How/when do responses happen?

In other words, if Meera Reed is in my hand, can I use her response (Response: After a *Stark* character leaves play, put Meera Reed into Shadows.) if she is in my hand?

Or does it only apply if she is "in play" -- either in Shadows or revealed?

Thanks!

The card has to be in play unless it says otherwise in the action's description.

Also note that cards in shadows are not in play. The shadows areas is like an extra hand, an out-of play area where only you know the cards, while everyone knows how many there are.