Unlocking the Mysteries of Immunity in an Ageing Population

In the elderly, there is a higher incidence of tuberculosis, pneumonia, urinary tract infections, and septicemia (bacterial infections in the bloodstream). Infections such as influenza, rhinovirus, and cytomegalovirus (CMV) are also more frequent, leading to increased sickness and death. These trends are linked to immunosenescence and other related factors.

As people age, their immune system weakens, known as immunosenescence. T-cell function and antibody effectiveness decline, reducing response to vaccines. Changes in neural and hormonal systems also affect immune function. This leads to more infections, higher morbidity and mortality rates, and increased risk of cancer.

As people age, fewer progenitor cells are produced in the bone marrow and thymus, crucial for immune cell production. The thymus starts to shrink after puberty, reducing its output of mature T cells. In older adults, T cells show increased expression of Fas and FasL proteins, including soluble FasL in the bloodstream. This may contribute to higher rates of activation-induced cell death and apoptosis, leading to lower lymphocyte counts observed in the elderly.

Macrophages, neutrophils, and NK cells are key parts of the innate immune system, active from birth throughout life, though they undergo some changes with age. Neutrophils in older individuals may develop phagocytic defects.

Phagocytic defects refer to impairments in the ability of cells such as neutrophils to engulf and digest pathogens or foreign particles effectively. This process, known as phagocytosis, is crucial for the immune system to eliminate microbes and debris from the body. When neutrophils have phagocytic defects, they are less capable of efficiently clearing pathogens like Staphylococcus aureus, increasing susceptibility to infections. This phenomenon is particularly notable in aged individuals, where such defects can contribute to compromised immune responses and higher vulnerability to certain microbial infections.

In older individuals, NK cell numbers and function remain mostly intact, although levels of certain cytokines may decrease. Cytokines are signalling molecules produced by immune cells. They regulate inflammation, coordinate immune responses, and facilitate communication between cells to combat infections and maintain overall immune function.

As individuals age, significant changes occur in their immune system, particularly in T cell populations. There is a notable increase in memory T cells but a decrease in naïve T cells. This shift suggests that while the body retains a memory of past infections, its ability to mount robust responses to new pathogens or vaccines may diminish. Furthermore, the overall numbers of T cells, including both CD4+ and CD8+ subsets, decline with age. This reduction in T cell diversity and quantity can lead to decreased immune function and heightened vulnerability to infections. These age-related changes in the immune system, characterized by altered T cell dynamics, underscore the importance of understanding immune ageing to develop strategies that can bolster immunity in older adults and mitigate age-related susceptibility to diseases.

As people age, the diversity of T cell receptors decreases. This reduction is more prominent in CD8+ T cells compared to CD4+ T cells. Additionally, T-cell responses to both mitogens and antigens diminish with age. This decline is caused by various internal and external factors, such as defects in presenting antigens, signalling pathways, and cytokine production.

Genes involved in immune response, particularly HLA genes, play a crucial role in enabling the immune system to effectively combat infections. Various HLA haplotypes can influence mortality rates and lifespan. Immunosenescence is further complicated by ageing of the endocrine and nervous systems. This includes not only declining immune function but also changes associated with ageing of neural and endocrine systems, as well as their interactions.

The result of these factors is a compromised immune system in elderly individuals. This manifests as a reduced ability to fight microbial infections effectively, leading to higher susceptibility to diseases such as tuberculosis, pneumonia, urinary tract infections, septicemia, influenza, rhinovirus, and cytomegalovirus. Additionally, the ageing of the neural and endocrine systems further contributes to immune system decline, impacting overall health and potentially increasing mortality rates among the elderly.

 Source: Roit Immunology