Age- and disease-related innate immunity of human leukocytes ex vivo (original) (raw)

Altered cytokine production in the elderly

Mechanisms of Ageing and Development, 1998

Elderly persons are more susceptible to bacterial and virus infections and neoplasias than young adults. This is related to an impaired immune response. Lymphocytes of the elderly show a decreased proliferation after induction with mitogens. The decreased proliferation is correlated to a decreased release of interleukin (IL)-2 and soluble IL-2 receptor (sIL-2R). However, IL-2R expression on the cell surface is normal. Interferon (IFN)-k as the main T-helper-1 (TH1) cytokine is produced less by lymphocytes of the elderly, whereas the TH2 cytokines IL-4 and IL-10 are produced in higher amounts as compared to stimulated lymphocytes of young donors. The decreased production of IFN-k is correlated to a decreased number of CD45RO +/CD8+ T cells. Therefore in the elderly there seems to be a dysregulation in the TH1/TH2-system which is predominated by TH2-functions. Monocyte function seems to be increased in the elderly. Leukocytes of elderly persons produce higher amounts of IL-1, IL-6, IL-8 and tumor necrosis factor (TNF)-h after induction with lipopolysaccharide (LPS) than leukocytes from young donors. In contrast, in vitro induction of IFN-h by viruses is decreased in the elderly compared to the young. In conclusion, there are cellular defects and dysfunctions in the elderly resulting in an altered immune response.

Immunity to acute virus infections with advanced age

Current Opinion in Virology, 2021

New infections in general, and new viral infections amongst them, represent a serious challenge to an older organism. This review discusses the age-related alterations in responsiveness to infection from the standpoint of virus:host relationship and the host physiological whole-organism and specific immune response to the virus. Changes with age in the innate and adaptive immune system homeostasis and function are reviewed briefly. This is followed by a review of specific alterations and defects in the response of older organisms (chiefly mice and humans) to acute (particularly emerging and re-emerging) viral infections, with a very brief summary of the response to latent persistent infections. Finally, we provide a brief summary of the perspectives for possible interventions to enhance antiviral immunity.

Alterations in immune functions during normal aging and Alzheimer's disease

Psychiatry Research, 1999

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Cytokine production pathway in the elderly

Immunologic Research, 1996

It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. This review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-γ and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-α, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-γ and IL-2 production as well as TNF-β. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.

The immune S ystem in the elderly

Immunologic Research, 1999

Profound and complex changes in thè immune response occur during thè aging process. Immunosenescence is reflected by a sum of disregulations of thè immune system and its interaction with other systems. Many of thè changes would appear to implicate age-related deficiencies of thè immune responses. The term immunosenescence designates therefore a sort of deterioration of thè immune function which is believed to manifest itself in thè increased susceptibility to cancer, autoimmune disease, and infectious disease. Evidence has been accumulating from several studies which suggest an association between immune function and individuai longevity. However, there are observations, expecially in very old healthy people, that several immune functions are unexpectedly well preserved and substantially comparatale to those observed in young subjects. These findings raise thè question of whether thè alterations that can be observed in thè immune parameters of thè elderly are a cause or a result of underlying disease processes. Moreover, studies on centenarians revealed a remodeling of thè immune system rather than a deterioration, suggesting that thè changes observed during immunosenescence do not correspond to immunodeficiency. The underlying mechanisms of these events are however stili unclear. The purpose of thè present review is to assess thè status of research on thè immunobiology of aging. In this first section, we focus attention on thè B celi biology of aging. In clinical practice, thè changes in humoral immune responsiveness and antibody-mediated defense mechanisms could greatly influence thè incidence and outcome of bacterial infections and autoimmune diseases as well as thè response to vaccines.

Dysfunctions of the immune system associated with age

2019

Background: The human immune system consists of innate and adaptive responses. Innate immune response is the first line of the body's defense, while the adaptive response eliminates pathogens in later stages of infection. Cooperation between innate and adaptive immune response is important to effectively eliminate pathogens. An integral part of the aging of the human body is the aging of the immune system, which results in functional disorders directly affecting the deterioration of health. Abnormal functioning of the immune system is a predisposing factor to the occurrence of old-age diseases, as well as reduces the effectiveness of protective vaccination especially recommended to geriatric patients. Material and Methods: The current state of knowledge on age-related immune dysfunctions has been reviewed. The analysis concerned publications in English and Polish language published in the years 2003-2018, which were collected in the PubMed and Google Scholar 12 database. Particular attention was paid to publications presenting the results of research conducted on a group of geriatric people in order to analyze the facts from the research. The publications were searched on the basis of key phrases, among others: the immune system of the elderly, chronic inflammation, innate immunity and adaptive immunity. Results: A review of current knowledge showed the seriousness of the problem of the aging of the immune system. In addition to reducing the efficiency of the immune system, special attention should be paid to chronic inflammation that predisposes to old-age diseases, as well as to reduce the effectiveness of immunization, which is a serious threat. Conclusion: Analyzing the sources of chronic inflammation in the elderly, particular attention was paid to the phenotype of aging cells, changes in the intestinal microflora of the elderly, the role of adipose tissue in the process of inflammation and changes in the levels of steroid hormones. Public awareness of the etiology of the problem is an excellent method of counteracting the negative effects of immunodeficiency. One of the recommendations is physical activity as part of the elimination of adipose tissue capable of securing an infinite number of pro-inflammatory cytokines.

Cellular immune activation in Sardinian middle-aged, older adults and centenarians

Experimental gerontology, 2017

In addition to viral infections, malignant disorders, autoimmune diseases, and allograft rejection episodes, neopterin increases in older people where it is found to be predictive of overall mortality. Thus, the serum concentrations of this biomarker of systemic immune and inflammation activation, were measured in a small cohort of Sardinian middle-aged, older adults and centenarians. There was a significant positive correlation between neopterin concentrations and age with the subjects in the 95-year-old group with the highest values. Notably, the group of centenarians had neopterin values comparable to those of 80- and 90-year-old groups, and significantly lower than that of 95-year-old group. This suggests a decreased monocyte/macrophage-mediated immune activation and an apparently preserved immune status in centenarians.