Blocking IPs without blocking WPMU

Howdy,
I'm using a variety of plugins from WPMU on my site(s) (shared hosting) and have started to look into my site visitors in order to eliminate unreasonable bot traffic.
I am starting my endeavor by blocking unrecognized IPs who seem to hit the site with high frequency and low duration.
I'd like to know if WPMU plugins, like Defender, use WPMU servers that I should be aware of so I do not unknowingly block them.
Thanks for any insight.