We recently observed immunostimulatory properties in the root extracts of chemotypes NMITLI-101,
NMITLI-118, NMITLI-128 and pure withanolide, Withaferin A. In the present study, we evaluated the potential immunoprophylactic efficacies of these extracts against an infective pathogen. Our results show that administration of aqueous ethanol extracts (10 mg/kg) and Withaferin A (0.3 mg/kg), 7 days before and after challenge with human filarial parasite Brugia malayi offer differential protection in Mastomys coucha with chemotype 101R offering best protection (53.57%) as compared to other chemotypes. Our findings also demonstrate that establishment of B .malayi larvae was adversely affected by pre-treatment with Withaferin A as evidenced Selleck Selumetinib by 63.6% reduction in adult
worm establishment. Moreover, a large percentage of the established female worms (66.2%) also showed defective embryogenesis. While the filaria-specific immunological response induced by Withaferin A and NMITLI-101 showed a mixed Th1/Th2 phenotype, 118R stimulated production of IFN-γ, and 128R increased levels of IL-4. Taken together, our findings reveal potential immunoprophylactic properties of Withania somnifera and further studies are needed to ascertain the benefits of this plant against other pathogens as well. 2011 Blackwell Publishing Ltd “
“Over the last decade, live cell imaging has revealed the surprisingly complex orchestration of antigen receptor Topoisomerase inhibitor signalling at the immunological synapse. The imaging studies showed that one of the earliest steps in antigen receptor activation Erlotinib solubility dmso is the formation of submicroscopic clusters, which regulate the early signalling events. However, the molecular mechanisms operating inside these microclusters have remained beyond the resolution of optical microscopy. Recent development of imaging techniques that approach molecular resolution in intact cells offers a first view of the molecular processes inside these structures. Here I review the contributions
of molecular imaging of the immunological synapse to our understanding of antigen receptor clustering, binding to antigens, and recruitment of signalling molecules. Finally, I provide an outlook on the future prospects of this rapidly advancing technology. Activation of antigen receptors, the T-cell receptor (TCR) and the B-cell receptor (BCR), is a highly regulated process that sets in motion the adaptive immune response. In accord with their pivotal role in immune responses, antigen receptors are tuned to an unusually high degree of ligand discrimination and sensitivity. Each lymphocyte clone responds specifically to high-affinity interactions with the cognate antigen, which potentially signifies an infection, but disregards low-affinity interactions, which occur with self structures.