Daniel asked: How does the immune system differentiate between the natural microbiota and pathogenic bacteria? Providing that all bacteria have a cell wall that the secreted lysozyme can degrade, for instance. If so, how is this differentiation possible?

Hello Daniel,

First of all, I would like to mention that the question you asked is still an ongoing scientific investigation. The answers to date have been only partial, and it may very well be that in the future new information will be discovered.

The ability of the immune system to differentiate between “self” and “non-self” is one of the main fundamentals of its job - to protect the body without harming it. The development of the immune system, which begins during fetal development and continues into adulthood, coexists along with the regulatory mechanisms in charge of preventing the system from harming all that is “self”. Failure of these regulatory systems may cause a group of severe illnesses, termed “autoimmune diseases” – diseases in which the body attacks itself.     

In recent years, a lot of information has been discovered regarding our intestinal bacteria. Among other things, we have discovered that there is a huge and diverse population of bacteria that reside regularly in our intestine, and we call them “microbiota”. These bacteria are part of our body and are of great importance to our metabolism, since they process materials for us that we cannot manage ourselves. In addition, it was found that these bacteria are important for the development of the immune system itself. Lab mice that do not have intestinal bacteria at all show an immune system that is not as developed as mice raised in normal conditions.

תמונת מיקרוסקופ אלקטרוני של תרבית חיידקי אי-קולי, אחד מזני החיידקים השונים במעי, קרדיט: Rocky Mountain Laboratories
E. coli culture under an electron microscope | Photograph by: Rocky Mountain Laboratories

If you have read everything until here, I hope you are already beginning to understand one of the answers to your question: our intestinal bacteria evolve in parallel to our immune system, and therefore it does not recognize them as non-self. As far as the immune system is concerned, they are an inseparable part of the body. This theory is termed “theory of immune tolerance” – namely, the cells of the immune system “tolerate” the existence of the microbiota and do not recognize it as a foreign entity, so it is not attacked.

Another theory that was raised in the last few years discusses spatial separation. There are certain cells in the intestine that secrete a mucus layer with a special complex structure, which creates a barrier between the cells of the body and the microbiota residing in the intestinal space. Current research claims that this is actually how the bacteria manage to not come in direct contact with the cells of the body. In contrast, when pathogenic bacteria such as Salmonella or Listeria invade the intestine, they will attempt to penetrate the protective mucus layer and attack the epithelial cells underneath it. This sort of invasion will summon the immune cells under the epithelial layer to act against the bacteria and defeat the infection.

Therefore, there are a number of theories describing the mechanism that causes our body to ignore a wide population of bacteria that reside peacefully in our intestine, but there is still no clear-cut answer to your question. Currently, research is still working at solving this complex question.

Boomerang – Question Back at You
In what other organs is there a bacteria population that lives in symbiosis with the human body?


Biana Bernshtein
Department of Immunology
Weizmann Institute of Science

Article translated from Hebrew by Elee Shimshoni, PhD student at the Weizmann Institute of Science.
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1 comment

  • Jeffrey Serio

    Answer to the boomerang question?

    You never put the answer to what other organs symbiotic bacteria live. What is the answer