Chapter 125
Controlling Our Immune System — 2
The total package and distribution of immune system cells has been quantified, as seen in figure 9.1. Dendritic cells, with their unique morphology of branched tentacles, are concentrated in lymph nodes, below our skin and mucosa surfaces, and can identify the enemy by sampling, storing, or processing antigens. Antigens are any substance from outside the body that induces an immune response, such as viruses, bacteria, toxins, or chemicals. Dendritic cells present antigens to T cells (formally called antigen-presenting cells, APCs), which in turn can secrete small proteins called cytokines, and in such a way either activate the T cell response or promote tolerance.
Figure 9.1. The immune cells distribution in our body. Adapted from Ron Sender et al., “The total mass, number, and distribution of immune cells in the human body,” Proceedings of the National Academy of Sciences of the USA 120, no. 44 (October 2023): e2308511120, https://doi.org/10.1073/pnas.2308511120.
Tregs are the principal guardian regulatory cells that can put the brakes on, preempting an autoimmune attack and modulating components of both systems. You can think of them as the opposite of immune checkpoint inhibitors, which take the brakes off cellular immune responses, whereas Tregs can suppress those same kinds of responses. Tregs come to the rescue of a body attacking itself. Even healthy individuals have some autoreactive T cells that circulate in their blood, leading Ruslan Medzhitov and Akiko Iwasaki to propose “Tx cells” that recognize and monitor self-antigens.
Despite the powerful defense our cellular immunity provides, the total population of immune cells accounts for only about 1.2 kg of our bodyweight, with the breakdown by cell type and number shown in the illustration (fig. 9.2). Macrophages, with their large cell size, establish residence in most tissues and account for 10 percent of cells, but disproportionately half of the total mass. Their functional significance to health and disease has been increasingly recognized in recent years, such as their role in the heart, in atherosclerosis, and in inflammatory bowel disease. That is especially the case with microglia, the main macrophage subtype in the central nervous system. Systematic single-cell sequencing of all the different immune cells through the Human Cell Atlas, interactions with cytokines, and with the aging process have markedly improved our understanding of how our immune response operates.