In 1660, Emperor Shunzhi's beloved consort Dong E died of smallpox; the following year, he also contracted the disease. When choosing his successor, he consulted the German missionary Johann Adam Schall von Bell, who recommended the 8-year-old Xuanye—later Emperor Kangxi. The reason: Kangxi had already survived smallpox, would not contract it again, and could rule for many years. And indeed, he became the longest-reigning emperor in Chinese history (61 years).

Though people did not understand why smallpox survivors never got it again, immunology now provides the answer: specific immunity.

The immune system has two branches: innate (non-specific) immunity and adaptive (specific) immunity. When pathogens invade, if they breach the first two lines of innate defense, the third line—specific immunity—takes over. Specific immunity is acquired after birth, targeting specific pathogens with specificity and immunological memory.

Specific immunity includes cellular immunity and humoral immunity, which work together. Lymphocytes—though only one-third of white blood cells—carry out the most critical immune tasks. Two types exist: T lymphocytes (mature in the thymus, lead cellular immunity) and B lymphocytes (mature in bone marrow, lead humoral immunity).

When stimulated by pathogens, T cells become sensitized T cells that release various lymphokines. Sensitized T cells have two key features: (1) ability to attack pathogens, and (2) recognition and memory—they keep a "record" of the criminal, enabling rapid response upon re-encounter.

B cells transform into plasma cells that produce antibodies, which dissolve pathogens, neutralize toxins, and agglutinate pathogens for phagocyte clearance.

When a previously encountered pathogen re-enters the body, sensitized T cells attack while antibodies bind and neutralize it. This is why smallpox survivors are immune—they retain specific immunoglobulins (antibodies) against the virus. However, these antibodies only protect against smallpox, not other pathogens.