watery depths of forgetfulness thanks to ages of ingenious psychological manipulation—-all knowledge of it has been repressed in human memory and when used as soon as the sign is released it is erased from memory.
This is what Dr. Sam Ferringo is referring to in the letter from Doris's father, where it mentions the "little t thing". It also referring to the Catholic/Christian/etc. faith in worship of God(Creator) who gave his only son to die on the cross.
D has almost complete defense against it. It does slight damage when he touches it leaving a burn looking mark, but he can heal from that near instantly when he releases it. And looking at it has no affect otherwise he wouldn't be able to make the sign himself.
D can also do a holy spell like he did in the first novel that uses the sign of the cross as a mark that only appears when a vampire's breath comes into contact with the person he puts it on. He also uses them as a grave marker in remembrance and reverence to the dead. So it not only has little affect he can also use holy spells using it to leave a special mark with it.