IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

STRUCTURE AND PRINCIPLES OF FUNCTIONING OF THE IMMUNE SYSTEM

Immunological Disorders in Aging

Alterations in immune system function begin long before any outward manifestations of bodily Aging. A normal Immune Response and intact Genetic regulation OF immunoreactivity are essential prerequisites for resistance to disease and aging.

Age-related decline in immune function is influenced by both exogenous and endogenous factors, including Changes in the cellular microenvironment (disruption of neurohumoral balance) and alterations within the immune Cells themselves. Many researchers view aging as a state of T-Cell immunodeficiency, wherein age-associated changes in the T-cell population are driven by the age-related involution of the Thymus.

Aging is accompanied by a decrease in the number of T lymphocytes. However, while the Total Cell Count may sometimes remain unchanged, there is an expansion in the proportion of redundant cells, which is linked to diminished activity of the cellular receptor apparatus. Aging is characterized by a more pronounced reduction in the T-suppressor population (CD8+ cells) and a less pronounced decrease in T helpers (CD4+ cells). Furthermore, distinct features emerge within the T-helper populations of elderly individuals, notably a deficiency in memory T cells.

The primary age-related alteration of The Immune System is thymus involution, which begins at Puberty. It is characterized by a progressive loss of cellularity (by old age, thymic mass is reduced by 90%), depletion of the lymphoid cell pool in the cortical areas, and cystic changes in epithelial cells. With advancing age, There is a decline in the output of differentiated T cells, as well as in the Synthesis and Secretion of thymic polypeptide Hormones such as thymosin, thymopoietin, and thymulin. In all cases, the reduction in endocrine activity of the thymus plays a pathogenic role in the age-related dysfunctions of the immune system.

Aging is associated with decreased expression of Histocompatibility Antigens on T lymphocytes, which impairs the recognition of alloantigens and the subsequent transmission of signals required for antigen elimination and antibody production.

However, The impact of involutive processes in the thymus is not restricted to the T-cell branch of Immunity; it also affects the B-cell branch—both through cellular interactions during the immune response and by influencing the GENERATION OF B cells from their Bone Marrow precursors. In certain instances, B-cell immunodeficiency stems from intrinsic defects within the B cells themselves.

Age-related changes in humoral immunity. Aging is significantly associated with the presence of various autoantibodies, particularly anti-nuclear Antibodies. There is also evidence that aging affects The rate of antibody production by activated B cells.

The aging process attenuates the HUMORAL IMMUNE RESPONSE to both autologous and exogenous antigens, a process directly involving various immunoglobulin classes. An immunoglobulin imbalance develops with age. It is well established that aging involves a decrease in Blood IgM concentrations, reflecting a diminished primary humoral response. Conversely, IgG and IgA levels tend to increase. During active infections, the concentration of IgA rises markedly. This immunoglobulin imbalance indicates a decline in antimicrobial defense, which accounts for the heightened susceptibility to infections observed in elderly and senile individuals.

There is evidence of reduced Lysozyme concentration, decreased b-lysin activity, and lower levels of the C3 Complement component in elderly individuals. Changes in the macrophage system during aging are associated with reduced cell migration capacity, a decline in the number of active cells, and a diminished efficiency in engulfing and destroying captured material—in other words, a reduction in the phagocytic and digestive capacities of macrophages.

Advanced age is characterized by a decline not only in antimicrobial immunity, but also in antiviral and antitumor defense, which is directly linked to cell-mediated immune responses involving natural killer cells. During aging, the quantitative content of killer cells changes; it can either increase or decrease. However, their functional activity after the age of 70 generally declines. It is only in centenarians that an increase in NK cell activity is observed once again, as they take over cell-mediated immune responses.

Summarizing the above, the changes in the human immune system that accompany aging are as follows (Butenko H.M., 2003):

✵ beginning from the period of puberty, atrophic processes occur in the thymus, and it is gradually replaced by connective and adipose tissue;

✵ The production of hormones that promote T-lymphocyte generation decreases; on the other hand, substances that inhibit lymphocyte proliferation appear;

✵ the level of IL-7, a cytokine that stimulates the proliferation and differentiation of thymocytes, decreases;

✵ control over the Maintenance of the body's antigenic Homeostasis is impaired;

✵ the capacity for an Immune Response to foreign agents is reduced;

✵ the frequency and severity of autoimmune reactions increase, and the level of circulating immune complexes rises;

✵ the probability of lymphoproliferative disorders—both benign (monoclonal gammopathies) and malignant (Various Forms of leukemias)—increases;

✵ The Diversity of produced antibodies and T-cell receptors diminishes, narrowing their spectrum;

✵ the magnitude and duration of the response decline;

✵ the count of CD4+ T cells and CD19+ B cells in the blood decreases, while the number of CD8+ T cells increases amidst a diminished response to mitogens and elevated levels of circulating IMMUNOGLOBULINS;

✵ the levels of IL-6, TNF-α, and soluble TNF receptor type II increase;

✵ decreased CD4/CD8 ratio along with increased HLA-DR expression;

✵ increased Susceptibility to infectious diseases (infections are detected in 65% of elderly decedents); notably, fever is absent;

✵ age-related immune changes play a role in the Pathogenesis of atherosclerotic vascular damage (the immune system and chronic inflammation trigger endothelial cell dysfunction, whereas alterations in the Lipid Composition of the vascular wall act as a secondary factor).

Finally, Table 8 presents the main relative and absolute values of Blood Leukocytes and major immunoglobulin classes, which constitute the Components of the immunogram in healthy individuals across various age groups.

Class="center">Table 8. Immunogram parameters in healthy individuals of different ages