In the City of Rapture, the Little Sisters are young girls who have had a particular species of deep ocean sea slug embedded in their digestive tracts. The slugs were a source of ADAM, an incredibly powerful gene-altering stem cell compound, the foundation of a booming genetic modification industry based on the creation of plasmids.
Initially, Rapture's plasmid industry harvested the slugs directly, but they just couldn't produce the volume needed to support the thriving plasmid industry. Dr. Brigid Tenenbaum devised a process grafting the slugs into the digestive tracts of little girls. Initially they were kept in confinement as their bodies produced massive amounts of ADAM, which was then collected through induced regurgitation, but during the Rapture civil war the Little Sisters were re-purposed to extract ADAM directly from the the dead, by ingesting their blood. Since the sea slugs were embedded in their digestive tracts, the Little Sisters were capable of processing the ADAM directly from the blood serum of the deceased. The Little Sisters' bodies were saturated with ADAM from this process, and gained a form of immortality as a subsequent result. Little Sisters are always accompanied by a Big Daddy.
As harvestable NPCs, they are completely immune to damage and have no offensive attacks; attacking them, however, will incur the wrath of their Big Daddy protector. As escort NPCs, however, they are vulnerable to damage, perhaps because those particular Little Sisters aren't full of ADAM, as the "regular" ones are.