Immunosenescence (Medical Intelligence Unit)

Human immunosenescence contributes to morbidity and mortality in later life. The age-associated increasing incidence of cancer and cardiovascular disease plateaus at around 80 years of age in industrialised countries, but death due to infectious disease continues to increase up to 100 years of age and beyond. Understanding the reasons for age-associated alterations to protective immunity in the elderly would facilitate the development of interventions to reconstitute appropriate immune function, increase responsiveness to vaccination and extend healthspan. The majority of the papers collected in this volume therefore address not only the mechanisms responsible for immune ageing in humans but consider what might be accomplished to redress the erosion of immune competence with age. The first problem facing the gerontologist investigating human ageing is their longevity: most studies are conducted in a cross-sectional manner, in which parameters of interest in elderly cohorts are compared to young controls. However, the ageing trajectories of people now 80 years old, born at the beginning of the 20th century, will have been very different in mostly unidentifiable ways from those born towards the end of that century. These differences include population genetics, nutrition, stress, disease, and of course, medical treatment, all of which make these two populations hardly comparable. Immunosenescence | Graham Pawelec, ed.......Page 2 ISBN 9780387768403......Page 3 C O N T E N T S......Page 5 Contributors......Page 9 Preface......Page 14 Acknowledgments......Page 16 Introduction......Page 17 NONA Immune Subjects......Page 19 Immune Parameters and Morbidity......Page 20 Immune Risk Phenotype, Cognitive Impairment and Mortality......Page 21 Allostatic Load......Page 22 IRP, T-Cell Differentiation and Persistent Viral Infection......Page 23 TCR Clonotype Mapping......Page 26 IRP Movement......Page 27 Conclusions and Future Directions......Page 28 Infection Is a Major Cause of Death in the Elderly......Page 31 A Significant Number of Cancer Patients Die of Infection......Page 32 Assessment of the Immunological State......Page 34 Restoration of Immune Function......Page 36 Effect of Infusing Activated T-Cells in the Mouse Model......Page 37 Introduction......Page 40 Expression of NKR on T-Cells in Ageing: Expansion of CD8 T-Cells Expressing NK Associated Receptors in the Elderly Is Due to the Expansion of Effector Memory 2 T-Lymphocytes......Page 41 CMV-Specific CD8 T-Cells Are Expanded in the Elderly Expression of NK Associated Receptors......Page 44 Concluding Remarks and Future Prospects......Page 46 Introduction......Page 50 Characteristics of Senescent CD8 TCells: Telomeres and CD28......Page 51 Telomerase: Connections between CD28 and Telomeres......Page 53 Replicative Senescence of CD8 T-Cells in HIV Disease......Page 54 Concluding Remarks......Page 55 Activation-Induced Cell Death (AICD)......Page 60 CD95-Mediated Apoptosis......Page 61 TNFR-Mediated Apoptosis......Page 62 Apoptosis of Subsets of CD4+ and CD8+ T-Cells in Human Aging......Page 66 Introduction......Page 73 Antigenic Stimulation of T-Cells with Aging......Page 74 Role of the Nutrition: Metabolic Syndrome and T-Cells......Page 80 Conclusion......Page 81 Common Ageing Signature......Page 84 Immunosenescence......Page 85 Age and Thymic Output......Page 86 Thymic Rejuvenation......Page 87 Autoimmune Responses, Gender and Age......Page 90 The Role of IL-7 and Autoimmunity......Page 91 Conclusions and Future Perspectives......Page 92 Autoantigens in IDDM and RA......Page 96 Influence of Infection......Page 97 Immune Aging......Page 98 Conclusion......Page 101 Introduction......Page 108 The Chemokine System......Page 109 Atherosclerosis......Page 110 Type 2 Diabetes......Page 113 Osteoarthritis......Page 114 Alzheimer's Disease......Page 115 Future Prospects......Page 116 Introduction......Page 122 Influenza......Page 123 Herpes Zoster......Page 127 Pertussis......Page 128 Travel Vaccines......Page 129 How Does Immunosenescence Influence Vaccine Efficacy?......Page 131 How to Improve Vaccine Efficacy in Old Age?......Page 132 Conclusions......Page 133 Introduction......Page 137 Zinc Deficiency in the Elderly......Page 138 Comparison of Immunosenescence and the Effects of Zinc Deficiency......Page 139 Zinc Supplementation and Immunosenescence......Page 140 Conclusions......Page 141 Introduction......Page 145 Metallothioneins and Ageing......Page 146 Zinc Transporters and Ageing......Page 148 Conclusions and Future Perspectives......Page 150 13. Immunogenetics of Aging......Page 153 Immunity and Aging......Page 154 Why MHC?......Page 155 HLA and Longevity......Page 157 Why Cytokines?......Page 159 Gene Polymorphism of Proinflammatory Cytokines and Aging......Page 160 Conclusions......Page 164 Introduction......Page 170 CDl4 and Toll-Like Receptor 4 (TLR4)......Page 173 IL-l Cluster......Page 176 IL-6......Page 178 IL-I0......Page 179 Interferon (IFN)-y......Page 180 Chemokine-CC-Motif-Receptor 5 (CCR5)......Page 181 Cyclooxygenase(Cox), Lipoxygenase (Lox)......Page 182 Conclusions......Page 184 15. SELDI Proteomics Approach to Identify Proteins Associated with T-Cell Clone Senescence......Page 190 Introduction......Page 191 SELDI-MS Protein Profiling of T-Cell Clones Derived from Young and Old Donors......Page 193 Identification of Differentially Expressed Protein/Peptide Peaks......Page 194 Results......Page 195 Index......Page 207 Immune risk phenotypes and associated parameters in very old humans : a review of findings in the Swedish NONA immune longitudinal study / Anders Wikby ... [et al.] Scoring of immunological vigor : trial assessment of immunological status as a whole for elderly people and cancer patients / Katsuiku Hirokawa ... [et al.] Remodelling of the CD8 T-cell compartment in the elderly : expression of NK associated receptors on T-cells is associated with the expansion of the effector memory subset / Inmaculada Gayoso ... [et al.] Telomeres, telomerase, and CD28 in human CD8 T-cells : effects on immunity during aging and HIV infection / Steven R. Fauce and Rita B. Effros A matter of life and death of T-lymphocytes in immunosenescence / Sudhir Gupta T-cell signalling, a complex process for T-cell activation compromised with aging : when membrane rafts can simplify everything / Tamas Fulop... [et al.] Immunosenescence, thymic involution and autoimmunity / Wayne A. Mitchell and Richard Aspinall. Autoimmune diseases, aging and the CD4+ lymphocyte : why does insulin-dependent diabetes mellitus start in youth, but rheumatoid arthritis mostly at older age? / Jacek M. Witkowski Role of chemokines and chemokine receptors in diseases of ageing / Erminia Mariani, Adriana Rita Mariani and Andrea Facchini The efficacy of vaccines to prevent infectious diseases in the elderly / Dietmar Herndler-Brandstetter and Beatrix Grubeck-Loebenstein Zinc and the altered immune system in the elderly / Hajo Haase and Lothar Rink. Zinc-binding proteins and immunosenescence : implications as biological and genetic markers / Eugenio Mocchegiani and Marco Malavolta Immunogenetics of aging / Elissaveta J. Naumova and Milena I. Ivanova The genetics of innate immunity and inflammation in ageing, age-related diseases and longevity / Calogero Caruso ... [et al.] SELDI proteomics approach to identify proteins associated with T-cell clone senescence / Dawn J. Mazzatti ... [et al.]. Human immunosenescence contributes to morbidity and mortality in later life. Understanding the reasons for age-associated alterations to protective immunity in the elderly would ultimately improve and extend healthspan. The majority of the papers collected in this remarkable and timely volume address the mechanisms responsible for immune ageing in humans. They also consider what might be accomplished to redress the erosion of immune competence with age. Human immunosenescence contributes to morbidity and mortality in later life. This title collects papers that address the mechanisms responsible for immune ageing in humans and considers what might be accomplished to redress the erosion of immune competence with age