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The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

The present book intends to provide an update on immunosenescence and how deficiencies in the immune system contribute to a higher susceptibility to infections, decline in organ function, reduced vaccination responses, age-related disease and the ageing process itself, negatively affecting longevity. Our focus is on the main changes in immune system cells and their products occurring during the ageing process and the possible consequences for health and disease. This includes: discussion of the modulatory and/or suppressive mechanisms associated with the alterations in T regulatory cells, B regulatory cells and Myeloid Derived Suppressor cells; changes in the immune system observed in chronic neurodegenerative diseases, cancer, lung disease and frailty will also be discussed. Most importantly we provide recent literature information about possible interventions (focusing on physical activity) that could alleviate the negative effects of immunosenescence. The Ageing Immune System and Health is a comprehensive guide on the field intended to all physicians, researchers, professors and students interested on relationship between immune system, ageing and health.

The world population presents an increased percentage of individuals over 65 years old and the fastest growing subgroup is over 85 years old. The increase in life expectancy observed in the last century has not been synonymous with extra years lived in good health (disability-free years). Population studies have shown that as individuals age, they can present a great heterogeneity of ability and health. Therefore, aging has been associated for some individuals with disabilities and hospitalizations. Deaths related to infectious pathogens are increased in the aging population mainly due to pneumonia and influenza whereas Cytomegalovirus, Epstein-Barr virus, among other viruses seem to contribute to the low-grade inflammatory process observed (inflammaging). Aging is a complex and multifactorial process in which functions of the organism are adjusted (remodelled) in order to deal with damaging events during life. One of the most important changes in aging individuals occurs in the immune system (innate and adaptive responses) with consequences such as poor response to new infections and vaccinations; increased susceptibility to cancer development and autoimmune diseases; frailty, and organ dysfunction. In addition, it has been proposed that immunosenescence not only reflects the aging of the organism but also contributes to this process. Bone marrow presents decreased hematopoiesis, the thymus undergoes involution and lymphoid organs (lymph nodes, spleen) also present reduced functionality. Therefore, cells derived, matured, or residing in these tissues decline in number and function. These changes have been identified in experimental models, in vitro conditions, peripheral blood, and biopsies via biomarkers such as cell phenotype, stimulus-induced proliferation, cytokines and antibodies levels. Telomere length and telomerase activity also decline in bone marrow-derived and peripheral blood cells and have been shown to play a role in immunosenescence. More recently, the investigation of short non-coding RNA molecules (microRNAs; miRNAs) pointed to this system as a possible control of aging-related mechanisms. Data obtained on these markers for aging individuals could lead to the generation of a marker panel for pathology prediction, to indicate interventions, and to evaluate the efficacy of interventions. Interventions such as nutrition supplements, exercise, vaccination (different dose, concentration of antigen, adjuvants) have been proposed to circumvent age-related diseases. Considering the heterogeneity in the aging process, further investigation is vital before the indication of interventions for aging individuals. As the extension of life expectancy is a reality, it is a challenge to understand how the aging population copes with the remodelling of the organism and how interventions could provide longevity in good health.

Abstract: Costimulatory molecules, including 4-1BB, CTLA-4, and B7, play a critical role in the activation, sustenance, and regulation of T cell immune responses. Manipulation of these pathways holds promise for the development of therapies for cancer and autoimmunity. Anti-4-1BB monoclonal antibody (mAb) has been demonstrated to boost anti-tumor immunity in animal models. Using a model of tumor-specific CD8 T cell adoptive immunotherapy, we demonstrate that anti-4-1BB mAb can mediate the rejection of large established tumors in the absence of CD4 T cell help. Anti-4-1BB mAb increases populations of tumor-specific CD8 T cells in peripheral blood by reduction of activation-induced cell death, but not increased T cell proliferation. The use of anti-CTLA-4 mAb has also been shown to enhance anti-tumor immunity. Here we employ two novel "humanized" mouse models to screen anti-human CTLA-4 mAb for translation to human cancer therapy. Using the hu-PBL-SCID model of Epstein-Barr virus (EBV)-associated lymphoproliferative disease, we show that anti-human CTLA-4 mAb promotes the in vivo expansion of human CD8 and CD4 T cells, and the generation of antigen specific CD8 T cell responses to EBV lymphoma. This correlates with reduced levels of the oncogenic EBV protein LMP-1, and increased survival in these mice. We also characterize the creation of a knock-in mouse model in which mouse T cells express the human CTLA-4 molecule. Preliminary testing in this mouse model supports the use of this model to screen anti-human CTLA-4 mAb for clinical use. Understanding the role of B7/CD28/CTLA-4 interaction in immune activation and tolerance in autoimmune disease is fundamental to successful intervention targeted at costimulatory molecules. We describe the spontaneous development of whole-body alopecia, lymphadenopathy, and skin disease in mice lacking B7 molecules. This disease is mediated by autoimmune CD4 T cells, which induce multi-organ inflammation when transferred to mice expressing B7 molecules. This disease may result from impaired development of CD4+CD25+ regulatory T cells (Treg) in B7-deficient mice. Since provision of Treg can abrogate the multi-organ inflammation despite lack of B7 molecules on the auto-pathogenic T cells, interaction between CTLA-4 on Treg and B7-1/2 on effector T cells is not essential for Treg function.