Immunological Memory
When we make an immune
response to a given infectious agent, by definition that microorganism must
exist in our environment and we are likely to meet it again. It would make
sense then for the immune mechanisms alerted by the first contact with antigen
to leave behind some memory system that would enable the response to any
subsequent exposure to that particular antigen to be faster and greater in
magnitude.
Our experience of many
common infections tells us that this must be so. We rarely suffer twice from such
diseases as measles, mumps, chickenpox, whooping cough, and so forth. The first
contact clearly imprints some information, imparts some memory,
so that the body is effectively prepared to repel any later invasion by that
organism and a state of immunity is established.
Secondary immune responses are better
By following the
production of antibody and of effector T‐cells on the first and second contacts
with antigen, we can see the basis for the development of immunity. For
example, when we inject a bacterial product such as tetanus toxoid into a
rabbit, for the reasons already discussed, several days elapse before antibody
production by B‐cells can be detected in the blood; these antibodies reach a
peak and then fall (Figure 2.12). If we now allow the animal to rest and then
give a second injection of toxoid, the course of events is dramatically
altered. Within 2–3 days the antibody level in the blood rises steeply to reach
much higher values than were observed in the primary immune response.
This secondary immune response then is characterized by a more
rapid and more abundant production of antibody resulting from the “tuning up”
or priming of the antibody‐forming system. T‐lymphocytes similarly exhibit
enhanced secondary responses, producing cells with improved helper or cytotoxic
effector functions.
The fact that it is
the lymphocytes that are responsible for immunological memory can be
demonstrated by adoptive transfer of these cells to another
animal, an experimental sys tem frequently employed in immunology. The
immunological potential of the transferred cells is seen in a recipient treated
with X‐rays that destroy its own lymphocyte population; thus the recipient
animal acts as a living “test tube” in which the activity of the transferred
lymphocytes can be assessed in vivo. Lymphocytes taken from an animal
given a primary injection of antigen (for example, either tetanus toxoid or
influenza hemagglutinin) and transferred to an irradiated host, which is then
boosted with the same antigen, give a rapid, intense production of antibody
characteristic of a secondary response (Figure 2.13a,d). To exclude the
possibility that the first antigen injection might exert a nonspecific stimulatory
effect on the lymphocytes, “criss‐cross” control animals are boosted by
injection with a different antigen to that given for the primary injection. In
these control animals only primary responses are seen to either antigen (Figure
2.13 b,c). We have
explained the design of the study in detail to call attention to the need for
careful selection of controls in immunological experiments.
The higher response
given by a primed lymphocyte population is due to the presence of T and B
memory cells which not only form a quantitatively expanded population of antigen‐specific
lymphocytes (Figure 2.11) but also are functionally enhanced in comparison to
the original naive lymphocytes from which they were derived.
