Immune System Scales Defense Response

close up of pink and white barium sulphate crystal alveoli with macrophage

Biological Strategy

Humans

Sam Stier

Image: Yale Rosen / Flickr / Some rights reserved

Coordinate by Self-Organization

To create and maintain a healthy community of individuals and ecosystems requires that living systems coordinate their activities. Coordination doesn’t necessarily mean that there’s a leader orchestrating what happens. In nature, coordination is usually achieved through self-organization. In a flock of geese flying in a V-formation, for example, there’s no lead goose controlling where all of the others fly. The flock uses this formation because each goose gains energy from air vortices created by the goose in front of it. The lead goose doesn’t gain that benefit, so when it tires, it moves back and another goose takes the front position.

Search this Function

Mammals

Class Mammalia (“breast”): Bats, cats, whales, horses, humans

Mammals make up less than 1% of all animals on earth, but they include some of the most well-known species. We know first-hand some of the characteristics that make mammals unique, like having hair, being able to sweat, and producing milk through mammary glands. Another critical shared feature is a set of highly-specialized teeth. Unlike sharks or alligators, for example, whose teeth are generally all the same size and shape, mammals have differently shaped teeth in different areas of the jaws to target specific foods or foraging strategies.

Search this Living System

Macrophages use communication to scale defense strength to threat

If a house is burning, firemen will try to put the fire out with water. Even though the water itself can damage a house, it’s likely less damaging than the fire. A similar logic pertains to our immune system. Our immune system protects us through physical and chemical means, but in the process, it can also damage our own tissues by attacking our own cells. How does our immune system apply enough defense to take care of an injury or infection, but not so much that it might hurt or even kill us in the process?

When we get injured, our body can become infected with foreign microbes. For example, if you fall on the ground after scraping your knee, microbes can enter your body through the open wound. This is why it’s important to keep wounds clean. If an area becomes infected, the tissue around it swells and certain cells called macrophages rush to the scene to attack the infection.

Macrophages can attack an infection in different ways. For example, some attack with full strength while some attack less intensely. How a macrophage responds depends on several things. First, individual macrophages communicate with one another to determine how many of them are at an infected site. The more macrophages there are, the more they attack at full strength. Also, if the macrophages have fought the microbe before, a higher number of them will attack at full strength. There are always other macrophages nearby that are ready to attack in case the infection suddenly becomes stronger. However, if the wound is small or there are fewer microbes, the macrophages will respond less intensely.

This coordinated attack on infections by macrophages helps to make sure our immune systems don’t over-react, and that the right number of immune cells are working as hard as they need to in any given situation. The dynamic way our immune cells react to threats can give people ideas for designing response guidelines for all sorts of potentially threatening situations, such as how to evacuate buildings in the case of fire or earthquake.

Last Updated May 14, 2020

References

“The dependence of the decision to become highly activated on cell density has some resemblance to bacterial QS, in that the phenotypes of individual cells are determined by information shared by the population. However, an important distinction is that in QS essentially all cells become activated if a threshold concentration of QS molecule is surpassed, whereas here the proportion of highly activated cells increases with density. Therefore, because only a fraction of the cells become licensed to reach a state of high activation, the population exhibits an analog response rather than a digital one. To distinguish these two phenomena, we refer to the macrophage behavior as quorum licensing…” (Muldoon et al. 2020: 4)

“Whatever the underlying mechanisms are for maintaining longterm activation propensity, a strategy that enables cells to calibrate their response to future threats by integrating their experience of the surroundings over time (including information about whether other cells have been recruited to that site) could provide functional utility.” (Muldoon et al. 2020: 11)

“Another consequence would be to limit potent inflammation to local environments. In the scenario posed above—a wound experiencing an infection—some DAMPs could travel to sites that are remote from the wound, even if the microbes are limited to the wound site. QL could act to limit the most potent macrophage-mediated responses to sites characterized by both the presence of DAMPs and the local accumulation of macrophages, nonlinearly driving local cytokine production. If macrophage recruitment could be coupled to activation in this way, then QL would enhance the specificity of this potent but potentially harmful facet of innate immune function.” (Muldoon et al. 2020: 11)

Journal article

Macrophages employ quorum licensing to regulate collective activation

Nature communications | Muldoon, J.J., Chuang, Y., Bagheri, N. and Leonard, J.N.

embedly preview

AskNature