BSCB Newsletter, Autumn 2008

3rd ENII-MUGEN Summer School in Advanced Immunology
4–11 May, 2008. Capo Caccia, Sardinia

The yearly Summer School in Advanced Immunology is organized through the European Network of Immunology Institutes (ENII) and brings together young scientists at doctoral or early post-doctoral level with a basic understanding of immunology, for a week of extensive teaching in all areas of immunology.

The 6-day school is centered on core seminars by prominent researchers in the field, combined with smaller tutorials or discussion groups and participants' poster sessions. The BSCB Honor Fell Travel award allowed me to attend this highly informative meeting at the end of my PhD, to broaden my immunological horizons and network with young immunologists from all over Europe.

The natural reserve of Capo Caccia is located in the northwestern part of Sardinia, a short bus drive away from the nearby airport of Alghero, and easy to reach by a number of European airlines. Nonetheless, many participants were grateful for the complimentary conference logo t-shirt distribution upon arrival while they were waiting for their lost luggage to follow. The summer school’s mission is twofold: to foster a deeper understanding of immunology in early-career researchers while creating an interactive atmosphere with great opportunities to socialize, network and build contacts that will strengthen the immunology field in Europe.

The six-day school was organized around daily main seminars from the guest faculty on major topics in the immunology field. Each afternoon, tutorial sessions offered a choice between any of the morning speakers, allowing participants to ask questions, deepen the subjects presented during the seminars and discuss in a relaxed atmosphere, often outdoors if weather permitting. Participants' poster sessions were held on four evenings after dinner, within the main hotel compound overlooking the scenic bay of Porto Conte, and were generally well attended by both students and the faculty members. The attractive setting and the closeness of the free hotel bar certainly encouraged enthusiastic discussions until well into the evening. Abstracts of particular interest had been selected by the conference panel for short oral presentations, which were held in five afternoon sessions and contributed to the broad spread of immunology topics covered during the conference.

Day 1 eloquently sold the message that seeing is believing, with Dimitris Kioussis (NIMR, Mill Hill, London) presenting his group's work on imaging lymphoid organogenesis in the mouse embryo using GFP-tagged lymphocyte markers, which also allowed to identify parallels between nervous system and lymphoid tissue organization in the developing gut. His talk was followed by Facundo Batista (Cancer Research UK, London), who presented fluorescence microscopy imaging at single molecule level of early signaling events in activated B cells, providing a mathematical model of the spreading and contraction response of activated B cells upon contact with antigen-presenting cells. After a short tea break, the morning session finished with an insight into the intricacies of the regulatory mechanisms of T cell receptor signaling by Oreste Acuto (Sir William Dunn School of Pathology, Oxford), who presented work on novel negative control nodes in the TCR signaling network.

The evening keynote lecture by Max Cooper (The University of Alabama at Birmingham, Birmingham, Alabama, US) explored the evolutionary origins of adaptive immunity in an unusual model system, the sea lamprey. Unlike bony fish, from which vertebrates derive, jawless fish like lampreys or hagfish have developed a completely independent system of their own, based on leucine-rich repeat domain-containing clonal receptors much resembling a B cell-like antibody repertoire capable of adaptation and memory.

The second day was entirely devoted to innate immunity, starting with an overview on macrophage biology in innate and adaptive immunity. After a historical perspective on phagocytes and the colorful variety of their surface receptors, Siamon Gordon (Sir William Dunn School of Pathology, Oxford) presented various aspects of macrophage biology, including pathogen clearance, adhesion and giant cell formation. Paola Castagnoli (Singapore Immunology Network, SIgN, Singapore) completed this overview with an introduction to the macrophage's sister cell, the dendritic cell, and presented comparative expression profiling data on the innate immune responses in Mycobacterium-infected macrophages and dendritic cells, proposing theories on the pathogen's ability to survive and replicate in the former but not the latter. The morning closed with an expedition into the world of cytoplasmic viral recognition and defense mechanisms by Caetano Reis e Sousa (Immunobiology Laboratoy, Lincoln's Inn Fields Laboratories, London), whose group identified the cytoplasmic helicase-like nucleotide sensor RIG-1 as a major factor in innate flu defense. The conundrum of why and how innate intracellular nucleotide sensors differentiate between pathogen- and host-derived agonists set the basis for an intense debate on self/non-self recognition during the afternoon tutorial session.

Day 3 gradually returned to adaptive immunity, and started off with Adrian Hayday (King's College, London) presenting the concept of transitional immunity, which describes the non-clonal, unconventional gamma-delta T cells populating the epithelia, capable of mounting rapid responses to stress-induced surface molecule expression on epithelial cells. Bernard Malissen (Centre d'Immunologie Inserm-CNRS, Marseille-Luminy, France) fully returned to conventional T cells, describing an unexpected T and B cell proliferative phenotype obtained by mutating a single phosphorylation site in the extensively studied LAT adaptor protein of the TCR signaling cassette. Finally, Fiona Powrie (Sir William Dunn School of Pathology, Oxford) presented work on the immune regulation in the intestine, dissecting the contribution of IL-12- and IL-23-mediated pathways to systemic and gut-specific inflammation, as occurs in chronic inflammatory states like inflammatory bowel disease.

After the free morning of Day 4, which most people used for a short excursion to the nearby fortified fishing port of Alghero, an afternoon of NK cell biology followed. James DiSanto (Institut Pasteur, Paris, France) started with a detailed overview of NK cell biology and outlined important questions in the field, such as haematopoietic origin of NK cells, homing to specific niches and conditioning of NK subsets. Angela Santoni (Università La Sapienza, Rome, Italy) extended this talk by addressing the balance of inhibitory and activating receptors on NK cells, which is conditioned by two sets of stimuli, missing self (e.g. absence of MHC class I molecules on virus-infected cells) or induced self (e.g. stress-induced surface expression of activating molecules, like MIC-A/B on tumor and virus-infected cells).

Paolo Vieira (Institut Pasteur, Paris, France) launched Day 5 with studies on fetal and adult B cell development, delineating the tightly regulated transcriptional activation at each developmental stage, and the crucial importance of IL-7 in orchestrating B cell lymphopoiesis. Anne O'Garra (NIMR, Mill Hill, London) continued with an extensive overview on the regulation of immune responses by cytokines, and Catherine Fridman (Cordelier Research Center, Paris, France) concluded the session with a presentation of Fc receptor biology and the therapeutic use of antibodies, delineating the various direct and indirect approaches in antibody-based anti-tumor therapy, as well as molecular engineering tools to improve antibodies for efficient therapy.

The final day's topic of anergy and tolerance certainly touched a chord in most over-stimulated participant brains. Bernd Arnold (DKFZ - Deutsches Krebsforschungszentrum, Heidelberg, Germany) gave a historical overview of the different definitions of tolerance and presented work from his group on dendritic cell-independent, tissue-induced or peripheral tolerance, as well as exciting unpublished results on a novel tolerogenic Wnt family member identified during gene expression profiling in tolerant CD8+ T cells. Maries van den Broek (Department of Oncology, Laboratory of Tumor Immunology, Zurich, Switzerland) further illustrated the complexity of priming and tolerisation of T cell responses, presenting the DIETER mouse model used in her laboratory to study the effect of specific T cell stimulation by engineered dendritic cells expressing the cognate T-cell specific epitope in the presence or absence of various co-stimulatory molecules. Luciano Adorini (Intercept Pharma, Perugia, Italy) concluded the last session with an excursion into the pharmaceutical world, presenting various immunology-based approaches for the treatment of autoimmune diseases.

The school’s location in an isolated place, with nature as only distraction, greatly fostered interaction between participants, helping to build useful networks for future collaborations with like-minded immunologists in Europe. In addition, the relaxed and open atmosphere provided many opportunities for one-to-one discussion with the faculty, of whom many remained present throughout the week. I highly recommend this summer school to interested students or early post-docs involved in any area of immunology, and would like to use this opportunity to advertise the 4th ENII-MUGEN summer school taking place 17-24 May 2009 in Capo Caccia, Sardinia, paired with the biennial EMBO-ENII Immunology Conference (for further information, go to www.enii.org).

Claudine Neyen,
Sir William Dunn School of Pathology,
Oxford