How the immune system works to protect the host from infection: a personal view.

Abstract

When I was a young medical student, an interesting discussion was going on about how antibody diversity was encoded; was the antibody molecule encoded in many genes, one for each specificity, or were they general adaptor proteins that were formed on an antigen template. I understood the arguments, which were laid out by my laboratory instructor, Hugh McDevitt. He had just discovered immune response genes in the mouse and was soon to map them to the major histocompatibility complex, which was at that time only known to encode the antigens that provoked rapid graft rejection. I worked the summer after my second year at Harvard Medical School in Hugh's lab, after which I went to the National Institute for Medical Research to work with John Humphrey. In Hugh's lab, I was given the project of trying to make antibodies to L- and D-enantiomers of the same basic amino acids, called L- and D-TGA (for tyrosine, glutamic acid, and alanine). I spent 2 years in Humphrey's laboratory, spent much time in the library reading papers, and published three or four of my own. This was a period when little was known about immunology, as the idea of cutting and splicing genes lay ahead in the future. Antibodies were the only known specific products of lymphocytes, so we measured them in detail. But everyone I talked to in those years was full of ideas about how antibody diversity was generated and how, once generated, it remained the same or very similar throughout the course of a specific immune response. What I will describe in this essay is the growth of three ideas. The first is that the immune system is actually made up of two arms, one specific for infectious non-self, and the other specific for …