Age-dependent disregulation of the immune response in humans

Abstract

The review article analyzes literature data on the issues of immune response dysregulation during aging. It has been shown that impairment of innate and adaptive immune response in elderly and senile people under the conditions of spreading the new coronavirus infection is an aggravating factor in the course of the disease and recovery. Neuro-immuno-endocrine changes occurring in the organs of immune system, immunocompetent cells, molecules and receptor formations involved into the arising immune response have been traced. The imbalance of the brain-intestine-microbiota axis is considered in sufficient details, where a significant role is attributed to the changes occurring in hypothalamic-adrenal system under participation of biogenic neurotransmitters and neuromodulators. It is shown that intestinal microbiota may be involved into the neurodegeneration events, due to toxic effects on the brain via the neuro-immuno-endocrine and metabolic pathways. The data are presented, which show that adrenaline, norepinephrine, dopamine and serotonin are involved in the immune response dysregulation, thus making this process similar to the changes that occur during the general adaptation syndrome and stress response of the body. On the other hand, the review notes that chronic stress during aging not only alters the activity of macrophages, lymphocytes and dendritic cells, but also increases the level of proinflammatory cytokines in blood, thereby affecting permeability of the blood-brain barrier. The article emphasizes that with body aging, a neuroendocrine sensory pathway of immune response dysregulation is gradually formed. In this regard, it is noted that the afferent nerve endings and neurons of the vagus, adrenergic and peptidergic nerves are involved into dysfunction of immune system by affecting the processes occurring not only in thymus, but also in the brain. However, it is obvious that the pathodynamic “dysadapting circuit” formed in the higher compartments of nervous system is also involved in dysregulatory immune responses during aging. Hence, the work concludes that the signaling networks of the body's regulatory systems (nervous, immune and endocrine) are closely interconnected throughout the lifetime, but with aging and penetration of antigens into the body, this interaction is easily disrupted at different levels of organization of living matter, thus leading to dysregulation.