Because the Americas were isolated while Europe had engaged in extensive trade with the middle east, asia, and africa for centuries. European resistance to disease did not come free, it came at the cost of having lived through several catastrophic pandemics. The black plague (among other endemic diseases such as smallpox, measles, cholera, and malaria) killed hundreds of millions of Europeans, the Europeans of the 15th century were the descendants of the survivors of past outbreaks.