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THE IMMUNE SYSTEM IN SLOW DISEASE DUE TO PERSISTENT SUBMICROBIAL (VIRAL) INFECTION ROBERT W. HUNTINGTON* andJOHN M. ADAMSf I. Introduction While the "unconventional viruses" or Gajdusek agents, which have not been found to elicit or interact with immune response, are still an amazing novelty, their role in slow disease has been admirably clarified in recent reviews [1, 2]. However, in the interaction with immune response in slow disease evoked by "conventional" viruses, reported findings are variegated and confusing. Here the writers, concerned with the pathologic and clinical implications of virology and immunology [3-8], find themselves much in need of perspective. The urgency of the need underscores the hazard ofattempting to fulfill it. In this venture we have benefited from helpful orientation in the comments of virologist and immunologist colleagues. We hope that the result ofour efforts may be helpful to others, at least as a point of departure. ?Address: 470 Wellington, Cambria, California 93428. Clinical professor of pathology emeritus, University of Southern California School of Medicine, Los Angeles, and director ofmedical services and consulting pathologist emeritus, Kern Medical Center, Bakersfield, California. tThis will be the last paper in Dr. Adams's bibliography, for he died on June 30, 1980, shortly after the acceptance of diis collaborative effort and 23 days after his seventy-fifth birthday. He took an incisive interest in this collaboration almost to the very end. It will be noted that, though its format is Huntington's, die ideas are ideas which Dr. Adams had held for some time. It will furtherbe noted that some ofthese ideas were so original when he first propounded them that it took some time before colleagues took them seriously! From the University of Minnesota, where he had been associate professor, Dr. Adams came to Los Angeles in 1950 as founding chairman ofthe Department ofPediatrics at die University of California at Los Angeles. Wishing to have more time for research, he relinquished die chairmanship in 1964. He assumed emeritus status in 1972. His previous bibliography includes, in addition to a few abstracts, three books and 123 other contributions. His major interest was in infectious disease. Never wavering in his primary commitment to the care of sick children, he became increasingly interested in late manifestations ofinfection acquired in early life. This interest led him into adult neurology and veterinary paüiology. He was deeply concerned with die possible role of persistent measles virus infection in multiple sclerosis. John Adams was a student in the true heroic mold, a student ofgreat perspicuity and tenacious originality, unswayed by winds of doctrine.©1981 by The University of Chicago. 0031-5982/81/2404-0239$01.00 Perspectives inBiology andMedicine · Summer 1981 \ 637 Since in the broad field to be covered psychological metaphor, exemplified in terms such as information, immunological memory, and surveillance , has been found helpful, we do not hesitate to speak of a trend in living entities toward maintenance and assertion of self, manifest in restriction of genomal modification and in reaction to intrusion by what is not recognized as self. The restriction and the reactivity are inconstant, becoming indiscernible in sexual reproduction with viviparity. We speak of both pathogenicity of infectious agents and immune responses of complex animal organisms as self-assertion. The mode of self-assertion may or may not be beneficial to the asserting entity. Thus high pathogenicity, though a persistent or recurrent habit among infectious agents, precludes the possibility of commensal or symbiotic relationships , which, while much more tolerable to the host, might also have been much more convenient for the agent. Immune response to infection may be helpful, inconsequential, or harmful to the infected animal. Response to the other (noninfectious) strange material is seldom helpful, and response to the animal's own tissue [9], which we speak ofas the result of failure to discern the line between self and nonself, can induce a variety of adverse effects. Diminution of inappropriate response is likely to involve diminution of desirable responses as well. Thus the sustained clinical belief in the particular hazards of certain infections in pregnancy accords with the notion of immunosuppressive backup of placental hypoantigenicity as one factor in the rather consistent success of intrauterine implantation of that allograft, the fetus...

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