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.