While it's most common usage is in a comeback, it can also be the answer to a question, establish you dont want to continue the conversation, break the ice, initiate a romantic sequence, be an adjective, an answer to a knock knock joke, or just literally refer to a person's grandma; tu abuela in this sense is a little like Por las nalgas.
Javier: Tu abuela!!
Chris: Fine, be that way, but anyhow, you wanna go to the movies later?
Javier: Tu abuela bro, i really just dont know, have you asked Neo?
Chris: I did, but im getting the vibe he is feeling a little under the abuela today.