Orientation of Antibody with Localized Infection and Systemic Infection
According to a study published in the Journal of Experimental Medicine on December 10th, the orientation of antibody binding to bacteria might decide the life or death to the bug. The new study is led by Pontus Nordenfelt of Harvard University and his colleagues at Lund University in Sweden. These findings may help scientists unveil why these bacteria cause millions of localized infections, but rare serious and systemic blood infections.
Make Streptococcus pyogenes as an example, which is the causative agent of strep throat, it typically invades the body's mucosal surfaces, including the throat and skin. These invasions are checked by Y-shaped immune proteins called antibodies, which attach to the bug via their arm (or "Fab", fragment antigen-binding) regions. This exposes the stalk ("Fc", fragment crystallizable) portion of the antibody, which is then recognized by immune cells, allowing them to ingest and kill the bacteria. Certain bacteria, including S. pyogenes, fight back by protein expressions on the surface that bind the Fc region of antibodies, rendering them invisible to patrolling immune cells.
Researchers suggest that the bacteria have the upper hand in the mucosa, but the immune system wins out in the blood. The scientists found that antibodies in saliva attached to bacteria primarily via their Fc regions, but in blood the orientation was reversed, resulting in swift killing of the bug by immune cells. The orientation of binding was dictated by the local antibody concentration, namely the low antibody levels (as in saliva) favored Fc-mediated binding; high antibody levels (as in blood) favored Fab-mediated binding.
How this works is not entirely clear, but it's possible that the Fc binding proteins on the bacteria become saturated in the high-antibody environment of the blood, permitting free antibody to bind in the opposite orientation.