If I had to use a .22 for self defense I suspect the best strategy would be to aim for the hip joints. If you cause them to no longer be able to ambulate you have prevented them from coming after you. This a strategy hunters use on dangerous game. They shoot the joints to prevent the animal from reaching them. Then they are able to take a head shot at their leisure.

On the other hand if they have a gun you better hope they are a bad shot