Age-related aging of the immune system (6)

Between the death of immune cells and the activation of cytokine synthesis

Immuno senescence in aging: between immune cells depletion and cytokines up-regulation Maria Teresa Ventura et al., Clinical and Molecular Allergy, 2017.

Translated by Evgenia Ryabtseva
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Innate immune system

Changes in the innate immune response are of great importance, and a number of interrelated studies have identified a new direction in the field of immunogerontology, beginning with the weakening of the barrier function of the epithelial layer of the skin and mucous membrane of the digestive tract and respiratory system, followed by changes in the local ratio of immunoglobulins. Moreover, even some physiological events, such as a decrease in thymus mass, confirm the hypothesis that the immune system plays an important role in the phenomenon of aging. It also substantiates the theory explaining the development of a number of immunological diseases characteristic of old age, such as autoimmune diseases, malignant tumors and infections. However, the high frequency of infectious events in old age may be secondary to changes in the phagocytic system.

As for the skin, the aging of the immune system is manifested by a violation of all structures, accompanied by the extinction of the barrier function, a decrease in the number and volume of hair, a decrease in the number of sebaceous glands, loss of skin elasticity, a violation of the immunological protection of the skin.

Dendritic cells responsible for the primary recognition of pathogens entering the skin demonstrate mitochondrial dysfunction, which worsens their protective properties. The ability to absorb antigens and apoptotic function are particularly severely impaired.

Data were also obtained according to which plasmocytoid dendritic cells of elderly people are characterized by a decrease in the ability to induce CD4+ and CD8+ proliferation and stimulate their secretion of interferon-gamma.

Macrophages

Macrophages capable of producing proinflammatory cytokines (tumor necrosis factor-alpha, interleukins-1, -6, -8) perform the function of processing and presenting antigens to T cells. Researchers have described a decrease in the number of macrophage precursors In the process of physiological aging, while the number of monocytes remains unchanged. Shortening of telomeres in old age leads to a decrease in the production of granulocyte colony-stimulating factor, as well as cytokines, such as tumor necrosis factor-alpha and interleukin-6.

Against the background of a decrease in phagocytic function, the preservation of chemotaxis is observed, especially in the presence of certain factors, such as stimulators of the complement fragment C5a (in the presence of this factor, the production of lymphocytic chemotactic factor decreases, as does chemotaxis). In this case, the inhibitory mechanism seems to be associated with prostaglandins, which are produced in large quantities during aging, in which they have an inhibitory effect. Reduced production of lymphocytic chemotactic factor may be associated with a low proportion of lymphocytes involved in the synthesis of this cytokine.

Neutrophils

The number of neutrophils in the elderly is preserved, however, the expression of the CD16 receptor Fc–gamma molecule on their surface is reduced. The consequence of this is a simultaneous age-related decrease in superoxide production, mediated by Fc receptors, and phagocytosis. Apparently, the extinction of the effector response of Fc receptors is the most important component of neutrophil dysfunction in the elderly.

The reduced neutrophil response of elderly people to Staphylococcus aureus (Streptococcus Aureus) is of fundamental importance for clinical practice, as it is accompanied by increased susceptibility to lung infections. At the same time, the migration of neutrophils to the lungs in old mice is reduced, which increases the risk of lung infections and their recurrence.

In addition, an age-related change in the mechanism of pathogen-mediated destruction of extracellular neutrophil traps has recently been described, which confirms the reasons for the increased risk of infectious diseases in the elderly.

Natural killers

The high incidence of immunoproliferative diseases in the elderly indicates that in old age, an important mechanism of immunological surveillance, such as the activity of natural killers, may develop insufficiency. In 1986, the use of "slow" targets, such as a hepatocarcinoma cell line, allowed for an effective assessment of the functions of natural killers and demonstrated a significant decrease in spontaneous cytotoxic activity. The results of recent studies have shown that high cytotoxicity of natural killers is associated with longevity and good health, while a decrease in the functions of natural killers is associated with increased infection and activation of the mechanisms of atherosclerosis and neurodegenerative diseases and, accordingly, with increased morbidity and mortality. Moreover, during the process of cell lysis, natural killers can release cytokines that stimulate apoptosis of target cells. In the process of physiological aging, the level of interleukin-2 lymphokine, which is important for the activation of lymphocytes, as well as the destruction of natural killer cell lines, decreases. This contributes to the disruption of immune function even in the presence of a normal number of natural killers.

In particular, in the process of physiological aging, there is a redistribution of subpopulations of natural killers with a decrease in the number of CD56 cells with a high density of CD56 surface antigens. At the same time, there is an increase in the number of CD56–CD16 natural killers. This leads to a decrease in the secretion of interferon in the elderly compared to the secretion of this cytokine in young people. In addition, in the process of physiological aging, there is a decrease in the expression of activation receptors, especially those associated with NKp30 and NKp46 receptors [66].

Considering that due to the production of cytokines and chemokines, natural killers are involved both in the destruction of tumor and virus-infected cells, and in innate and adaptive immunological regulation, it is very easy to imagine the possible consequences of changing the function of this population in the process of physiological aging.

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