The Adaptive Immunity of Microbes

Microbes have a bad – and perhaps unjustified –- reputation.

This poor reputation persists in society for multiple reasons: First, people typically associate the word 'microbe' or 'bacteria' with the bad organisms that make us sick, and not the large number of microbes that routinely help us. Second, microbes are often considered to be simpler or more primitive than their larger, multicellular counterparts such as ourselves.

Why are bacteria considered to be 'simple'?

Often, I think our minds tend to expect size to correlate with complexity.

While I can manage cleaning my small apartment fairly easily, I can confidently say cleaning a bigger apartment or something much larger like a massive hotel would be much more difficult day-to-day. This complexity stems from the increasing number of tasks involved; a busy hotel needs to manage their sanitation team, monitor a large supply inventory that constantly require reordering, issue payroll to workers and deal with issues or special requests from guests.

On the scale of our daily lives, this interaction between size and complexity makes intuitive sense.

PHENOMENAL COSMIC POWERS … Itty-bitty living space
— Genie from Disney's 1992 Aladdin

Complexity can also stem from having to perform the same amount of tasks in a very small space. Consider cellphones, we often laugh when we look back at how big and ridiculous the original cell phones were, but this reduction in size was far from simple. Many advances in technology and complexity were required to accomplish the same things on such a compact scale. And now, the smarter and compact versions of these phones many of us depend on today, are complex due to both size and increasing task capability.

A Qualcomm QCP-2700 (left) circa 1998, and a current production iPhone 5 from 2013, 15 years later. The amount of change is astonishing. Photo credit: via wikipedia.org by Irfan Nasir

A Qualcomm QCP-2700 (left) circa 1998, and a current production iPhone 5 from 2013, 15 years later. The amount of change is astonishing. Photo credit: via wikipedia.org by Irfan Nasir

Microbes are like cell phones; they are complex because they need to put the same essentials in a much smaller package. Often, they do so in pretty remarkable and surprising ways. The obvious example is viruses. Science has difficulty even categorizing viruses as 'living' because they have reduced the core components of life down to their DNA or genetic code, and a protective coat made of proteins.

Can microbe achieve an adaptive immunity?

First off, what is an adaptive immunity? In the interest of time, I will summarize a very complex field in a few sentences. If you are interested, I recommend you check out Science by Adam, a blog with numerous, easy-to-read posts on immunology.

For my purposes, I want you to understand one thing: adaptive immunity is complex. For us, adaptive immunity involves acquiring information from past infections, and teaching our bodies and other cells better ways to combat similar infections in the future. The system depends on a complex network of organs, tissues, cells, and different genes to accomplish this task. Since microbes are single-celled organisms, can microbes like bacteria achieve this same level of protection? Turns out, yes.

Microbes have devised a clever way to achieve this complexity to combat viruses without all these organs and different cell types. Clustered Regularly Interspaced Short Palindromic Repeats or CRISPRs are what allow microbes to remember past infections to protect themselves.

Illustration of the CRISPR system on how the use of interchangeable RNA sequences provides specificity to certain infections. Remember: think of it as an 8-in-1 screwdriver. Simply change the tip and you can now target a different infection. Photo credit: Gabrielle Dowell and Kenny Flynn.

Illustration of the CRISPR system on how the use of interchangeable RNA sequences provides specificity to certain infections. Remember: think of it as an 8-in-1 screwdriver. Simply change the tip and you can now target a different infection. Photo credit: Gabrielle Dowell and Kenny Flynn.

Each “repeat” that is characteristic of this system is separated by short pieces of spacer DNA that are actually leftover from past viral infections. Combined with the CRISPR associated proteins called cas proteins, microbes are able to create a protein complex with interchangeable DNA spacers with specificity to certain viruses. This specificity is exactly what makes the adaptive immune response work in humans; specific T cells roam our bodies and monitor for a specific threat for quick, swift action.

Consider a 8-in-1 screwdriver with interchangeable tips. Instead of having a completely different screwdriver for each application, you simply need to exchange one piece. These cas proteins work the same way. When these cas protein complexes form, different protein complexes have different DNA spacers that could be used.

So, there you have it. Small does not mean simple. In fact, accomplishing the same tasks in a small space can be even more impressive.