Saturday, February 23, 2019

Basic components of the immune system part 158




Focusing more closely on the type of DC (Dendritic cells) needed to achieve its vaccine potential, the subsets of DCs could prove critical. Much of the current research is being carried out with monocyte-derived DCs, which are potent and homogenous  stimulators of immunity. Monocyte-derived DCs can be readily generated within a few days in large numbers (300million-500million mature DCs per apheresis) from precursors in the blood without the need for pretreating in patients with various cytokines such as GM-CSF or FLT 3-L. Rather, one obtains population of immature DCs by exposing monocyte to GM-CSF and IL-4, and then they are differentiated into mature DCs by various stimuli  such as toll-like receptor (TLR) ligands (LPS or poly I:C), inflammatory cytokines (IL-1β, TNF-α, IL-6 and PGE2), or CD40L. The use of DCs that have received a maturation stimulus is likely to be important to induce strong immunity. It has become clear that antigen delivered on immature or incompletely mature d DCs can even induce tolerance. However, the type and the duration of the maturation stimulus remain to be determined and may influence efficacy. At this time, monocyte derived DCs are the most accessible and homogenous population of DCs.

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