Age Impacts the Local Immune Response to Tuberculin Skin Challenge in Mycobacterium Bovis BCG-vaccinated Baboons

2020 ◽  
Author(s):  
Julia Marianna Scordo ◽  
Tucker J. Piergallini ◽  
Nicole D Reuter ◽  
Colwyn A. Headley ◽  
Vida L. Hodara ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Peripheral Blood ◽  
The Elderly ◽  
Short Term ◽  
Post Vaccination ◽  
Age Related ◽  
Age Related Changes

Abstract Background - Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. To improve health outcomes in our aged population, we must study vaccine responses in the tissue. Here we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test (TST) in adult and aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short-term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In parallel, we determined BCG-induced responses in the peripheral blood of vaccinated animals. Results - In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. Phenotypic analysis of aged peripheral blood cells found several age-related changes in immune cell populations, independent of BCG vaccination, and no impairment in functional responses. Moreover, aged peripheral blood mononuclear cells had increased migration in vitro, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. Conclusions - These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.

scholarly journals Local immune responses to tuberculin skin challenge in Mycobacterium bovis BCG-vaccinated baboons: a pilot study of younger and older animals

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Julia M. Scordo ◽  
Tucker J. Piergallini ◽  
Nicole Reuter ◽  
Colwyn A. Headley ◽  
Vida L. Hodara ◽  
...  
Keyword(s):  
Pilot Study ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Peripheral Blood ◽  
The Elderly ◽  
Delayed Type Hypersensitivity ◽  
Short Term ◽  
Post Vaccination

AbstractIndividuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. In this pilot study, we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test in two adult and two aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. In vitro, aged peripheral blood mononuclear cells had increased migration and functional responses to antigen-specific stimulation, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.

Understanding and Managing Sleep Difficulties in the Elderly

2000 ◽  
Vol 13 (4) ◽  
pp. 316-326 ◽  
Author(s):  
Martin D. Higbee ◽  
Cecilia M. Plaza ◽  
Joy Dunkelbarger-Reed
Keyword(s):  
The Elderly ◽  
Short Term ◽  
Geriatric Population ◽  
New Novel ◽  
Common Complaint ◽  
Age Related ◽  
Sleep Physiology ◽  
Pharmacologic Agents ◽  
Sleep Difficulties ◽  
Age Related Changes

Insomnia is a common complaint in the geriatric population with studies indicating that 23-34% of elderly report symptoms of insomnia. Age-related changes in sleep physiology, diseases common in the elderly, and drug therapies common in the treatment of these diseases may result in difficulties with sleep. Managing these complaints requires a thorough evaluation to determine the etiology of insomnia since it is a symptom and not a disease. Additionally, when treating insomnia, non-pharmacologic issues need consideration before initiating drug therapy. A variety of pharmacologic agents are available to treat insomnia short term. Recently, two new novel agents have been added to the armamentarium of drugs that have some advantages over older, traditional agents.

scholarly journals Rescuing Immunosenescence via Non-Specific Vaccination

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 231-239
Author(s):  
Alexander I. Mosa
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Short Review ◽  
Functional Markers ◽  
Healthy Life ◽  
Related Disease ◽  
Age Related ◽  
Population Vulnerability ◽  
Mechanistic Basis ◽  
Promising Avenue

Discrepancies in lifespan and healthy-life span are predisposing populations to an increasing burden of age-related disease. Accumulating evidence implicates aging of the immune system, termed immunosenescence, in the pathogenesis of multiple age-related diseases. Moreover, immune dysregulation in the elderly increases vulnerability to infection and dampens pathogen-specific immune responses following vaccination. The health challenges manifesting from these age related deficits have been dramatically exemplified by the current SARS-CoV-2 pandemic. Approaches to either attenuate or reverse functional markers of immunosenescence are therefore urgently needed. Recent evidence suggests systemic immunomodulation via non-specific vaccination with live-attenuated vaccines may be a promising avenue to at least reduce aged population vulnerability to viral infection. This short review describes current understanding of immunosenescence, the historical and mechanistic basis of vaccine-mediated immunomodulation, and the outstanding questions and challenges required for broad adoption.

scholarly journals Mitral valve repair versus replacement in the elderly: Short-term and long-term outcomes

2014 ◽  
Vol 148 (4) ◽  
pp. 1400-1406 ◽  
Author(s):  
Puja Gaur ◽  
Tsuyoshi Kaneko ◽  
Siobhan McGurk ◽  
James D. Rawn ◽  
Ann Maloney ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Repair ◽  
The Elderly ◽  
Valve Repair ◽  
Long Term Outcomes ◽  
Short Term

scholarly journals Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

Circulation ◽  
1993 ◽  
Vol 88 (3) ◽  
pp. 1205-1214 ◽  
Author(s):  
P Golino ◽  
G Ambrosio ◽  
M Ragni ◽  
I Pascucci ◽  
M Triggiani ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activating Factor ◽  
Short Term

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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