In this part of the chapter, we will examine how long-lasting protective immunity is maintained after an infection is successfully eliminated. Immunological memory is perhaps the most important consequence of an adaptive immune response, because it enables the immune system to respond more rapidly and effectively to pathogens that have been encountered previously, and prevents them from causing disease. Memory responses, called secondary immune responses, tertiary immune responses, and so on, depending on the number of exposures to antigen, also differ qualitatively from primary responses. This is particularly clear for B-cell responses, in that antibodies made during secondary and subsequent responses exhibit distinct characteristics, such as higher affinity to antigen compared with antibodies made during the primary response. Memory T-cell responses can also be distinguished qualitatively from the responses of naive or effector T cells, in terms of location, trafficking patterns, and effector functions.
11-17 Immunological memory is long lived after infection or vaccination.
Most children in developed countries are now vaccinated against measles virus; before vaccination was widespread, most were naturally exposed to this virus and developed an acute, unpleasant, and potentially dangerous illness. Whether through vaccination or infection, children exposed to the virus acquire long-term protection from measles, lasting for most people for the whole of their life. The same is true of many other acute infectious diseases (see Chapter 16): this state of protection is a consequence of immunological memory.
Because smallpox has been eradicated, recall responses measured in people who were vaccinated for smallpox can be taken to represent true memory in the absence of reinfection. After smallpox vaccination, antibody levels show an early peak with a period of rapid decay, which is followed by long-term maintenance that shows no significant decay. CD4 and CD8 T-cell memory is long lived but gradually decays, with a half-life in the range of 8–15 years.
The basis of immunological memory has been difficult to explore experimentally. Although the phenomenon was first recorded by the ancient Greeks and has been exploited routinely in vaccination programs for more than 200 years, it was recognized only within the last 30 years that this memory phenomenon reflects a small population of specialized memory cells that are formed during the adaptive immune response and can persist in the absence of the antigen that originally induced them. This mechanism of maintaining memory is consistent with the finding that only individuals who were themselves previously exposed to a given infectious agent are immune. The idea that immunological memory does not depend on repeated exposure to infection as a result of contact with other infected individuals has been supported by observations made of populations of people living on remote islands. In that setting, a virus such as measles can cause an epidemic, infecting all people living on the island at that time, after which the virus disappears for many years. On reintroduction from outside the island, the virus does not affect the original population but causes disease in those people born since the first epidemic.
The duration of immunological memory has been estimated by examining responses in people who received vaccinia, the virus used to immunize against smallpox (Fig. 11.23). Because smallpox was eradicated in 1978, it is presumed that their responses represent true immunological memory and are not due to restimulation from time to time by the smallpox virus. One study found strong vaccinia-specific CD4 and CD8 T-cell memory responses as long as 75 years after the original immunization, and from the strength of these responses it was estimated that the memory response had an approximate half-life of between 8 and 15 years. Half-life represents the time required for a response to diminish to 50% of its original strength. By contrast with T-cell memory, titers of antivirus antibody remained stable, almost without measurable decline.