In history you hear of the great devastation that diseases such as smallpox did to isolated continents such as the Americas, but you never hear about Japan having such issues even after long periods of isolation.
Well, two things.
One, Japan was not that isolated. Foreign contact never really stopped, they were just limited.
Two, foreigners did bring deadly diseases to Japan. There were heavy smallpox outbreaks in the 8th century and beyond, syphilis was introduced in the Sengoku and caused lots of suffering, and cholera was introduced in the 19th century, leading to major outbreaks in 1822, 1858, and 1862.
A followup question - while Japan was relatively isolated, did it have regular trade or other contact with the Asian mainland? Did it have enough contact to be exposed to Eurasia's diseases?