The correct answer is Option D) a lack of immunity to certain diseases.
During the mid-1800s, the greatest danger to American Indians in the West was a lack of immunity to certain diseases.
While the American Indians in the Eastern coast of the United States had all been wiped out, there were still plenty of Indian settlements in the Western part of the Continent.
By the 1800s, the United States was expanding westwards and as more and more White settlers moved to these places, they found tens of new tribes.
Many of these tribes were interacting with White settlers for the first time and were not immune to many of the simple diseases these settlers bought with them.
While accurate numbers are hard to find, many thousands of Indians died simply due to contracting diseases.