These "freezes" could be happening for a variety of reasons. Most likely this is not something within Twisted itself, but something within your application which is taking that 2-5 seconds and preventing the server from doing anything else.
It sounds like you've got a large, complex application, so rather than guessing at what it might be, I suggest you use a tool like twisted_hang
to identify where your application is getting stuck; that should give you some idea of what you could change.