Basic Biology and Clinical Impact of Immunosenescence

by Pawelec

• ISBN13: 9780444513168
• ISBN10: 0444513167
• Edition: 1st
• Format: Hardcover
• Copyright: 2003-05-01
• Publisher: Elsevier Science
• More Book Details
• Purchase Benefits

Summary

Like other organ systems, the immune system does not remain unaffected by age. Work begun over three decades ago already hinted at the importance of immunity for the achievement of healthy old age. The real clinical relevance of age-related alterations in the immune system is, however, still remains controversial. This volume of ACAG contains contributions describing studies which are helping to resolve these difficulties, focussing predominantly on humans. The importance of longitudinal studies is stressed and the concept of an "immunological risk phenotype" is introduced, whereby clusters of immune parameters can predict morbidity and mortality. Current knowledge of age-associated changes in important immune system parameters are discussed in detail: T cells and NK cells, the role of cytokines and cytokine receptors, the impact of genetic factors, a critical role for the balance between inflammatory and anti-inflammatory activities within the immune system, and the role of chronic antigenic stress in determining immune parameters and overall longevity. Although all cells of the immune system show age-associated changes, it is the T cell compartment which is most severely affected. As T cells are generated primarily in the thymus, this organ must be the first focus of attention when considering T cell immunosenescence, as discussed in this volume. Peripheral T cell aging is considered in terms of alterations in signal transduction pathways required for activation of immune responses. The T cell arm is contrasted with an important compartment of the innate immune system, the neutrophil. Costimulatory requirements for T cell activation and the recent recognition of negative as well as positive T cell costimulation mediated by families of receptors originally discovered on natural killer (NK) cells is discussed. The important question of the control of apoptosis in the immune system is discussed, as well as the general question of DNA damage and repair, both nuclear and mitochondrial. A greater understanding of repair mechanisms may be important for remediation. These and other topics covered in this volume reveal the huge gains in knowledge recently acquired but highlight the enormous gaps still waiting to be filled before it can be decided whether the much maligned expression "anti-ageing medicine" will ever acquire respectability. Book jacket.

Table of Contents

Preface	vii
The OCTO and NONA Immune Longitudinal Studies: A Review of 11 years Studies of Swedish very old humans	1	(16)
Anders Wikby
Boo Johansson
Frederick Ferguson
Immune Measures which Predict 9-Year Survival in an Elderly Population Sample	17	(12)
Felicia A. Huppert
Eleanor M. Pinto
Kevin Morgan
MRC CFAS
Carol Brayne
Immunological and Immunogenetic Markers of Successful and Unsuccessful Ageing	29	(18)
Giuseppina Candore
Giuseppina Colonna-Romano
Domenico Lio
Calogero Caruso
Developmental Aspects of the Thymus in Aging	47	(32)
Amiela Globerson
Effective Immunity During Late Life; A Possible Role for the Thymus	79	(14)
Jeffrey Pido-Lopez
Richard Aspinall
Alterations in Signal Transduction in T Lymphocytes and Neutrophils with Ageing	93	(30)
Tamas Fulop
Katsuiku Hirokawa
Gilles Dupuis
Anis Larbi
Graham Pawelec
CD28 Downregulation and Expression of NK-Associated Receptors on T Cells in Aging and Situations of Chronic Activation of the Immune System	123	(10)
Javier G. Casado
Olga DelaRosa
Esther Peralbo
Raquel Tarazona
Rafael Solana
Characterisation of NK Cells in the Elderly	133	(26)
Erminia Mariani
Andrea Facchini
T Cell Ageing and Immune Surveillance	159	(14)
Julie McLeod
A Road to Ruins: An Insight Into Immunosenescence	173	(18)
Sudhir Gupta
Genetic Damage and Ageing T Cells	191	(26)
Owen A. Ross
Martin D. Curran
Derek Middleton
Brian P. McIlhatton
Paul Hyland
Orla Duggan
Kathryn Annett
Christopher Barnett
Yvonne Barnett
Role of DNA-dependent Protein Kinase (DNA-PK), A Protein with Multiple Intracellular Functions, in Cells of the Ageing Immune System	217	(14)
Daniela Frasca
Luisa Guidi
Gino Doria
Linker Histone H1o Gene Expression During Ageing and After the Effect of Histone Deacetylase Inhibitors in Human Diploid Fibroblasts and T Lymphocytes	231	(12)
T.G. Sourlingas
K.E. Sekeri-Pataryas
Zinc and the Immune System of Elderly	243	(18)
Klaus-Helge Ibs
Philip Gabriel
Lothar Rink
Altered Zinc Binding by Metallothioneins in Immune-Neuroendocrine Senescence: A Vicious Circle Between Metallothioneins and Chaperones?	261	(22)
Eugenio Mocchegiani
Robertina Giacconi
Mario Muzzioli
Catia Cipriano
T Cell Exhaustion and Aging: Is Replicative Senescence Relevant?	283	(12)
Rita B. Effros
Cultured T cell Clones as Models for Immunosenescence	295	(14)
Graham Pawelec
Contributor Addresses	309