Can Artificial Intelligence Solve Immunology’s “Self vs. Not-Self” Debate? – Healthcare Blog

Author: Mike Magee

In 1872, the English mathematician and poet Augustus de Morgan wrote this moving line: “Big fleas have smaller fleas on their backs that bite them, and smaller fleas have smaller fleas on their backs, and so on.”

This truism about species competing for nutrition and reproduction might have come in handy 60 years ago when Napoleon tragically underestimated his enemy's will to survive. It was not stubborn Russians that brought about his demise, but microorganisms.

When he launched his invasion with a staggering force of 615,000 men, 200,000 horses, and 1,372 mobile guns, he appeared unstoppable. But on the way to Moscow (according to Tolstoy's account of this unfortunate event in War and Peace), he lost 130,000 people to Shigella dysentery. Faced with bad weather and Russian troops who refused to participate in the defense of Moscow, Napoleon lost 2/3 of his remaining retreating troops to typhus-borne typhus. Rickettsia prowazekiithe lice that inhabited the corpses were embedded in the putrid clothes of his soldiers.

Under more favorable circumstances, the soldier's immune system becomes their ally. Human bioengineering develops side by side with pathogenic microorganisms determined to make their human hosts smart through chemical means.

Humans rely on innate and adaptive mechanisms to detect and eliminate pathogens. But to do this without harming their own cells, they must be able to distinguish between self and non-self. They must adapt and remember, producing long-lived immune cells and protein receptors that allow them to “catch” and eliminate repeat offenders.

If the system's self-tolerance breaks down, protective processes can go into overdrive, leading to a chronic inflammatory response that destroys healthy tissue and marks the onset of autoimmune disease.

One special situation in which immune tolerance is both normal and important is maternal self-suppression during pregnancy, which allows two independent immune organisms to survive side by side in an intimate relationship.

At four weeks of pregnancy, the tiny developing fetus is already developing cells that will eventually differentiate into immune blood cells. By the third month of pregnancy, these cells travel through blood channels to the liver, spleen, and thymus. Some of them—B cells from the bone marrow and T cells in the thymus—are already functional, but are not required. The uterus is sterile. By 19 weeks, immune cells had also spread to intestinal lymph nodes.

Mother and baby are not genetically identical. However, the mother's immune system does not harm the developing fetal cells. When fetal cells are housed in a sterile uterus, they do not need an active immune system of their own. Also in the fourth or fifth week of development, the fetus has seeded the mother's circulatory system with fetal cells, and these cells are tolerated and not rejected as foreign. Research shows that up to 0.1% of a mother's genes in her adult cells may match those of her child. This is called “microchimerism.”

As long as the child is in the womb, its immune system is asleep, and the mother tolerates her occasional exposure to fetal cells as benign and acceptable. Everything changes at birth.

The newborn is “immunogenically naïve” and is at risk as he/she passes through the bacteria-laden vaginal canal. That’s not to say kids don’t have weapons. Beginning in the 13th week, maternal antibodies cross the placenta and enter the fetus. By the end of the third month of pregnancy, these substances become abundant. The mother's breast milk/colostrum is also rich in antibodies, immunologically active cells, granules and enzymes. These provide immediate, short-lived immune protection and an opportunity to catch up. But over the course of these two months, the supply of rapidly responding neutrophils is limited, and newborns are vulnerable to a range of infections, especially Streptococcus, staphylococcus, Klebsiella hemophilia influenza, and meningococci.

When a baby's immune system kicks in (after two months), every pathogen is brand new. It has no memory until adaptive immunity (in the form of B and T cell lymphocytes) produces specific immunoglobulin antibodies and receptors that can mark future invaders for destruction. That's why pediatricians tell new parents that any fever that develops before two months needs to be checked immediately.

It is fair to say that there is still much to be understood in the field of immunology. But researchers believe further research into fetal immunity could lead to a range of new findings. “Tolerance to fetal allografts” certainly generates considerable academic interest. But many believe that understanding the complex chemical and physiological systems that make this possible could lead to clinical breakthroughs in cancer treatment, management of autoimmune diseases, and avoidance of the degenerative inflammatory diseases that accompany aging.

A growing number of leading research immunologists are challenging the foundations of the discipline's self-identity. Consider these words from a May 2025 issue of Frontiers in Immunology addressing the long-held “self vs. non-self” theory:

“Indeed, part of its obsolescence is a tribute to advances in immunology. As we learn more about microbiome-immune interactions, Epigenetics Being so malleable, the field will undoubtedly continue to change. The fundamental question of how an organism maintains its integrity in a changing microbial, tissue, and signaling environment remains as important as ever, but the answers we seek must match the complexity and dynamism of biological reality. if it means hugging 'The end of dogma,'It also heralds the dawn of more integrated immunology. “

Are humans smart enough to solve all this? Maybe not.

But Anthropic CEO Dario Amodei is a former biomedical researcher who turned to artificial intelligence to allow humans to overcome the fears of Augustus de Morgan. As he said recently, “One of the things I observe most when I work in this field is its incredible complexity. I had this feeling: Man, this is too complicated for humans. We are making progress on all these issues in biology and medicine, but progress is relatively slow. So what drew me to artificial intelligence was this idea: Can we make progress faster? “

Mike Magee, MD, is a medical historian and regular contributor to THCB. he is Code Blue: Inside the U.S. Medical Industrial Complex. (Grove/2020).