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Unformatted text preview: F R A N K M . B U R N E T Immunological recognition of self Nobel Lecture, December 12, 1960 I like to think that when Medawar and his colleagues showed that immuno- logical tolerance could be produced experimentally the new immunology was born. This is a science which to me has far greater potentialities both for practical use in medicine and for the better understanding of living process than the classical immunochemistry which it is incorporating and super- seding. In this lecture I shall be concerned almost exclusively with theoretical aspects of immunity. Professor Medawar has spoken of the experimental aspects of acquired immunological tolerance and other types of immuno- logical non-reactivity and he has touched on the impossibility in natural chimeras of demonstrating that the genetically alien cells are treated in any way differently from cells that are genetically proper to the body. For me, acquired immunological tolerance means simply that the content of self components in the body has been enlarged by an experimental manipulation. Basically I shall deal in this talk only with a single problem. How does the vertebrate organism recognize self from not-self - in the immunological sense and how did this capacity evolve. The production of antibody is not the only, nor I believe the most impor- tant, manifestation of immunity, but for reasons both historical and of exper- imental convenience antibody is likely to remain the touchstone of immu- nological theory. Any formulation of theory must cover the nature of anti- body and lay down the conditions under which it will or will not be pro- duced. In this talk I am concerned for obvious reasons only with antigens derived from the cells of other vertebrates and tested for antigenicity in a defined species of mammal - in experimental work, rabbits and pure-line mice are the most usual but much work on the borderline between therapy and experiment has also been carried out in man. 690 1 9 6 0 F . M . B U R N E T Bovine serum albumin is antigenic in a rabbit, rabbit serum albumin is not. Both have presumably the same function in their proper species and the difference responsible for antigenicity can be regarded genetically as an ex- ample of neutral polymorphism. Superficially at least the differences seem to have no relevance to survival. Serum albumin is a well-defined protein but no laboratory has yet attempted to ascertain its full chemical structure. At present there are only two proteins whose primary polypeptide structure is known, insulin and ribonuclease, and only in the case of insulin have we information as to how structure varies according to the species from which the protein is derived. Insulin is a very poor antigen - otherwise we could not use bovine insulin successfully for the treatment of diabetes. Nevertheless it can function as an antigen in man and it is known that when immunolog- ical resistance develops to beef insulin, replacement by pig insulin will usually allow effective therapy.allow effective therapy....
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