Warzone or Ecosystem? - Rethinking the Immune System

​by Joshua Pirl '19

​The immune system is typically thought of as a military-style force, defending our body in a never-ending battle. Its opponent? Sneaky microbes that evolve nasty ways of evading detection and setting up shop within us. So, when it was discovered that between the cells lining our guts and the trillions of microbial cells that inhabit them lies a largely uninhabited layer of mucus, war emerged as the dominant scientific metaphor. It was deemed the ‘neutral zone’, the ‘front line of battle’, or the ‘demilitarized zone.’ Bacterial toxins, antibodies, and anti-microbial peptides suddenly became ‘short-range missiles’ shot at the other side to keep them at bay, and cells that ventured out into the mucosa were ‘gathering intel’ on the enemy, cold war-style.

​However, when microbiologists and immunologists thought about this, it didn’t seem to make much sense. When multicellular organisms first evolved, we were the new kids on the block. It was a world run by microbes, and we played by their rules. Given this, it was logical for us to develop ways of working with them to survive, instead of creating weaponry to clear them out. It made sense to listen to bacteria so they could tell us what food was in the area, and to use their microbial byproducts as sources of energy to help us survive. Instead of evolving ways to kill microbes, we evolved ways to manage the presence of the right ones.

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​Ed Yong, science writer and author of the best-selling book, I Contain Multitudes, likes to compare the microbiome to a nature reserve, with the immune system as the park ranger. We tend to the species that live within the fence of our reserve, and if anything tries to breach the fence, we use force to control it. We establish a nice home where different microbial species can live together, filling different niches. If an invasive species enters, we remove it, if a predator becomes too dominant, we cull its numbers, and if someone tries to leap the fence, we stop them. There is very simple evidence for this view; animals raised in labs develop strikingly similar microbiome compositions to their relatives in the wild, despite growing up in radically different environments. Interactions between us and the microbes that live within us are therefore specifically evolved and are fundamentally important to our existence.

​Now, if we look at the ‘demilitarized zone’ of the gut through a new lens, the focus changes. This mucosal layer becomes the fence that our immune cells survey to ensure the ecosystem is alive and functioning well. They enter through the fence regularly to sample the population, and if there is an imbalance, they right the ship. There is even some preliminary evidence to suggest that the mucus in our guts is designed to support quadrillions of viruses that target bacteria; aka our immune system might contract out some of its park ranger work to these viruses, paying them with a mucus-y room and board.
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​All of this points to a radically different view of the immune system, one that is trained to kill, but only as a last resort, and to a radically different view of our microbes, not as begrudging neighbors, but as an essential part of our bodies.

Citations:

1. Multi-layered regulation of intestinal antimicrobial defense. Vaishava et al. Cell and Molecular Life Sciences. 2008. https://link.springer.com/article/10.1007%2Fs00018-008-8182-3
2. Rethinking the role of immunity: lessons from Hydra. Bosch, Thomas C.G. Trends in Immunology. 2014. http://www.sciencedirect.com/science/article/pii/S147149061400129X
3. Yong, Ed. I Contain Multitudes. Penguin UK. London. 2016
   
4. Microbiome: The bacterial tightrope. Bourzac, Katherine. Nature. 2014. http://www.nature.com/nature/journal/v516/n7529_supp/full/516S14a.html
   
5. Perkins, Susan. Meet Your Microbiome. American Museum of Natural History.  
   

​              http://www.amnh.org/explore/science-topics/health-and-our-microbiome/meet-your-microbiome