existence of the belief that immunological memory comprises both short-
term and long-term memory.
6.3 SHORT-TERM AND LONG-TERM MEMORY
Short-term and long-term memory are not clearly defined in the literature, and their definition is complicated by the fact that most of the experiments are conducted on the murine immune system, and it is not always easy to extrapolate findings to a
relevant human time scale (Slifka et al 1998). However, in reference to humans, short-term memory is rarely defined, but is usually taken to be days or a couple of weeks, and long-term memory is generally a month or more (Colle, Truffa-Bachi & Freitas 1988).
It is believed that short-term and long-term immunological memory exist as distinct but complementary systems. The main reason for this belief is that we are exposed to such a wide range of pathogens it does not seem possible for the immune system to maintain life-long memory for all of them, and indeed the immune system does not. It is believed that long-term memory is required to protect against virulent but rarely encountered pathogens, and that short-term memory is required to deal with the range of pathogens constantly encountered in the immediate environment. However, this situation is complicated by the tendency of pathogens to evolve. This is particularly the case with viruses that mutate rapidly, for example influenza viruses, but is also true of more slowly evolving evolving pathogens such as measles or polio (Luria & Delbrück 1943).
However, a primary question here is ‘On what basis does the immune system select the pathogens to which it maintains a long-term memory?’ This question can usefully be viewed in terms of the logistics of information storage.
The question is about the dilemma facing a homeostatic immune system. Like librarians with limited shelf space, who must decide whether to keep old seldom-used texts or replace them with more current titles, the immune system must either keep memory T cells against rare antigens, though they may never again be needed, or make space for expansion of lymphocytes against pathogens in the immediate environment. (Matzinger 1994, p 605)
It is believed that the mechanisms involved in short-term and long-term immunological memory are different (Matzinger 1994).
Matzinger holds that short-term memory is partly a function of the follicular dendritic cells (FDC’s) of the lymphatic system, which bind antigen on their surface. During the initial infection with a pathogen, for example a virus, T and B cells specific to that virus are formed to help clear the infection. It is postulated that some antigen becomes bound to the surface of local FDC’s and then is slowly released. Once released, this antigen is captured by the virus specific B cells, which process and present them to the memory T cells. This keeps the response going for some months, although it will eventually wane as the store of antigen on the FDC’s is used up.
If the pathogen is common in the environment, the constant restimulation provided by repeated exposure will maintain the short-term memory. However, if the
pathogen is rare, the short-term memory response will eventually disappear and any subsequent reinfection will elicit the same response as an initial infection. This appears to be what happens particularly with localized mucosal infections such as rotavirus, respiratory syncitial virus (RSV) and various rhinoviruses (Ahmed & Gray 1996). This may be one reason why it has proven difficult to formulate effective vaccines for these pathogens.
6.3.2 LONG-TERM MEMORY
Long-term immunological memory has been known about for centuries. The evidence for its existence is based on the traditional observation that individuals who have survived a virulent disease rarely succumb to it again. The Greek
historian Thucydides, when writing about the plague of Athens in 430 BC noted that “the same man was never attacked twice” (Finley 1951).
Detailed documentation of long-term immunological memory was obtained in the isolated Faroe Islands. Severe measles epidemics occurred sixty-four years apart,
in 1781 and in 1846. The second epidemic was carefully documented by Panum, a Scandinavian surgeon, who observed that only individuals older than sixty-four who had measles during the earlier epidemic, did not contract the disease. This made the important point that immunity could be sustained in the absence of apparent re- exposure to the virus (Ahmed & Gray 1996; Matzinger 1994).
Long-term memory tends to be associated more with systemic infections. These are infections that involve the immune system as a whole, as opposed to a localized infection of, for example, the mucosal tissues of the respiratory tract. Systemic infections include diseases such as measles, yellow fever, polio, mumps and small-pox. These are diseases for which the most effective vaccines have been made, although generally the protection offered by these vaccines is not as long-lasting as that provided by natural infection (Ahmed & Gray 1996; Mackay 1993; Matzinger 1994). To understand why this is so will require a much better understanding of the mechanisms involved than currently exists, as even: