Antigen Specificity
Discrimination between different antigens
The establishment of
immunity to one microorganism does not confer protection against another
unrelated microorganism. After an attack of measles we are immune to further
infection but are susceptible to other agents such as the chickenpox or mumps
viruses if these have not been encountered. Acquired immunity shows specificity
and the immune system can differentiate specifically between the two
organisms. A more formal experimental demonstration of this discriminatory
power was seen in Figure 2.13, where priming with tetanus toxoid evoked memory
for that antigen but not for influenza hemagglutinin and vice versa.
The basis for this
lies of course in the ability of the recognition sites of the antigen‐receptor
molecules to distinguish between antigens; antibodies that react with the
toxoid do not bind to influenza and, mutatis mutandis as they say,
anti‐influenza does not recognize the toxoid. Similarly, T‐cell receptors are
specific for a given peptide (plus MHC) sequence derived from the antigen.
Discrimination between self and nonself
This ability to
recognize one antigen and distinguish it from another goes even further. The
individual must also recognize what is foreign (i.e., what is “nonself”). The
failure to discriminate
between self and nonself could lead to the
synthesis of antibodies (autoantibodies) directed against
components of the subject’s own body, which might prove highly damaging. On
purely theoretical grounds it seemed to Frank Macfarlane Burnet and Frank
Fenner that the body must develop some mechanism whereby “self ” and “nonself”
could be distinguished, and they postulated that those circulating body
components that were able to reach the developing lymphoid system in the
perinatal period could in some way be “learnt” as “self.” A permanent
unresponsiveness or tolerance would then be created so that as
immunological maturity was reached there would normally be an inability to
respond to “self ” components. Burnet argued that if, following clonal
selection, each set of lymphocytes were making their own individual specific
antibody, those cells programmed to express antibodies reacting with
circulating self components could be rendered unresponsive without affecting
other lymphocytes specific for foreign antigens. In other words, self‐reacting
lymphocytes could be selectively suppressed or tolerized without undermining
the ability of the host to respond immunologically to infectious agents. As we shall see in Chapter 10, these
predictions have been amply verified, although we will learn that, as new
lymphocytes differentiate throughout life, they will all go through this
self‐tolerizing screening process. However, self tolerance is not absolute and
normally innocuous but potentially harmful anti‐self lymphocytes exist in all
of us.
