Immune Responses to Defined Plasmodium Falciparum Antigens and Disease Susceptibility in Two Subpopulations of Northern India

The aim of this study was to investigate the prevalence of naturally acquired immune response to malaria in individuals of different age groups belonging to areas of northern India, Loni PHC (LN) and Dhaulana PHC (SD) of district Ghaziabad. Plasmodium falciparum-infected erythrocyte lysate and six synthetic peptides from different stages of P. falciparum (CSP, MSP1, AMA1, RAP1, EBA175 and PfG27) were used to determine both humoral and cellular immune responses. Plasma of individual subject was also analyzed for IL-4, IL-10, IFN-γ and TNF-α level. We observed an age-wise increasing trend of immunity in these two populations. There was a significant association between the number of antibody responders and recognition of stage-specific epitopes by antibodies. Peripheral blood mononuclear cells of more than 75% of individuals proliferated in response to stimulation by all the antigens in LN area. IL-4 and IL-10 responses were significantly higher in individuals of LN Area; whereas IFN-g and   TNF-a responses were higher in individuals of SD Area. It was also noticed that the frequency of responders to stage-specific antigens was higher in individuals from the LN area where the frequency of malaria was lower. The naturally acquired immune responses to P. falciparum antigens reflected the reduced risk of malaria in the study groups. The results demonstrated immunogenicity of the epitopes to P. falciparum in population of this endemic zone

Cleavage of Kininogen and Subsequent Bradykinin Release by the Complement Component: Mannose-Binding Lectin-Associated Serine Protease (MASP)-1

Bradykinin (BK), generated from high-molecular-weight kininogen (HK) is the major mediator of swelling attacks in hereditary angioedema (HAE), a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×102 and 2.7×102 M−1s−1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients

EPR studies on Fcϒ receptor-mediated changes in lymphocyte membrane

59-61Biophysical evidence has been presented for the interaction of human lymphocyte membrane Fc receptors with aggregated IgG by severely restricting the rotational mobility of the cell surface proteins, as well as membrane lipids. Decrease in membrane fluidity was more prominent with aggregated IgG since the multivalency of Fc regions in aggregated IgG cross-linked cell surface Fc receptor