To cite two authoritative sources:
Paris Theodore, father of the Asp 9mm pistol and Seventrees holsters, carried a Walther PP .22 lr for self defense on the basis that no pistol calibre was a true stopper so he had just as well use something he could shoot very accurately; a portable launcher for a "supersonic telephone pole" not being available.
Jeff Cooper, Guru of the 1911 .45, said that a .22 would be suitable for self defense if you could hit a tennis ball from anywhere on the court. And presumably would use that accuracy to make good hits on an assailant.
Which brings up an interesting legal point. To STOP with a smallbore, you must KILL with it. You have heard .22, .25, and .32 pistols called "face guns?" That is because they can be counted on for immediate effect only if you shoot an assailant in the face and put a bullet up his nose or through an eye into his brain. Does your DA know or care?
The technical argument against a .22 for defense is the rimfire cartridge's lesser ignition reliablility than a centerfire. Distribution of priming compound can be uneven, as can brass rim thickness. I have seen many a .22 fail to fire on the first attempt but shoot when rehit at a different location on the rim. The 1860 Henry .44 Rimfire Flat had a double firing pin for good reason. The Freedom Arms .22 has one, too, but it probably is meant to get better accuracy with two site ignition, not reliablility in combat.