Rola limfocytów B w mechanizmach patogenezy wybranych chorób

Układ immunologiczny zdrowego człowieka ma za zadanie obronę oraz utrzymywanie homeostazy organizmu poprzez kontrolowanie antygenów zarówno wnikających do ustroju, jak i tych, które są w nim produkowane. Do najważniejszych komórek pełniących taką funkcję należą ściśle ze sobą współistniejące różne populacje limfocytów. To od nich zależą rozpoznanie antygenu i reakcja mająca na celu jego neutralizację. Jedną z form tej aktywności neutralizującej potencjalny patogen jest produkcja przeciwciał, których źródłem są limfocyty B. Zaburzenia funkcji tych tak zwanych efektorów odpowiedzi humoralnej (prowadzące w konsekwencji do zaburzeń liczby i swoistości przeciwciał) są podstawą (elementem patogenezy) wielu chorób i jako takie stały się celem licznych prac badawczych. Liczebność i proporcje klas limfocytów B, wielkość ich odpowiedzi na stymulację oraz poziom, klasy i swoistość wytwarzanych przeciwciał są bardzo ważnymi czynnikami diagnostycznymi i prognostycznymi w tak na pozór różnych chorobach, jak między innymi: przewlekła obturacyjna choroba płuc, astma oskrzelowa, śródmiąższowe zapalenie płuc, rak płuc czy, co oczywiste, liczne choroby autoimmunologiczne. Fakt ten podkreśla uniwersalność zastosowania obserwacji limfocytów B w kontroli przebiegu wielu schorzeń i ponownie wykazuje, że stan układu immunologicznego odzwierciedla stan zdrowia danej osoby. Forum Medycyny Rodzinnej 2011, tom 5, nr 1, 37-4

Hemodialysis Affects Phenotype and Proliferation of CD4-Positive T Lymphocytes

CD4+ T lymphocytes of patients with chronic kidney disease (CKD) are characterized by reduced levels of crucial surface antigens and changes in the cell cycle parameters. Recombinant human erythropoietin (rhEPO) normalizes their altered phenotype and proliferative capacity. Mechanisms leading to the deficient responses of T lymphocytes are still not clear but it is postulated that immunological changes are deepened by hemodialysis (HD). Study of activation parameters of CD4+ T lymphocytes in hemodialyzed and predialysis CKD patients could bring insight into this problem. Two groups of patients, treated conservatively (predialysis, PD) and hemodialyzed (HD), as well as healthy controls, were included into the study; neither had received rhEPO. Proportions of main CD4+CD28+, CD4+CD25+, CD4+CD69+, CD4+CD95+, and CD4+HLA-DR+ lymphocyte subpopulations and proliferation kinetic parameters were measured with flow cytometry, both ex vivo and in vitro. No differences were seen in the proportions of main CD4+ lymphocyte subpopulations (CD4+CD28+, CD4+CD25+, CD4+HLA-DR+, CD4+CD69+, CD4+CD95+) between all examined groups ex vivo. CD4+ T lymphocytes of HD patients exhibited significantly decreased expression of co-stimulatory molecule CD28 and activation markers CD25 and CD69 after stimulation in vitro when compared with PD patients and healthy controls. HD patients showed also decreased percentage of CD4+CD28+ lymphocytes proliferating in vitro; these cells presented decreased numbers of finished divisions after 72 h of stimulation in vitro and had longer G0→G1 time when compared to healthy controls. CD4+ T lymphocytes of PD patients and healthy controls were characterized by similar cell cycle parameters. Our study shows that repeated hemodialysis procedure influences phenotype and proliferation parameters of CD4+ T lymphocytes

Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor circinelloides in Innate Granulomas In Vivo

Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modeled by a combined in silico modeling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo. In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo. Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients