This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The immune system is central to human health and its impairment or dysfunction can have severe or even fatal consequences. One of the hallmarks of aging is the progressive loss of immune function, exposing older people to increased risk from infectious diseases that would not normally be more than an inconvenience. While many indicators for this decline in immune function have been proposed, only a few have withstood scrutiny and none of these lend themselves to rapid screening. This project will take advantage of a new, high throughput immune monitoring platform developed by the Stanford Center for Immune Monitoring to survey older individuals for signs of immune senescence and to begin to gather data on what factors may correlate with its onset and the rate of decline. Biomarkers that correlate with a poor immune response to flu in elderly people may also predict younger people who are at greater risk. From this study, we will also use a variety of more standard assays and all of these studies will be performed on older adults, aged 60-100 years, who are receiving a standard influenza vaccination. We hope to identify new markers for immune senescence, clues as to how the immune system is affected, and begin the assembly of a database that would rigorously define positive or negative contributors to this phenomenon (such as genetics, physical activity, etc.). To accomplish these goals, we will:1) Compare lymphocyte responses at Days 5-7 and the lymphocyte and serology responses at Day 28 post-immunization following administration of seasonal trivalent inactivated influenza vaccine2) Evaluate changes in cytokine profile in the immune response (CD4, CD8, B cell responses) from Day 0 to Day 5-7 for T-cells and antibody-secreting cells (ASCs)3) Evaluate changes in cytokine profile in the immune response (CD4, CD8, B cell, and serology responses) from Day 0 to Day 28-32 for antibody responses.4) Compare monocyte reactivity to activating stimuli at Days 0 and 5-7 with the lymphocyte and serology responses at Day 28-32 post-immunization following administration of seasonal trivalent inactivatedinfluenza vaccine5) Determine whether any of the immune responses correlate with protection from reported influenza-like illness at the end of the flu season6) Determine the effect of level of physical activity on the generation of immune response to influenza vaccine
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