B-cell activity in children with malaria.

BACKGROUND: Recent studies implicate deficiency of red blood cell (RBC) complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial anaemia. This study explored the involvement of B cell CD21, which has an analogous role to RBC CR1. METHODS: In a case control study conducted in Kisumu District hospital, western Kenya, children with severe malaria anaemia (SMA) and those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA for soluble CD21 (sCD21). Paired t tests were used to determine statistical significance at a = 0.05. RESULTS: Children with SMA had significantly higher lymphocyte count (9,627.7 ± 8786.1 SD vs. 5,507 ± 2436 SD, P = 0.04 in the UM group) and the computed geometric mean of mature B-cell numbers based on the absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to 2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P = 0.003). SMA group also had a higher percentage of CD20+ B cells (26.8 ± 9.7SD vs 20.9 ± 9.01 SD in the UM) (P = 0.03), indicating considerable polyclonal B-cell activation. The CD21 median flourescence intensity was lower in the SMA (246.4 ± 87.4 SD vs 369 ± 137.7 SD) (P <0.0001), probably due to complement mediated shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher levels of the complement split product C3dg (18.35 ± 10 SD vs 11.5 ± 6.8 S.D), (P = 0.0002), confirming possible role of complement in CD21 removal. Unexpectedly, the SMAs had lower levels of sCD21 (226.5 ± 131.5 SD vs 341.4 ± 137.3 SD in the UM) (P < 0.0001), indicating that the shaved CD21 is not released to peripheral circulation. CONCLUSIONS: These results implicate B-cell in pathophysiology of severe malaria that involves increased B-cell proliferation, increased complement deposition and subsequent loss of membrane-bound CD21. The loss of CD21 is not by the classical enzmatic cleavage.

Increased ratio of tumor necrosis factor-alpha to interleukin-10 production is associated with Schistosoma haematobium-induced urinary-tract morbidity.

Bladder and kidney disease, which affect approximately 25%-30% of subjects infected with Schistosoma haematobium, are mediated by T cell-dependent granulomatous responses to schistosome eggs. To determine why only some infected subjects develop disease, we examined the hypothesis that infected Kenyan subjects with ultrasound-detected urinary-tract morbidity (n=49) had dysregulated cytokine production leading to enhanced granulomatous responses, compared with subjects of similar age and intensity of infection without morbidity (n=100). Peripheral blood mononuclear cells from subjects with morbidity produced 8-fold greater levels of egg antigen-driven tumor necrosis factor (TNF)-alpha and had a 99-fold greater mean TNF-alpha:interleukin (IL)-10 ratio, compared with subjects without disease. No differences in cytokine response to non-egg-derived schistosome antigens were observed between groups. Subjects with morbidity had increased TNF-alpha production in response to endotoxin, suggesting an innate hyperresponsiveness. These results indicate that increased TNF-alpha production, relative to that of IL-10, is associated with developing bladder-wall morbidity with S. haematobium infection.

Cellular immunity to Echinococcus granulosus cysts.

A fundamental feature of Echinococcus granulosus infection is its chronicity. There are many reasons for this, including weak natural immunity and the ability of the larval stages to evade or resist elimination by the hosts' specific immune responses. To identify the types of hosts' cellular immune response, a series of ultrastructral studies of hydatid cysts surgically removed from Turkana patients was conducted based on transmission electron microscopy. Ultrastructurally, the ectocyst (adventitial layer) is organised into three layers; an inner layer containing mainly the infiltrating mononuclear leukocytes; a middle, loose connective tissue layer with inflammatory cells mainly plasma cells, fibroblasts, scant neutrophils, eosinophils and lymphocytes, and an outer loose connective tissue layer that blends with the surrounding host tissue. The mast cells and basophils were not observed. This study has showm that the adventitial layer of hydatid cysts infiltrated by leukocytes, principally by macrophages and plasma cells.

Echinococcus granulosus: ultrastructural effect of albendazole therapy.

The effects of the anthelmintic Albendazole against Echinococcus granulosus hydatid cysts in Turkana patients given orally were studied by means of ultrasound as well as light microscopy, scanning and transmission electron microscopy. The treatment generally reduced the size of the cyst mass, making the patients feel well. The drug therapy caused collapse of the cyst wall and daughter cyst. The pathological changes on the germinal layer of Albendazole-treatment cysts differed widely from the untreated control hydatid tissue. The effects included morphological changes of the protoscolices, presence of lamellated bodies, necrosis with detachment of the germinal layer from the laminated layer. However, some parts of the Albendazole-treated hydatid tissue remained unaffected.