Imunopatologia infecției tuberculoase

In anul 1905 Robert Koch primea Premiul Nobel pentru rezultatele obtinute in domeniul cercetarii infectiei tuberculoase dupa ce, in urma cu 23 de ani, reusise sa atraga atentia lumii medicale anuntind izolarea pentru prima data a agentului etiologic al tuberculozei umane si bovine si descriind metodele de coloratie utilizate pentru evidentierea bacteriei intracelulare, tehnica de cultivare si rezultatele inocularii bacilului la animale (1).

In ciuda faptului ca este o afectiune cunoscuta de multa vreme, tuberculoza ramine si in prezent o problema majora de sanatate publica. Previziumile optimiste din anul 1970, conform carora prin cresterea nivelului de trai tuberculoza va deveni o boala a trecutului, au fost infirmate de datele statistice ale anilor ce au urmat. In anul 1993 Organizatia Mondiala a Sanatatii (OMS) declara tuberculoza urgenta sanitara pe plan mondial in conditiile in care anual se inregistreaza aproximativ 7 milioane de cazuri noi si 1,5 milioane de decese cauzate de aceasta afectiune (6,2). Pentru anul 2015 este prevazuta o crestere a numarului cazurilor de tuberculoza pina la 10 milioane, tendinta de crestere mentinindu-se si in ceea ce priveste numarul deceselor cauzate de aceasta afectiune (26). Cresterea semnificativa a incidentei in ultimii ani este cauzata si de infectia cu virusul imunodeficientei umane (HIV)/SIDA care scade capacitatea de aparare a organismului si amplifica, de aproximativ 30 de ori, riscul imbolnavirii in urma contactului cu Mycobacterium tuberculosis.

Tuberculoza umana este cauzata de Mycobacterium tuberculosis (M. tuberculosis), bacterie ce apartine genului Mycobacterium din care fac parte mai mult de 50 de specii si care se caracterizeaza prin acidorezistenta, structura chimica a acizilor micolici si prin stuctura antigenica.

Din grupul Mycobacterium tuberculosis fac parte patru specii micobacteriene cu crestere lenta : M. tuberculosis- agentul etiologic al tuberculozei umane, M. bovis- bacilul tuberculozei bovine, M. microti si M. africanum. M. tuberculosis face parte din grupul bacteriilor cu dezvoltare facultativ intracelulara si "in vivo" se localizeaza exclusiv in interiorul macrofagelor (Mf) organismului gazda.

II. M. tuberculosis - structura antigenica

Antigenele micobacteriene sunt utilizate frecvent pentru clasificarea, identificarea si tiparea micobacteriana, iar in ceea ce priveste M. tuberculosis multe dintre cercetari sunt orientate spre identificarea structurilor antigenice generatoare de memorie imunologica antituberculoasa in vederea obtinerii de noi vaccinuri cu eficienta superiora vaccinului BCG utilizat in prezent.

Studiile efectuate de Robert Koch pe antigenele M. tuberculosis obtinute din filtratul culturilor de scurta durata au reprezentat inceputurile unor cercetari ample, care dureaza si in prezent si care incearca definirea precum si caracterizarea antigenelor micobacteriene.

Tuberculinele

Primele extracte micobacteriene folosite experimental au fost tuberculinele obtinute de R. Koch. Initial a fost utilizat "Old Tuberculin ", un preparat obtinut prin cultivarea M. tuberculosis timp de citeva saptamini, filtrarea mediului de cultura si concentrarea acestuia prin evaporare, iar apoi "New Tuberculin ", un preparat micobacterian obtinut prin uscare in vid si resuspensionarea bacililor tuberculosi in mixtura de apa cu glicerol. Aparitia unor reactii nespecifice, cauzate de constituentii mediului de cultura, a impus separarea antigenelor micobacteriene de impuritatile existente in "tuberculina veche" rezultind astfel "Purified Protein Derivative" (PPD), produs utilizat si astazi pe scara larga in testele cutanate de determinare a raspunsului imun celular fata de antigenele micobacteriane (3).

Chiar daca PPD este departe de a fi preparatul ideal din cauza degradarii antigenelor (mai ales a celor cu specificitate de specie), urmare a proceselor de autoliza, incalzire si precipitare proteica, incercarile ulterioare de a imbunatati calitatea preparatului PPD prin izolarea antigenelor individuale nu au dus insa la obtinerea unui produs cu eficienta si relevanta clinica superioare.

Antigenele micobacteriene se clasifica in functie de mai multe criterii:

- in functie de localizarea lor antigenele se impart in citoplasmatice (solubile) si antigene ale peretelui celular (insolubile) ;

- in functie de structura chimica antigenele se clasifica in proteine si carbohidrati ;

- gradul de raspindire la speciile

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