Understanding the immune system and the causes of its improper functioning

In all likelihood, you have at least heard about the many allergens (such as dust mites, peanuts and wood pollen) that cause allergies. You may also have heard of infections and toxic pollutants that trigger autoimmune diseases. I do not claim that these ideas are completely unfounded, but there is an alternative and much simpler model of the occurrence of immune disorders. For the emergence of such diseases, you do not need to introduce anything new into your body. All that is needed is essentially the elimination of one important element of the immune system, which will lead to the fact that the body will die, engulfed in a firestorm of autoimmune and allergic diseases.

Immunologists came to this conclusion by studying cases from life.

In 1982, immunologists at the Oregon University of medical Sciences in Portland described a case of one infant who died of multiple autoimmune diseases — type one diabetes, thyroiditis (inflammation of the thyroid gland), atopic dermatitis, diarrhea, and a self-destructive immune response to a viral infection. Seventeen other infants of the boy’s relatives suffered the same fate, but none of them were girls. Scientists have suggested that there is a genetic mutation in the girls ‘ X chromosome.

The boys only have one X chromosome, from their mother. Therefore, while girls who have an X chromosome from each parent can always resort to the effective instructions contained in the second X chromosome, boys can rely on only one X chromosome, no matter what defective genes it contains. In all likelihood, the boys in question inherited the gene that precipitated the collapse of the immune system.

Two decades passed before geneticists discovered the culprit. This gene was called FOXP3 (eng. forkhead box protein 3 is a transcription factor of the forkhead family) [21]. When turned on, the FOXP3 gene changes the way white blood cells function, transforming them from peacemakers to aggressors. In the example above, a spontaneous mutation disabled this gene in boys, leaving them unable to contain immune system aggression. They launched a thermonuclear war against infectious agents, which caused serious collateral damage. In addition, the body of these boys attacked even their own tissues. Mystery solved. Case closed. But this conclusion radically changed the current ideas about the immune system.

For decades, immunologists have envisioned a system that prevents attacks on itself by eliminating self-reactive immune cells as well as applying the molecular equivalent of a pass system. Cells that are part of the immune system (“your” cells) show a one — of-a-kind pass (major histocompatibility complex, MHC). The infectious diseases there is no such pass, so patrol catches them easily. However, in some cases, the immune system attacks even cells that have “their” marks. In addition, in the intestines of some people safely inhabited by many microorganisms that do not show any pass, but the immune system still does not notice them. It was obvious that outdated ideas needed to be revised.

Meanwhile, scientists have experimentally caused a number of autoimmune diseases by doing exactly what the FOXP3 gene mutation did — shutting down or limiting the activity of peacemaker cells. It was obvious that white blood cells, which act on “their”, exist in healthy animals; it is a natural component of the functioning of the immune system. Order is maintained not by the destruction of these cells, but by their containment. Diseases do not occur because distraught lymphocytes are able to avoid destruction (this is an outdated idea), but because ineffective or missing suppressor cells can not curb them. The allergic and autoimmune diseases that plague us today stem from an inability to “control the police.”

By the end of the 2000s, a new model was developed. Soon after birth, the body is populated by a wave of autoimmune cells. They provide protection, strengthen antitumor immunity and promote tissue repair. These pioneers of a wave of cells peacekeepers, limiting the autoimmune cells and providing balance. However, maintaining peace in the long term requires more suppressor cells. This auxiliary army appears only after contact with the outside world — with certain parasites and microbes. Such a dependence is indeed an unusual character. This means that our ability to self-regulate, to maintain homeostasis, oddly enough, depends on external stimuli. What a serious structural defect-unless you consider the human body in the proper context.

In all respects, except for size and weight, you are, for the most part, not you at all. The number of commensal bacteria in your gut, weighing up to one and a half kilograms, is ten times the number of your own cells. The collective genome of this community of microorganisms is a hundred times larger than your genome. This community includes representatives of three major branches of life on Earth: bacteria (prokaryotes), yeast (eukaryotes) and archaea (microorganisms that live, among other remote shelters, in deep-sea hydrothermal vents). You are an established ecosystem, a cluster of interdependent forms of life. Scientists call it a superorganism.

Now dependence on” external ” factors makes more sense. How can your genetic ” I “(the” you ” that appeared at the moment when daddy’s sperm fertilized mom’s egg) ignore the voice of the majority? This seemingly absurd error that causes autoimmune diseases also makes a little more sense. Eliminate or change these stimuli — and the immune system, as expected, will lose orientation. These signals direct your immune system and make it more stable.

Unfortunately, this is the story of the last century-perhaps it explains why today the human immune system functions with such impressive violations. We consistently show a lack of tolerance for everything — harmless proteins (allergies), our own tissues (autoimmune diseases), and commensal microflora (intestinal inflammation) – because at the environmental level we did what the FOXP3 mutation did at the genetic level. By changing our internal ecology, we have blocked an extremely important inhibitory tool of the immune system.

The question is: can we replace these incentives? Can I embed the protective factors in the habitat tribe tsimane in their environment? And can I do that without destroying myself and losing the unprecedented level of both quality and life expectancy of developed countries?

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