Comparison of immune activation in normal brain (a) versus HD brain (b). The normal brain is in a state wherein the microglia cells are in a resting state and are surveying its microenvironment. The BBB protects the brain from circulating immune cells such as DCs as well as pathogens and other foreign material. However, in the HD brain, the damaged neuron has aggregated mHtt and this activates the resting microglia cells and hence leads to phagocytosis of the cell debris along with secretion of proinflammatory cytokines that leads to neuroinflammation. This neuroinflammation weakens the BBB leading to infiltration of DCs and further elicits the immune response. Microglia cells that express mHtt also contribute to the inflammation and degeneration of the brain cells.
