Cells at Work! Provides a Hilarious and Surprisingly Accurate Review of the Immune System

Cells at Work! (Hataraku Saibou) was first released as a manga in Japan in 2015, and it was translated into English by the manga’s writer, Akane Shimizu, the next year. It was produced as an anime in 2018. Twelve episodes are currently available on multiple streaming sites, and a second season has been announced for January 2021. A trailer for a related anime, Cells at Work: Code Black, has just been released and is also expected in January.

Our heroine, Red Blood Cell, with her rescuer, White Blood Cell, on the cover of the first manga volume

Cells at Work! features cheerful and enthusiastic blood cells working in the blood stream of a human body that looks like a Lego-block construction of an enormous city. The main protagonists are Red Blood Cell (AE3803), a perky young woman dressed in blue shorts and a red jacket (reversible, of course), and White Blood Cell (#1146), a heroic young man in white fatigues and a baseball cap. They run into each other frequently, usually when the body they occupy is being attacked by various dangers, like pneumococcal bacteria and influenza virus.

There are, of course, no episodes that deal with the novel coronavirus, but there is plenty of information that can usefully be applied to current events, providing a surprisingly accurate review of the workings of the immune system. As a retired doctor, perhaps I shouldn’t be so amused by anthropomorphic blood cells, but I find the show reasonably informative and up to date. Some of it is based on research that hadn’t been done yet when I trained. This wonderful combination of high school biology and shonen adventure could only come from Japan.

Our heroine, Red Blood Cell, is almost annoyingly cute. Her job, which she performs in the over-enthusiastic way of many working anime women, is to deliver gas canisters or baskets of food to specific locations. But she is always getting lost and running into danger. She is rescued by our hero, White Blood Cell, who can read a map and fight off bad guys. He is the type of white blood cell scientists call a neutrophil, and his job is to kill foreign invaders. He recognizes some on sight, but for others he needs to use his “receptor,” which pops out of his hat when an “antigen” is detected. He kills the invading antigens by stabbing them with a knife, an amusingly bloody process. The shonen tropes of danger and rescue work well in this setting, taking the war metaphors that medicine has been using to describe disease for ages to new levels of silliness.

The two are supported by an ever-growing cast of specialized blood cells, all of which actually exist in the blood stream, though medical journals have given a few of them more scientific-sounding names. There are adorable groups of platelets who look like elementary school children, holding hands to block off compromised blood vessels. There are representations of the many other types of white blood cells that make up the immune system, including antibody-making B Cells, Mast Cells, and Helper T Cells (known as CD-4 cells in the AIDS literature). My personal favorites are the squads of Killer T Cells (or CD-8 cells), which march around in army fatigues and baseball caps labeled KILLER, looking incredibly macho. In their midst, there is always one guy whose hat says MEMORY. It’s his job to remember past pathogens and alert the squad if they reappear. We will return to him later.

All of the blood cells have different faces and distinct personalities. Some of them even have angst-filled backstories from when they were young cells in the thymus or bone marrow, which is, in fact, where blood cells are produced. Watching the Naïve Killer T Cells learn to differentiate good cells from pathogens in a maze-like training ground is pretty hilarious. It’s even funnier that the smart one with glasses grows up to differentiate into a Helper T Cell, who later sits in the research and command office from which he identifies and organizes the response to various invasions.

The non-blood cells (somatic cells) all look the same, though that may be because we only see the cells lining the blood vessels. They wear T-shirts that say CELL and hang around with identical vacuous expressions, unless they are infected, in which case they look like zombies. They live in sterile apartment blocks, working on computers to slowly produce clones of themselves, unless they have been suborned into becoming cancer cells, in which case they produce improper clones much too quickly. They all fear the Killer T Cells—rightly, because one of the jobs of actual Killer T Cells is to dispose of body cells that have become infected, cancerous, or useless.

In the fifth episode, “Cedar Pollen Allergy,” we see how the immune system can overreact to a threat. This is vastly over-simplified, of course, but still more detailed than the average American high school graduate seems to understand. In that episode, after fighting a large, yellow blob, White Blood Cell takes a bite out of it, in order to identify it as Cedar Pollen. (In real life, we are told in a side bar, neutrophils actually work by engulfing invaders, a process known as phagocytosis.) This is how things are supposed to work.

But, when Memory Cell finds out the invaders are Cedar Pollen, he becomes alarmed because of an old prophecy of disaster, and he activates the entire immune system. B Cell shows up and starts squirting antibodies everywhere and, in a cascade of overreaction, other cells desperately consult enormous textbooks to assess the situation. The result is a massive release of histamine by Mast Cell, which destroys entire cell city blocks. This is more or less how many allergic reactions happen. It is also a sample of the way in which the immune system can overcompensate. A similar process—involving a different cascade of exaggerated reactions—is probably responsible for the Acute Respiratory Distress Syndrome that is the cause of death in most cases of COVID-19. (For additional information, see Chapter 22 of the manga, “Cytokines,” where the immune cells become “activated.” The cytokines are embarrassing photographs of their younger cell selves, and spur them to over-action, sort of like too much really strong coffee. Disaster could certainly result from this rather uncontrolled process.)

Neither the manga nor the anime talk about vaccination, but they do provide a loose but instructive metaphor which may aid understanding. We see, for example, that antibodies produced by B Cells serve mostly to alert the neutrophils to neutralize viral or bacterial threats. In the anime, the White Blood Cells’ little receptors pop up and huge battles ensue. In real life, antibody-labeled viruses, bacteria, and infected cells are engulfed. In both, those antibodies don’t last very long, which is why a test for antibodies provides a marker for current or recent infection, but possibly not for long-term immunity.

The real long-term immune power lies with the command and research sections, run by Helper T Cell and Memory Cell. In order to measure permanent immunity from a virus like SARS-CoV-2, we must be able to test for the presence of that one guy in the hat labeled MEMORY in the midst of a platoon of Killer T Cells. This is possible, but not easy. In order to produce an effective immune response by vaccine, we must create a situation in which Helper T Cell and his command department learn to send out the troops immediately in response to the presence of any SARS-CoV-2 virus. The actual process is far more complicated than one Memory Cell remembering an ages-old prophecy of doom and sending a memo to the cells upstairs. But it is as seemingly unlikely and, possibly, just as potentially unreliable.

Nonetheless, Cells at Work! is an enjoyable experience in both manga and anime form. I am sometimes tempted to use the pause button in the anime when medical information overlaps with action, though I mostly find that the sidebars contain stuff I already know. The macho-dude orientation of the white blood cell army is a little annoying, and offset only a bit by a kick-ass woman named NK Cell, representing a super-specialized Natural Killer T Cell. But anything that can make me laugh about the immune system is welcome in these strange times. I am looking forward to the second season.

A darker, harder-working set of blood cells on the cover of Code Black, Volume One

In addition to Cells at Work!, there are several spin-off manga series, done by other writers. Of these, my fellow old ladies who watch anime have been most impressed by Cells at Work: Code Black. In Code Black, a new set of heroic cells strives endlessly to stave off the effects of unfortunate health decisions made by the body in which they reside. They must work around cholesterol buildups, low supplies of oxygen due to smoking, and excessive amounts of glucose, while being plagued with things like gout, ulcers, and erectile dysfunction.

Trailers for the new anime have the same hilariously dark look as the manga. They feature a lot of sweating and exhaustion, since it’s hard to stay properly enthusiastic and perky when there is nothing but endless, thankless work. We are looking forward to laughing about serious medical issues when Cells at Work: Code Black is released. With Cells at Work! season two expected at the same time, January 2021 should be a good month for anime, even if we still can’t safely get a big group together to watch it.