FYI The following ad-hoc seminar will take place this afternoon. It is being given by a collegaue of mine who is interested in non-invasive imaging of immune systems. The seminar though is purely about immunity Gary ---------------- AD HOC INFECTION AND IMMUNITY SEMINAR Wednesday 24 July, 4.00pm Q014, Centre for Immunology and Infection Professor Matthew Collin University of Newcastle "Human dendtiric cell homeostasis in vivo" Abstract: Over the last two decades, the study of human dendritic cells (DCs) has been driven by in vitro monocyte-derived models. Monocyte-derived DCs are competent antigen-presenting cells but do they really represent anything found in vivo? From the description of new subsets of primary human DCs, we have begun to understand more about the functional specialisation and homeostasis of human DCs in vivo. Haematopoietic stem cell transplantation highlights the differences between DCs and macrophages in turnover and immune function and provides insights into the induction of graft versus host responses. We have then turned to genetics and immunodeficiency to probe the homeostasis of DCs in unperturbed states. Many genetic disorders of innate and adaptive immunity are known but until recently, defined examples of DC deficiency had not been described in humans. We have developed simple tools to screen immunodeficient patients for DC deficiency and have identified a number of novel disorders, including IRF8 and GATA-2 mutation. Homozygous IRF8 (K108E) mutation leads to DC and monocyte deficiency with myeloproliferation. Heterozygous loss of GATA-2 function causes a failure of mononuclear cell development known as DC, monocyte, B and NK lymphoid (DCML) deficiency, associated with attrition of multi-lymphoid and granulocyte macrophage progenitors and elevated Flt-3 ligand. Examination of pedigrees with inherited GATA-2 mutation reveals individuals carrying mutant alleles that remain unaffected for several decades, indicating that DC and other mononuclear cells are intact at birth, and that immunity is not impaired until later in life. In this setting, normal immunoglobulin titres and memory T cell function preserve secondary immune responses long after DC function has declined. GATA-2 deficiency thus provides insights into human DC function and immunological memory in vivo. Bio: Matthew Collin is Professor of Haematology at Newcastle University and Director of Haematopoietic Stem Cell Transplantation at the Northern Centre for Cancer Care at the Freeman Hospital in Newcastle. He graduated with an MD/PhD from Oxford University in 1995 completing a PhD on HIV infection of macrophages in the lab of Siamon Gordon. He received funding from Leukaemia and Lymphoma Research (UK) as a Clinician Scientist and Bennett Fellow and completed post-doctoral work in the labs of Derek Hart and Miriam Merad. -- --------------- Gary Green York Neuroimaging Centre The Biocentre York Science Park Innovation Way Heslington York YO10 5NY http://www.ynic.york.ac.uk https://www.ynic.york.ac.uk/about-us/people/ggrg tel. Claire Fox : +44 (0) 1904 435329 Claire,Fox(a)ynic.york.ac.uk fax +44 (0) 1904 435356 mobile +44 (0) 788 191 3004