The generative grammar of the immune system.

Grammar is a science that is more than 2000 years old, whereas immunology has become a respectable part of biology only during the past hundred years. Though both sciences still face exasperating problems, this lecture attempts to establish an analogy between linguistics and immunology, between the descriptions of language and of the immune system. Let me first recall some of the essential elements of the immune system, with which I shall be concerned. In 1890, von Behring and Kitasato (12) were the first to discover antibody molecules in the blood serum of immunized animals, and to demonstrate that these antibodies could neutralize diphtheria toxin and tetanus toxin. They also demonstrated the specificity of antibodies: tetanus antitoxin cannot neutralize diphtheria toxin, and vice versa. During the first 30 years, or more, after these discoveries, most immunologists believed that all cells of our body are capable of producing antibodies, and it took until the 1950s before it became clear, and until 1960 before it was demonstrated (13), that only white blood cells, named lymphocytes, can produce antibodies. The total number of lymphocytes represent little more than 1% of the body weight of an animal. Thus, it would not be wrong to say that our immune system is an organ consisting of about 1012 lymphocytes: (human) immune system = 1012 lymphocytes or in a mouse that is 3000 times smaller than we: (mouse) immune system = 3 x 108 lymphocytes This brief description of the immune system disregards the fact that lymphocytes interact with most other cells in the body, which in my definition do not belong to the immune system sensu stnictu. Let me draw attention to the fact that this number of lymphocytes in the immune system is at least one order of magnitude larger than the number of neurons in the nervous system. Also, we should note that lymphocytes travel among most other cells of our body, that they circulate in blood and lymph, and occur in large concentrations in spleen, lymph nodes, appendix, thymus and bone marrow. Strangely enough, however, they seem to be excluded from the brain. The 1960s was a very fruitful decade of immunological discoveries, of which I shall name a few: in the beginning of the decade, the primary structure of antibody molecules was clarified (14,15); then followed the demonstration that the dictum of Burnet (2,16) was correct, namely that all antibody molecules synthesized by one given lymphocyte are identical, and finally, towards the end of that decade, lymphocytes were shown to fall into two classes, called T cells and B cells, existing in the body in almost equal numbers (17,18,5). Only B lymphocytes, or B cells, however, can produce and secrete antibody molecules. Schematically, I could picture this as in Figure 1.