Re: .22 as a home defense gun?
Not so much the caliber as the ignition system is wrong.
The rimfire is simply not dependable enough. I've even had misfires with CCI, though that is rare.
Remember, back when they were using rimfire in large caliber blackpowder rifles, most had two or three firing pin strike points -- and even that wasn't an assurance of the thing firing.
Sealed centerfire ammo is what I'll continue using.