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offense commits holding, throws an interception, defense returns the ball, illegal block in the back on the return
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If you stopped right here, the Defense, as you put it, would have the option to decline the holding penalty and have their penalty enforced and keep the ball. However, the exception only exists for the team last gaining possession, and they must be "clean" prior to gaining possession.
The only other thing to remember is that any penalty may be declined. There are a few very narrow situations where fouls by both team have penalties that are declined and the result of the play stands. These are basically once a decade situations for officials but they have happened.
Note also that the NFL has different rules than Fed and NCAA do.