Abstract: Series 113, Lecture 2
The Harvey Lectures Series 113 (2017—2018)
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Lecture #2: Thursday, November 16, 2017 — Watch Video of Lecture
Antibodies, Behavior and Cognition: Rethinking Immune Privilege
Betty Diamond, MD
Professor & Head, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research
Professor, Molecular Medicine and Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Director, PhD Program, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
The Feinstein Institute for Medical Research
Manhasset, New York
The brain has long been considered to be immune privileged and sequestered from systemic immune activation by the blood-brain barrier. There is, however, a growing appreciation of conditions characterized by brain-reactive antibodies. The hallmark of systemic lupus is anti-DNA antibodies, a subset of which cross reacts with NMDA receptors. When these antibodies penetrate the adult brain, they cause acute neuronal death followed by microglial activation, complement-dependent dendritic pruning of surviving neurons and cognitive impairment. These antibodies, when present in the blood of a pregnant woman, have unencumbered access to the developing fetal brain which lacks an intact blood-brain barrier. In utero exposure leads to abnormal cortical development and cognitive abnormalities in the offspring. These studies offer a paradigm for investigating the contribution of brain-reactive antibodies in acquired alterations in mood and cognition in adults and in congenital neuropsychiatric syndromes such as autism spectrum disorder, with implications for prevention or treatment.