c \u043f\u0438\u0449\u0443 \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 12 \u0447\u0430\u0441\u043e\u0432 \u0434\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/li>\n
          • \u041f\u043e\u043b\u043d\u043e\u0441\u0442\u044c\u044e \u0438\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u044c \u043f\u0440\u0438\u0435\u043c \u043b\u0435\u043a\u0430\u0440\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432 \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 24 \u0447\u0430\u0441\u043e\u0432 \u043f\u0435\u0440\u0435\u0434 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435\u043c (\u043f\u043e \u0441\u043e\u0433\u043b\u0430\u0441\u043e\u0432\u0430\u043d\u0438\u044e \u0441 \u0432\u0440\u0430\u0447\u043e\u043c).<\/li>\n
          • \u0418\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u044c \u0444\u0438\u0437\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0438 \u044d\u043c\u043e\u0446\u0438\u043e\u043d\u0430\u043b\u044c\u043d\u043e\u0435 \u043f\u0435\u0440\u0435\u043d\u0430\u043f\u0440\u044f\u0436\u0435\u043d\u0438\u0435 \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 24 \u0447\u0430\u0441\u043e\u0432 \u0434\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/li>\n
          • \u041d\u0435 \u043a\u0443\u0440\u0438\u0442\u044c \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 30 \u043c\u0438\u043d\u0443\u0442 \u0434\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/li>\n<\/ul>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[965],"product_tag":[],"class_list":{"0":"post-10148","1":"product","2":"type-product","3":"status-publish","5":"product_cat-teste-de-imunofenotipare-limfocitara","7":"first","8":"instock","9":"sold-individually","10":"shipping-taxable","11":"purchasable","12":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/10148","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/comments?post=10148"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=10148"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=10148"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=10148"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=10148"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}