Damaged cells activate the immune system
Cells continuously die in our bodies from injury, infection or age. To maintain healthy tissues, dead or dying cells are cleared from the body by special cells called phagocytes. These surround and enclose the cell remains within a bubble of fats called a vesicle, then release chemicals to digest them into small, harmless pieces. Whether the engulfed cell activates the immune system depends on the type of phagocyte and the nature of the cell remains. Dendritic cells, for example, are specialised phagocytes that trigger an appropriate immune response upon recognising harmful or abnormal cells like pathogenic bacteria or tumours. The DNGR-1 IN DCS (The dendritic cell receptor DNGR-1: Modulation of endosomal dynamics upon recognition of necrotic cells) project wanted to find out how dendritic cells control the immune system’s response to damaged cells. Scientists already know that after recognising and engulfing a harmful cell, dendritic cells bring pieces of the cell’s proteins, known as antigens, to their surface. They then present these antigens to specialised immune cells called killer T-cells, each containing a unique receptor that binds to a matching antigen. Once the antigen is bound to the T-cell receptor, the killer T-cell forevermore destroys any cells containing that specific antigen. Project researchers found that a receptor called DNGR-1 on dendritic cell surfaces controls whether antigens are presented to killer T-cells or not. When DNGR-1 recognises a pathogen or damaged cell, it binds to the cell and is engulfed within the phagocyte along with its target. DNGR-1 then delays formation of the vesicle that usually degrades the contents of the engulfed cell. In doing so, DNGR-1 ensures that the cell’s antigens remain intact long enough to be presented to killer T-cells, prolonging the immune response. By understanding how DNGR-1 works, scientists can design artificial antigens that bind to the DNGR-1 receptor to be presented to killer T-cells. This approach can be used to target both pathogens and tumour cells in vaccination and immunotherapy strategies.
Keywords
Damaged cells, immune system, phagocytes, antigens, killer T-cells
