Abstract: Series 113, Lecture 2

The Harvey Lectures Series 113 (2017—2018)

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Lecture #2: Thursday, November 16, 2017 — Time and Location

Antibodies, Behavior and Cognition: Rethinking Immune Privilege

Betty Diamond, MD

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

Dr Diamond's Website

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.