Chapter 124
Controlling Our Immune System — 1
We’ve discussed ways that we can empower our immune response to meet all kinds of threats to our health span. Though not generally appreciated, the inverse of that—stopping our bodies from attacking themselves—is one of the most important simultaneous advances in life science. About eighty different autoimmune diseases affect more than 10 percent of the population. They include rheumatoid arthritis, Crohn’s disease, and lupus; all are currently treated with lifelong, broad immunosuppressive drugs that usually do not adequately control the conditions. These treatments pose risk of serious infections and, moreover, loss of therapeutic efficacy due to the immune system building resistance to attempts to control it. Our immune system is, after all, evolving.
Just like the breakthrough for obesity with GLP-1 drugs that took many decades, early attempts to achieve control over our immune system began in the 1950s. They all basically failed. Only now are we starting to see remarkable results in conditions like systemic lupus erythematosus, type 1 diabetes, and rheumatoid arthritis. By reprogramming the immune response, multiple strategies are being pursued to make our immune system more tolerant of what appears threatening to it. (The word tolerant is key since these approaches are known as tolerogenic.) This could, and really should, lead to prevention or definitive treatment for these conditions—even a cure.
This bold goal is realistic due to dramatic improvements in our understanding of the complexity of our immune system. It’s one of the most complex systems in our body, if not the most complex. For an in-depth and highly accessible review of its workings, I recommend Phillip Dettmer’s book Immune. For now, here is a primer.
BIOLOGY OF THE IMMUNE SYSTEM
In one drop of blood, we have about 400,000 immune cells and 13 trillion antibodies, admixed with approximately 250 million red blood cells and 15 million platelets. The magnitude of immune cells and antibodies conveys the priority that drop of blood and our whole body puts on the defense against all sorts of insults and attacks. The first line of defense is the innate system, able to rapidly attack and reliably distinguish our cells (“self”) from foreign invaders (“other”). The innate system also gathers intel and determines whether the second line of defense, the system that adapts to unfamiliar foes, needs to be activated. The innate system’s epithelial cells, such as our nasal mucosa, release interferons when exposed to a respiratory virus. This system also includes a variety of nonspecialized types of white blood cells, including macrophages, neutrophils, dendritic cells, monocytes, mast cells, basophils, eosinophils, and natural killer cells. Macrophages are present in every organ of the body. Natural killer (NK) cells, protecting us from harmful invader pathogens, were first described fifty years ago and are now being tapped as a strategy for cancer immunotherapy.
In contrast, the adaptive system is specialized beyond merely distinguishing between self and other. It takes longer to respond, with a line of B cells (B from bone marrow) and plasma cells that manufacture antibodies at whatever the needed scale, and many types of T cells (T from thymus) that are helpers (CD4+), regulators (Tregs), or cytotoxic cell-killers (CD8+). Both B and T cells have memory lineages that have an exquisite ability to recognize invaders they have seen before, even long, long before in the life of that individual. Untrained B cells and T cells are called “naive,” because they are immature, haven’t seen their target antigen, and aren’t yet activated. But when these cells have been trained to remember invaders, they are called memory B cells and T cells. While antibody and cell-mediated immunity are often discussed separately, they are inextricably linked. There’s intense crosstalk between the many different types of cells and all parts of the innate and adaptive immune systems.