The Immunology of Ageing

London, London
Monday, 24 February 2014

This is a Euroscicon Small Conference,  an outline of the day can be found at 
www.euroscicon.com/EurosciconMeetingStructure.pdf

This event will be held at The O2,  a large entertainment district on the Greenwich peninsula in South East London, England.

The Immunology of Ageing
Monday, 24 February 2014 09:30 - 17:00

Cineworld: The O2
Peninsula Square
London
London
SE10 0DX
United Kingdom

Map and Directions
It is clear that the immune system undergoes age-associated alterations, producing a progressive deterioration in the ability to respond to infections and to develop immunity after vaccination. This event will discuss this Immunosenescence, both within the innate and adaptive immune systems. While discussing the mechanisms that contribute to immunosenescence, there will be plenty of networking opportunities and also debate  relating to potential therapies that could be employed to help the population live longer, fuller and healthier lives. This event has CPD accreditation. This event is part of the 2014 Ageing Summit: www.AgeingSummit2014.com



Meeting Chairs:   Dr Neil A Mabbott, The Roslin Institute& Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Scotland, UK
Dr Milica Vukmanovic-Stejic, Senior Research Fellow, UCL Medical School, London, UK


Talks include
Old B cells, what are the chances they will help us?
Dr Deborah Dunn-Walters,
Reader in Immunology, Department of Immunobiology, King's College London School of Medicine, UK
A diverse B cell repertoire is essential in order to increase the chances of being able to recognise foreign antigen. At the same time the repertoire has to avoid carrying specificities for self antigens.  Older people are more prone to infection, less able to respond well to vaccine and generally have more autoantibodies in their blood.  We will discuss this in the context of our findings on B cell repertoire changes with age, and different types of B cells that respond to different types of antigen challenge.

Effects of ageing on antigen sampling in the mucosal immune system
Dr Neil A Mabbott
, The Roslin Institute & Royal (Dick) School of Veterinary Sciences, University of Edinburgh, UK
The gastrointestinal tract is continuously exposed to large amounts of commensal and pathogenic microorganisms. As well as mounting an effective immune response against food-borne pathogens, the mucosal immune system must also recognise the harmless antigens (Ag) associated with food and commensals and generate immunological tolerance against them.  The transcytosis of Ag across the follicle-associated epithelium (FAE) of Peyer’s patches by M cells is important for the induction of efficient immune responses to mucosal antigens.  The mucosal immune response is compromised by ageing, but effects on M cells were unknown. We show that M-cell density in the FAE of aged mice was dramatically reduced.  As a consequence, aged Peyer’s patches were significantly deficient in their ability to transcytose particulate lumenal antigen across the FAE.  Ageing specifically impaired the expression of Spi-B and the down-stream functional maturation of M cells.  Ageing also dramatically impaired CCL20 expression by the FAE.  As a consequence, fewer B cells were attracted towards the FAE, potentially reducing their ability to promote M-cell maturation.  These data show that ageing dramatically impedes the functional maturation of M cells, revealing an important ageing-related defect in the mucosal immune system’s ability to sample lumenal antigens.

Para-inflammation and Age-related Macular Degeneration
Dr Heping Xu,
Centre for Vision and Vascular Science (CVVS) Queen's University Belfast Institute of Clinical Science, Ireland
Para-inflammation is an immune response to chronic noxious stimuli at a low magnitude that lies between the basal homeostatic state and overt inflammation. The physiological role is to maintain tissue homeostasis and functionality. Dysregulation in the para-inflammatory response underlies many chronic diseases such as diabetes, atherosclerosis and various age-related degenerative disorders. The nature of retinal para-inflammation under normal ageing conditions and the role of dysregulated or maladapted para-inflammatory response in age-related macular degeneration will be discussed.

Lymphocyte proliferation, ageing and the regulatory proteolysis of key proteins.
Professor Jacek Witkowski
, Department of Pathophysiology, Medical University of Gdansk, Poland
Cells control the activities of their proteins by limited regulatory proteolysis (LRP). The ‘calpain-calpastatin system’ (CCS) regulates the activities of signal transduction molecules, receptors, transcription factors and elements of cell division ‘machinery’ known to be modified by ageing, and thus is an important object in the study of immunosenescence and longevity. We have recently launched an international project (CALPACENT®) aiming at defining the role of CCS in the wellbeing of the immune systems in centenarians. We will discuss the results obtained so far in the context of dwindling performance of ageing immune system and of current understanding of cellular LRP.

Effects Of Melatonin On The Age-Dependent Dysregulation Of The Nf-Kb/Nlrp3 Activation During Sepsis
Mr. Huayqui Volt Valdivia,
Biomedical Research Center, University of Granada, Spain
The age-related changes of the immune system involve a persistent proinflammatory state. This subclinical and chronic inflammation contributes further to enhance the susceptibility of the elderly patients to several acute and chronic inflammatory diseases, including sepsis and ageing itself. The recent discovery of the NF-kB/NLRP3 connection during the innate immune response to inflammatory signals leads to explore the activation of this pathway during ageing in a mouse model of sepsis. The lack of an effective treatment of this disease supports the look for new molecular targets and/or drug therapy. We explored whether the anti-inflammatory actions of melatonin can protects against NF-kB/NLRP3 activation. Our results support NLRP3 inflammasome as a novel molecular signaling pathway during sepsis and indentify it as a main target for the anti-inflammatory action of melatonin. Due to the age-dependent reduction in the endogenous melatonin production, the relation between melatonin reduction and increased inflammatory response with age is discussed.

Ageing of the immune system – Role of CMV for Coronary Heart Disease
Professor Ioakim Spyridopoulos
, Chair of Cardiovascular Gerontology, Hon. Consultant Interventional Cardiology, Newcastle University and Freeman Hospital, UK
While human cytomegalovirus (CMV), a herpesvirus that is never cleared from individuals following primary infection, is deemed harmless in immunocompetent people, there is mounting evidence that it adversely affects human lifespan linked to a higher incidence of coronary heart disease (CHD) in seropositive individuals. This talk will look into the potential link between an ageing immune system, cytomegalovirus infection and progression of atherosclerosis. It will attempt to link cellular changes in the CD8 T cell compartment secondary to CMV, telomere biology and inflammation with the pathophysiology of coronary artery disease.

Old before our time? Cytomegalovirus establishes the rudimentary signs of an ageing immune system even in young and healthy adults.
Dr James Turner,
Lecturer, Department for Health, University of Bath, Bath, UK. Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process has been associated with increased susceptibility to infection, accelerated cognitive decline, frailty and increased mortality. It has become clear that many features of an ageing immune system are determined by Cytomegalovirus (CMV) infection. Until recently, it remained largely unexplored whether CMV drives immunity towards a senescent profile in young and healthy adults. In this talk I will present the results of a recent investigation, whereby several hallmarks of immunosenescence were assessed in a chronologically young population of healthy university students.

Insights into maintaining Immunsurveillance in Advanced Age: Killer Inhibitory Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Oct/Nonagenarians in  Belfast Elderly Longitudinal Free-living Aging Study (BELFAST)
Dr Irene Maeve Rea,
Senior Lecturer and Consultant Physician Geriatric Medicine , Queens University Belfast and Belfast Health and Social Care Trust, Northern Ireland
Natural Killer cell (NK) populations,  Killer Cell receptor complexes (KIRs) and associated cytokine profiles are highly effective collaborators in controlling, patrolling and protecting our immune landscape.The intrinsic and extrinsic factors that shape human NK cell diversity remain incompletely understood. In dissecting out elements of this immune landscape we have reported relationships between NK cells and NK-related subsets, KIR A and B haplogroups and cytokines as in subjects from the BELFAST study. The findings across the 3 interacting domains are exploratory but may serve to stimulate debate and encourage replication studies to improve our understanding about the immune signatures of those who live successfully into their 90s.

Meeting reports from this event will be published by Expert Review of Clinical Immunology and by HONNAO publishing

Keywords: B cells, repertoire, antibody genes, immunity, Ageing, para-inflammation, age-related macular degeneration, microglia, complement, Ageing, Cardiovascular, Telomeres, CD8 T lymphocytes, Cytomegalovirus, Immunosenescence, Cytomegalovirus, Vaccination, Interleukin-6, CD8+ T cells, Natural Killer Cell, Killer Inhibitory Receptor Haplogroup, Cytokine, longevity, Octo/nonagenarians, immunosenescence, T cells, calpain, cell cycle











 

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