Getting 4 or 5 rounds in a chest is no easy feat. In fact it's mighty hard. I always point people to this video.
You'll see a man shooting his lawyer. He empties two .22 pistols at point blank range. Only 5 rounds hit the lawyer at all. Of those only 2 hit areas that are even close to being in vital areas. None of them were life threatening in any way. The lawyer walked away from the attack.
A .22 pistol is way better than nothing for defense. But comparing it to a large caliber gun reveals that it is extremely inadequate for self defense. People don't stand still and let you shoot them 5 times in the chest. They move to get away from being shot. It's not that easy to hit a moving target especially a human with a brain that knows by instinct how to avoid being hit by projectiles of any kind.
If you put even one round of .45 caliber ammo into a person the chances are it will severely affect that person. Even if the shot is only in the hand it will get the attention of the bad guy very quickly. People who get shot with a .22 often don't even realize they have been shot. Reagen didn't and he was an old man. The bullet "nearly" hit his heart but didn't. He was out of the hospital pretty quickly for an old guy because there wasn't that much damage.
Again a .22 is a poor example of a SD weapon. It's better than a sharp stick but not really that much better if you have a good sharp stick. I'm serious. They had these things called "spears" that were used very effectively in the days before firearms.
They can be used repeatedly and they can put big holes in people plus they can keep someone pushed back. I was joking when I made it look like people didn't know what a spear is. But I'm not joking when I say they are possibly more effective than a .22.
One more example. My wife's cousin was cleaning his .22. He managed to forget to unload it. He shot himself in the head. The bullet didn't penetrate his skull but traveled around the outside of his skull under his skin instead. Don't try that with a .45 or a .40 or a 9mm or even a .380. Don't try it with a .22 either but it is a fact that all those other calibers are far superior to a .22 when it comes to SD. .22's are for hunting small game or killing small varmints. If you want to stop a human use a much bigger caliber gun. You won't regret it. The idea of choosing a .22 for SD isn't a good one.
Size absolutely does matter - a lot.