CHDD Preventing Infections, Protecting the Developing Brain

�� SPRING 2006 VOL. 17, #1 INSIDE Expanding ASD Medical Services ....3 Pediatric Neurogenetics Clinic ..........4 Thousands of Genes at a Time: Microarray Services ...........................5 New Research Affi liates ....................8 NEWS FROM THE CENTER ON HUMAN DEVELOPMENT AND DISABILITY AT THE UNIVERSITY OF WASHINGTON HEALTH SCIENCES CENTER Preventing Infections, Protecting the Developing Brain NFECTIONS BEFORE AND Innate immune cells after birth are a major also initiate a cascade of I cause of developmental chemical signals, including disabilities. Take herpes cytokines, needed to activate simplex. In adults, this virus the acquired immune causes cold sores and genital system, which includes herpes, conditions that can be T cells, antibodies, and uncomfortable, but not life other defenses against threatening. However, herpes specifi c pathogens. If the simplex can kill newborns. It acquired immune system can also cause brain lesions has already encountered the that may result in a wide range pathogen in question, an of developmental disabilities, effective response develops depending on which parts of in just a matter of hours the brain are damaged. or days. However, if the Infants are more acquired immune system vulnerable to infection than is encountering a pathogen adults because their immune for the fi rst time, it requires systems are still maturing. “Infants are slower to develop much more time to provide an effective immune response protection: one to two weeks to infection and their response in adults and up to several Illnesses that cause only minor symptoms in adults can lead to developmental weeks in infants. Similar may be less robust,” said disabilities in unborn and newborn children. CHDD researcher Chris Wilson is delays occur in developing Christopher Wilson, M.D., studying ways to protect newborns by boosting their immune systems. research affi liate at the Center acquired immunity in on Human Development and response to vaccines. Disability (CHDD), chair of immunology, on pathogens and are found in cells of Unlike the acquired immune system, and professor of pediatrics. “Newborns the innate immune system, which serve which “learns,” expanding its capabilities also don’t respond as effi ciently to most as the body’s fi rst responder to infection. as it is exposed to new infectious agents vaccines as adults,” said Wilson. When a TLR alerts an innate immune cell and vaccines, the innate immune system Wilson studies the development of to the presence of a pathogen, it triggers a is genetically hard-wired to recognize a the immune system to fi nd ways to protect general attack on all potential pathogens fi xed, limited number of signals mediated very young children from herpes simplex by TLRs. So far researchers have identifi ed and other pathogens. His goal is to identify ten TLRs in humans. For example, one adjuvants, compounds that boost the “Our goal is to . improve vaccine TLR detects lipopolysaccharides, large immune system, and use these to make effi cacy early in life.” molecules found only in the membranes of gram-negative bacteria. Other TLRs vaccines more effective in young infants. - Christopher Wilson Specifi cally, Wilson researches how detect structures from viruses, fungi, and the immune response in infants may parasites. Many of the TLRs in humans refl ect reduced or qualitatively different in a matter of hours. The innate immune are very similar to TLRs found in other responses to signals received by Toll-like response can include the redness, swelling, mammals, as well as in birds, reptiles, and receptors (TLRs). TLRs detect structures and fevers associated with infection. insects. See ‘Immune Boost’ on page 2 CHDD OUTLOOK SPRING 2006, VOL. 17, #1 1 CHDD OUTLOOK is published by the Center on Human Immune Boost . from pg. 1 Development and Disability (CHDD) at the University of Washington Health Sciences Center. An online version can be downloaded from All infants are born with TLRs. http://www.chdd.washington.edu/gist/outlook.html However, the signaling system initiated by TLRs appears not to be fully functional CHDD is an interdisciplinary center dedicated to the prevention at birth. Some researchers theorize that an and amelioration of developmental disabilities through research, infant’s immune system has to be primed by training, clinical service and community outreach. CHDD includes the University Center of Excellence in Developmental Disabilities and environmental exposures. “The idea is that the Mental Retardation and Developmental Disabilities Research the only difference between the immune Center. systems of infants and adults is that newborns have been living in a sterile environment, and Address correspondence to: then they’re dropped into a dirty world and CHDD OUTLOOK Center on Human Development and Disability it takes a while for things to kick in,” said University of Washington Wilson. Another theory is that the pace of Box 357920 immune system development is genetically Seattle, Washington 98195-7920 determined. [email protected] “Our goal is to try to understand Christopher Wilson http://www.chdd.washington.edu the extent to which these differences are fi xed and immutable, that is hard-wired in Writer, editor, and photographer: Kris Freeman development, or are in fact subject to modifi cation by appropriate environmental Center on Human Development and Disability cues,” said Wilson. These cues could include agonists, compounds that bind to and stimulate TLRs. “The immune system of infants may require different kinds Michael J. Guralnick, Ph.D., Director of signals or more robust signals to achieve immunity than the immune systems Christene James, Administrator of older children,” said Wilson. Wilson’s research program has three primary goals. The fi rst is to determine MENTAL RETARDATION UNIVERSITY CENTER in detail the immune responses of newborns as compared to adults. He and AND DEVELOPMENTAL FOR EXCELLENCE IN colleagues at the UCLA Center for Vaccine Research are studying a group of DISABILITIES RESEARCH DEVELOPMENTAL CENTER (MRDDRC) DISABILITIES (UCEDD) infants by measuring immune function at birth, age seven months, and age sixteen months. Donald F. Farrell, M.D., Adults and Elders Program His second goal is to defi ne the molecular mechanisms responsible for Kathleen Watson, Ph.D., Associate Director, the differences in immune function observed between infants and adults. For Interdisciplinary Research Director example, Wilson and colleagues, including Samuel Miller, M.D., professor of Albert R. La Spada, M.D., Ph.D., Autism Center medicine, of microbiology, and of genome sciences, have identifi ed the structure Associate Director, Geraldine Dawson, Ph.D., Director that allows Pseudomonas aeruginosa to evadeevade detection byby TLR4 in the immune Research Development systems of infants and ill adults. , a common bacterium found in the Center on Infant Mental P. aeruginosa MRDDRC CORE SERVICES Health and Development human intestine, can cause swimmer’s ear and hot tub rash in healthy adults and Kathryn Barnard, Ph.D., Director extremely serious infections in infants, persons with cystic fi brosis, and cancer and Behavioral Science Core burn patients. Wilson also studies the immune response to the bacterium Listeria Susan Spieker, Ph.D., Center for Technology Director and Disability Studies monocytogenes, which can cause severe developmental disabilities. Kurt Johnson, Ph.D., Director Wilson’s third research goal is to identify TLR agonists that might serve as Genetics Core adjuvants, compounds that can boost or trigger the immune system, including the Albert R. La Spada, M.D., Ph.D., Clinical Training Unit activity of vaccines. “Our number one goal is to develop ways to improve vaccine Director John F. McLaughlin, M.D., Director effi cacy early in life,” said Wilson. A hepatitis B vaccine that uses a TLR adjuvant Infant Primate Research was recently approved for use in Europe. Laboratory Community Disability Policy Initiative To test adjuvants for their possible use in human infants, Wilson and his Thomas M. Burbacher, Ph.D., Sharan Brown, J.D., Ed.D., Director colleagues are developing mouse models that respond to TLR agonists the same way Director that humans do. “The TLRs in mice and humans differ in some important ways Instrument Development Experimental Education Unit and one of these differences affects responses to neonatal pathogens and adjuvants,” Laboratory Richard Neel, Ph.D., Director said Wilson. “So what we’re doing is creating mice that have human receptors Kirk Beach, M.D., Ph.D., rather than mouse receptors.” These animal models will be used to test the ability Director Genetics Program of different adjuvants to improve protection when they are administered together Thomas Bird, M.D., Co-Director Neuroscience Core with vaccines, with the expectation that their responses will more closely predict Kenneth Maravilla, M.D., what would occur in humans. A goal would be “to provide children with immediate protection at the same time they’re developing a protective immune response to the vaccine,” said Wilson. ♦ 2 CHDD OUTLOOK Expanding Medical Care for Children with Autism Spectrum Disorders some ritualistic behaviors and aggression, can be associated with the underlying pain and stress associated with these medical conditions,” said Geraldine Dawson, Ph.D., director of the Autism Center, CHDD research affi liate, and professor of psychology. Some researchers hypothesize that some episodes of self-injurious behaviors, such as biting or head banging, may cause

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