Clonal selection explains antibody specificity. It also explains the second feature of the adaptive immune system: the ability to remember past infections—that is, to react more vigorously on re-exposure. The first encounter with an antigen leads to a primary response (Fig. 43.12). In this response, there is a short lag before antibody is produced. The lag is the time required for B cells to divide and form plasma cells. The plasma cells secrete antibodies, typically IgM. The level of IgM in the blood increases, peaks, and then declines.

On re-exposure to the same antigen, even months or years after the first exposure, there is a secondary response, which is quicker, stronger, and lasts longer than the primary response (Fig. 43.12). During this response, memory B cells differentiate into plasma cells that release IgG antibodies. These memory B cells respond more quickly to antigen exposure than naïve B cells (B cells that haven’t been previously exposed to antigen). In addition, the pool of memory B cells is larger than the pool of naïve B cells for a given antigen, explaining why the secondary response produces more antibodies for a longer period of time.

The presence of long-lived memory cells produced following the primary response provides long-lasting immunity after an infection such as chicken pox. We have learned to make use of immunological memory in vaccination. Vaccination involves deliberately giving a patient an antigen from a pathogen to induce a primary response but not the disease, thereby providing future protection from infection by the same pathogen.

Vaccination was discovered by a combination of observation and experiment. Until the early 1700s, it was common practice to inoculate people with smallpox to induce a mild disease and prevent a more severe, even lethal, infection. It was also well known that milkmaids, exposed to the relatively benign cowpox virus from milking cows, were immune to the related but more deadly smallpox virus. In 1796, the English scientist Edward Jenner specifically tested the consequences of exposure to cowpox by inoculating a young boy with cowpox and demonstrating that he became immune to smallpox. In fact, the word “vaccine” is derived from the Latin vacca, which means “cow.”

Today, vaccines take many forms: They can be a protein or a part of a protein from the pathogen, a live but weakened form of the pathogen, or a killed pathogen. They are among the most effective public health measures ever developed.

Quick Check 2 Look again at Fig. 43.12. Imagine that a different novel antigen is added on day 40 rather than a second injection of the same antigen. Would you predict that there would be a primary or a secondary response to this second antigen?