If we are talking Win10 I'd like to know why would you disable Windows Defender? Probably the lightest, most up to date and convenient anti-virus solution for Windows 10 at the moment?
I've ran my computer for years without anti-virus and I've had windows defender disabled for over a year now. I use host file blocks along with ublock origin. I keep malware bytes on standby.
i did it as i had a problem where it was taking up 100% of my ram for some reason which meant i couldnt use my pc at all until 15 minutes when it would turn back to normal after disabling it, it fixed the problem right away as long as your smart with what you download you should be fine without it