I've got a 44 magnum so no need for me to use .22LR for home defense. But check out what 22LR fired from a rifle does to a gelatin block, if I had to use my 10/22, I would feel confident using it to defend myself but it still wouldn't be my first choice. A 22LR handgun I would not feel as confident with due to lower velocity and it would not be as accurate as a long gun and you do not have the larger caliber to compensate for the reduced accuracy of a handgun. If using 22LR to defend yourself, shot placement would have to be near perfect to a vital area. It is good to have a larger margin of error in a self defense situation so I prefer the larger calibers. A small fast moving bullet like the 17 HMR I would think would be likely to fragment and not penetrate deep enough.
G19, G20, G23