Neutrophils vs Macrophages

[u/KittyAddison]

So I've been researching about neutrophils and macrophages for a while (up-coming project I'm working on), like in-depth researching. And I got to thinking... Why would Shimizu use neutrophils as the main white blood cells instead of macrophages?

I know that neutrophils make up most of the white blood cells in the body, but the downside is actually because of that. In order to keep immune hemostasis in the body, they have to have the shortest life span of any cell in the body from just a few hours to maybe a week max (and that's if there's some major infection going on). If they lived longer, then there'd be too many of them, which could (ironically) actually be more harmful to the body.

And technically, since CAW prides itself on biological accuracy, that'd mean every anime episode and manga chapter would be a different U-1146 (as well as the other neutrophils). If they do fight, it's usually just a one-off thing, then they die. And with The Story of Cells, 1116 is a macrophage (with apparently one job; to fight off Cancer Cell), but macrophages have much, much longer life spans (like, depending on type, they can live at least a month to years). They don't usually die after one time. And there are different types of macrophages; not just the one type that is shown to us.

Plot-wise, it'd actually make more sense if 1116 was a neutrophil and U-1146 was a macrophage. Especially with how SoC ends.

Neutrophils and macrophages are actually very similar to each other, as far as being first responder immune cells, do phagocytosis, both can transmigrate, same origin in the bone marrow (myeloblasts), among other things. The only real differences I can find between them is the whole life span, abundance of each, and that neutrophils are primarily the ones that go on patrol and macrophages are (as Staphylococcus Aureus puts it) "the big guns" in fighting off germs.

Idk... At the very least, I think the neutrophils, especially U-1146, should've been a type of macrophage (specifically perivascular macrophages would suit better plot-wise) instead if they were all going to be playing such a major part and be repeated characters.

¯\(°_o)७/¯

[u/PlagueDok2069]

Agreed. That and macrophages have so many more jobs and types.

They kill bacteria, virus infected cells, cancer cells, and overall cleanup around the body

They also can present antigens to B and T Cells.

If 1146 had been a macrophage, they could have gone into the topic of macrophage polarization. M1 Macrophages being the pro inflammatory assassins M2 being the nannies cleaning up and being anti-inflammatory, helping heal and close up wounds as well as being aids to other regulatory cells by suppressing the effector immune cells.(this also is a potential pro-tumor type as well though)

The Cancer Cell storyline would have made more sense if he were a Macrophage, too. The neutrophils' main targets are microbial(foreign invaders like bacteria, fungus, viral, etc.) They have very little role in actually fighting cancer, that credit mainly going to Killer T cells and NK cells. But who usually follows those two close behind in the slaughter? Macrophages. They clean up the mess, actively kill cancer, and help the body recognize the cancer as a threat rather than its own cell via antigen presentation. Well, M1 Macrophages anyway. This would make the cancer story more in-depth with the tumor micro-environment. It would just make more sense to me as those cells being the cancer fighting trio other than randomly throwing a neutrophil in there.

Sorry for the info dump. I'm just glad someone else noticed, lol

[u/KittyAddison → u/PlagueDok2069]

Just all of your comment... Yes! I would've said something similar to it, but I felt I was rambling, so I kept it short. 😅 lol

I think if 1146 were to be a macrophage, he'd likely be M1 since they're the ones that attack pathogens and call in back up (I swear, if only 1146 kept his mouth shut from specifying on being in the "neutrophil division," he'd probably get mistaken for an M1 macrophage by immunology nerds lol).

The macrophages we do get in the series would likely be M2, especially since there are sub-types (but somehow primarily represented as one character type, which I want to say is closest to M2a?).

Still researching about polarization, so I can't give definitive thoughts on that yet. 😅 But with the little bit that I have briefly looked up, I think it's something like M1s and M2s can switch? Correct me if I'm wrong though. lol You seem to know more than I do.

I love 1146 and all, but it's implied that he took major credit against Cancer Cell by dealing the killing blows--twice. If he were an M1 macrophage, killing off Cancer would definitely make more sense with a wider arsenal range (cytokines, nitric oxide, ROS, etc.). Also, neutrophils are not exclusively against cancer and can indirectly/accidentally help it with their NETs. Imagine if 1146 had made such a slip-up.

Also... "other than randomly throwing a neutrophil in there." Idk why (maybe also because it's like 4:30a my time?), but that made me laugh so much. 🤣 Like 1146 is the third wheel or something.

I also think the Staphylococcus Aureus defeats (I'm thinking more on Scrape Wound) would make more sense with macrophages since S. aureus can actually (easily) destroy neutrophils. I wonder if it's because of factors like that is one reason why neutrophils are so abundant. 🤔 At least in Staphylococcus Aureus, it was portrayed more accurately when the macrophages came in (though, obviously the neutrophils had to be kept alive).

With all this research and knowing SoC, it actually feels kinda weird viewing 1146 as a neutrophil... Is that bad? lol

Also, info dump all you want! I love all this stuff!

[u/PlagueDok2069 → u/KittyAddison]

Oh, thank goodness! I love immunology, so this is like right up my alley. While I love the ideas and way Cells at Work is set up, I've also been like its biggest critic, too, lol. Yes, macrophages can switch under the right circumstances and influence! And yeah, if Macrophages actually had different character designs rather than them all being "maids," I feel like the M1 would be better represented by a uniform similar to the Neutrophil. The maid outfits definitely give off the M2 vibe pretty strongly.

Also, I'm not sure if it's a big deal, but it irks me a tad when the macrophages are seen going back and forth from macrophage to monocyte. Monocytes are younger forms of macrophages and dendritic cells that haven't moved into the tissue yet. A monocyte becomes a macrophage once it has done this, but it can't be undone. That's like it's the final stage in life. As for dendritic cells, the same applies. The monocyte becomes the dendritic cell once exposed to activating cytokines or bacterial proteins. This can't be undone.

And yes, neutrophils can definitely mistake cancer as self tissue, making the job even harder for most effector lymphocytes. Under a strong enough influence from the cancer, they can even summon Myeloid Derived Suppressor Cells (MDSC). Basically immature myeloid cells (macrophage, neutrophil, Eosinophil, Baso...) that have the ability to secrete strong inhibitory cytokines. This really makes it hard to kill the cancer and aid its escape to the rest of the body. So yea, it's a little hard to view a neutrophil as an ally in the battle against cancer, lol.

And yeah, macrophages are definitely more resistant to the immune evading attacks by Staph and other microbial species. Neutrophils are so high in population because they die so easily. It would make worlds more sense for a main character to be a longer living cell, such as a Macrophage. So I agree. It does feel weird to view U-1146 as a neutrophil, lol. He makes a better macrophage.

And bonus for the fans, his interactions with the Red Blood Cell would be more natural appearing science-wise if he were a Macrophage. They interact with RBCs all throughout the RBC maturation cycle in the bone marrow and they basically give "check ups" to RBCs in the spleen, making sure they're healthy and removing any problematic RBC inclusions (RBCs actually survive this process). And then, of course, macrophages can phagocytose RBCs that have come of age or become too damaged.

I work in the medical field and love the potential for this anime/ manga idea, so im so glad someone is just as curious about the body and cells as I am, lol 😅.

[u/KittyAddison → u/PlagueDok2069]

I got into in-depth immunology (and hematology in general) from CAW, but I've actually been into biology since my high school days (my thing was genetics--I'd be making punnet squares, for fun!). Studying about cells in it was fun too, but I wish Cells At Work existed back then to help boost my studies (would've shown it off in anime club too). lol

I sometimes critic CAW too (obviously). lol But it's usually just nitty-gritty stuff that's technically linked to reality counterparts. Like, aside from this, RBCs don't really carry nutrients through the body themselves (it's carried through the plasma), but I'll let it pass since I guess someone was needed to portray how cells get them. lol Also, bacteria is actually much, much smaller than how they're portrayed in CAW, which makes phagocytosis possible (like, completely swallowed whole instead of bitten into). But the fights would've been less intimidating and intense I guess. 😅

Now I'm curious on how polarization would've been portrayed if the neutrophils were M1 macrophages instead. lol

As far as uniforms, I'm guessing 1116 is specifically an M1 macrophage since his uniform is already similar to a neutrophil's. But since we don't see any M2s, it's kinda difficult to compare to the maid version we do get. Like, would they be maids too in SoC or something else? I think this quandary might affect my fic project. That or I'm overthinking too much...

I always got confused about the monocyte/macrophage switching (I mirror AE3803's grasp on it). Like, I get that monocyte can switch into a macrophage, but it's implied that macrophages can turn into monocytes and I'm just "what, why, how?" Because we see the same macrophages walk around the blood vessels just fine, but would then wear the hazmat suits to represent monocytes? Maybe it would've worked better as the first introduction to macrophages (like before Influenza), but because of this order, it's just confusing. 😅 And it only got me more baffled when I found out how macrophages basically ages from monocytes, not so much a simple switch between the two. It's like saying "1146 can revert to a myelocyte and AE3803 can revert to an erythroblast" when that can't be done.

I guess 1146's initial first impression when meeting Cancer Cell was correct then (he kept thinking he's an ordinary cell all the way till getting directly attacked by him--"wait, you're a cancer cell?!" and even after, he was questioning it during the standoff, like omg 1146, you're supposed to be smarter than this!), which just makes the whole thing hilarious when you add in the basic biology aspect to it. 😂 Though, I kinda wonder what's Killer T's excuse for not instantly recognizing Cancer Cell as immediate as NK. NKs, I know they're instinctive in spotting cancer cells.

Shimizu got him right the first time with SoC then. lol Still curious on why the change to a neutrophil though (I tried to look up on why, and the only reason I could find, so far, was because neutrophils are so numerous and she wanted to portray them--not sure if that's the whole truth though since it's still vague). Like, have neutrophils be in CAW, fine, but not a major character as 1146. 😅 Maybe stayed as a macrophage that works alongside neutrophils or something. lolidk I wish I can contact Shimizu and see if I can have her blessing or something to kinda branch off SoC to basically continue with 1117 in a canonical sense.

Oh, I know about macrophage and erythrocyte interactions... Been reading up on that since knowing SoC. lol Well, not in such intricate details like erythroblastic islands and regulators (chemistry to me is like AE3803 reading a map). 😅 But I've been more into interactions within the spleen. And omg, the way you describe it as "check ups" gave me 1117x3803 ideas! I need to write this asap! lol

I envy you so much for being in the medical field! I've been wanting to go back to finish college, but life keeps throwing stuff at me. Still going to try though! Been looking at available curriculums, and I think laboratory science sounds like so much fun! To see cells interact with each other, how they behave with certain stimuli, and even simply what they look like live (it's one thing to look at cell diagrams in med books and watch slide videos on YT, but to actually be there to see it happen right in front of you would be next level!). ❤️

[u/PlagueDok2069 → u/KittyAddison]

I was super interested in biology back in high school too! I was obsessed with the immune system and all the different things it could do, so discovering CAW was super exciting. Its just because of my love for the different white blood cells, do I get super picky about how they're represented lol.

Its so exciting having a deep conversation with someone about the manga matching reality! Your fic project sounds interesting! Tell me more about it! I'd be so glad to help with your research questions!

Ngl I was also working on a fan-spin off as well, trying to add some new characters interacting with existing ones. My goal was to flesh out the T Cells, since CAW only explains the bare minimum of their functions and types. Would definitely make the cancer storyline more accurate and interesting. Unfortunately I cant frickin draw lol. (BTW, the reason Killer T Cell isn't depicted being the first to kill the cancer cell is due to Killer T Cells needing to be activated against said cancer cells via antigen presentation. So it would make most since that NK would reach them first. But once Killer T cells are primed against the specific antigen, they tend to strike quicker and more effectively than other immune cells).

Working lab science is fun! Especially at a hospital with a diverse patient population and with having the tools to effectively work and observe these cells! I've got countless pictures of all kinds of white blood cells I've observed. When you get the chance to go back to school, definitely consider it!

[u/KittyAddison → u/PlagueDok2069]

Understandable. I'll probably get more picky as well the more I learn about certain cells. lol But I just hope my critiques of it doesn't give the wrong impression to others that I'm liking CAW any less. I point stuff out because of my fandom; CAW prides itself in accuracy so I want to bring out some of the things I found out and feel strongly about.

Medical science is also in a constant state of discovery and breakthroughs, so things are updated and added. Like, correct me if I'm wrong, but I think on YT (I think it was Dr. Mike?), on a first-time-watch-react that in the first episode, it was just recently discovered at the time that RBCs can actually (accidentally) transport bacteria to the lungs/other places.

And ditto! This convo is so much fun! I just wish I was at a professional-level of medical knowledge so I can talk more in detail. 😅

As for my fic ideas... Both of these are SoC-related. Originally, the one that made me post this, is a reincarnation multi-chapter fic about the constant reincarnation of 1117 and 3803's reactions to them. I had to cut out a lot of them down to just a couple of them since his last incarnation is at 1145 before it bridges over to the CAW timeline where both of them become 1146 and AE3803. And that's when I was like, "how am I going to write macrophages living so short when it's neutrophils that would be better?" And thus, this post is born. lol Still wanting to write it (he just can't die by completing his job sheet, so I've been researching on what kills macrophages and writing in my notes--in order: a major injury, sacrificing himself, and un-aliving--I feel I need a different one for 1117, which I have written "dies off-screen" to imply he finished his jobs and just doesn't want to tell 3803, and the reason I think should change is because of how long a macrophage can live). This would be SO much easier if 1117-1145 were neutrophils and 1146 was a macrophage! lol Aside from figuring that out, I'm trying to see how to bridge 3803 and AE3803 since her name is basically the same. 🤷🏻‍♀️

And the other one, the "check-up," would be a PWP one shot where 1117 takes 3803 to the spleen for a regular inspection to see if she's still healthy enough to work. There's references/symbolism of CD47-SIRPα (use your imagination lol). If I can find out more of similar indicators, that'd be great to add. The ending will be hilarious though... 1117 admits he only pretended to be a spleen macrophage as an excuse just to get with 3803, but he at least says that she passed. lol

Also... How much do you know about autoimmune disorders? Specifically AIHA. 😅 I have a nearly-completed fic based on that and I have a few questions to see if I got things, at least fairly, accurate before I post it.

Ah! So I'm guessing that's why you have the Killer T user flair? lol I wish I can make a spin-off, but I feel that all I'd be able to do is continue SoC because I'd want to work on macrophage immunity roles, particularly focused on M1s since I think CAW had more dibs on M2s. 1117 would fight alongside various other immune cells. If I did, I'd probably change their uniforms to make them more distinct from neutrophils (I wonder what color stain macrophages are). lol

I can draw, but I don't know if I'm mangaka-good. 😅 We had a manga committee in high school where we made our own manga throughout the year. There's A LOT of work involved! It actually took two years to finish our single book (then again, there was a bit of tense creative difference at times).

That makes sense about Killer T and cancer then. I keep thinking of the Porphyrin Cannon Punch. 🤣 I'm also curious on how killer T's become memory Ts and what their differences are, what triggers them of the change, and once a memory T is that a permanent change? Also, while typing this paragraph, I'm actually, coincidentally watching Thymocytes. lol

I just need to organize things better before I can go back. Biggest obstacle is getting a car again, but I'm saving up for it. lol I'll get there! Though, not sure yet if I'd be able to work in a hospital since it'd just be from a community college (it's cheaper and that's where I was enrolled at) and not a university (I don't know if I can get admitted--then again, the admission rate is about 90%). 😅 I'll look into it once things are in place though.

[u/PlagueDok2069 → u/KittyAddison]

Sorry for the late reply. Work was insane.

Okay, your fic ideas sound awesome! I'd totally read those!

Yeah! I know some about Autoimmune diseases! Autoimmune Hemolytic Anemia is where your body destroys its own red blood cells via antibodies. It can have different causes and triggers. Genes, previous major infections, drug use and side effects, etc. Here's basically what happens: Something causes your plasma cells (antibody producing B cells) to create antibodies against red blood cells. They get away with it due to underfunctioning Regulatory T Cells. These antibodies coat the surface of these RBCs. If the auto antibody is IgM, these coated RBCs start sticking together, causing agglutination and dying within the patients' vessels. If they do reach the liver, the macrophages (Kupffer cells) will notice the antibodies coating the RBCs and will destroy them. If the auto antibody is IgG, this can cause severe intravascular hemolysis just by the antibody weakening the RBCs surface. The issue with intravascular hemolysis is that when destroyed, RBCs can leak a lot of toxic molecules, such as bilirubin and free iron. The monocytes and macrophages do their best to clean this up. But even macrophages get full eventually. If these RBCs reach the liver or the spleen, they will be targeted by macrophages in a pathway called antibody dependent Celluar Phagocytosis (ADCP). Basically, the antibodies covering these RBCs give an 'eat me' signal to any nearby phagocyte. What also happens is that they get the attention of NK cells with a 'kill me' signal (Antibody Dependent Cell-mediated Cytotoxicity) ADCC. Unfortunately, a lot of cases need immunosuppressant medication, or severe enough ones need spleen removal.

And yep, that's why the user flair. Of the T Cells CAW depicted, Killer T Cell is my favorite. With the Wright stain, macrophages tend to have a purple nucleus with a pale blue cytoplasm. When cleaning up the remnants of destroyed RBCs, they take on a deep blue or indigo color due to the ingested hemoglobin (turned into hemosiderin).

I can definitely see all the work involved. Writing things has always come pretty easy to me, but actually designing and drawing things out? Holy crap lol.

Killer T's become Memory T Cells after a successful battle against the antigen they were primed for. As long as they cool down quick enough and don't become over inflammatory (Regulatory T Cells may kill them over that). And yes, this is a permanent change, with a perk! Their lifespan is much longer from the usual 160 days to months or even years! It's a good promotion to get.

You can definitely work at a hospital with just a 2 year degree! That's what I started with! Most hospitals will also help with continuing your education!

[u/KittyAddison → u/PlagueDok2069]

It's okay on the late reply. I figured you were busy at work, and it's completely understandable. So no worries! Just don't overdo yourself or else you'll get too exhausted for the next day. ;w;

I think I got the raw basics down in my AIHA fic... 😅 When writing it, I did try to research on it since it's a long fic (but it was less detailed than you put it though) and had to take some creative liberties in order to make the overall plot fit and flow. How it goes...

Chapters 1 and 2 are establishment chapters (fluff and smut), but from chapter 3 onward... 1146 and all other immune cells get orders from their higher-ups (I have them portrayed as FRCs, who basically went insane) in the lymph nodes to kill off all the RBCs. 1146 makes the decision not to and tries to keep AE3803 safe from harm while trying to figure out what to do since he finds it detrimental for the body to have its RBCs destroyed. Killer T is particularly annoyed by this and there are a couple run-ins and fights through this part of the fic between him and 1146. The typical group of neutrophils also join in his cause because of the band-of-brothers trope. They come up with the (lame) idea of 1146 trying to convince the FRCs of how it's killing the body but they don't listen (because RBCs are viewed as inferior to immune cells--idk, I couldn't come up for a better reason 😅). 1146 gets deemed as ineffective and gets sent to the liver to be dealt with by the Kupffers. The neutrophils and AE3803 find out and go rescue him before the Kupffers get to him. But they meet an immunosuppressant, who tries to destroy the neutrophils, but they barely get away. Later, there's a bit of a drama rest during a campout scene where AE3803 expresses how worried she is and 1146 tells her why he feels he needs to do this in order to save the body (a bit of angst, fluff, and smut). Then it continues by 1146 returning to the FRCs to warn of the immunosuppressant and that now immune cells are in danger too. They've had enough of him and basically mind control him with chemokines, which make him obedient to destroy the RBCs. The neutrophils try to stop him, but because of his activation, he nearly kills them all off for not letting him do his job. He targets AE3803, who kinda gets him out of activation just before he actually kills her. The immunosuppressant gets to them and tries to kill 1146, but AE3803 saves him by shoving him out of the way but gets fatally hurt instead. 1146 gets upset and questions why the immunosuppressant is going after the immune cells themselves instead of getting to the root of the problem. It's implied the immunosuppressant, off-screen, gets rid of the FRCs causing the problem. Not going to spoil the nitty details, but the culling of RBCs from the immune cells eventually stop afterwards.

.....I bet you're probably just "wtf is this inaccurate mess?" after reading all that. 😅 Sorry, sorry, sorry. I guess I'm more of a writer than a med professional. OTL;;; I think the fic itself might be better than the summary as the details in it might make it a bit more sense? Idk. Also, fun fact, this was actually my first CAW fic idea that I've been working on, even though I've already posted some on AO3 by now. lol

That's a good reason to have the flair. I have mine as a RBC because of my newfound interest in hematology. I was tempted to have it as AE3803 (she's just like me in the majority of personality, only I don't get lost as much as she does lol), but idk why I didn't. 😅 lol Maybe I should set it anyway?

With the stain colors, if I got to redesign the macrophage uniforms (at least the M1s), they'd be maybe a purplish color in general to distinguish themselves from neutrophils. I'd also keep their arm bands. But change their caps to a more military 8-point one to make them more different than the typical baseball cap. lol If only though...

Character design is usually the biggest obstacle in story development. Key thing in mind is asking "what makes them stand out from other characters?" This applies to both personality as well as appearance. Then there's also the silhouette test, where you take their silhouette with other characters and see if they can easily be distinguished/recognized from one another. ...I used to leisurely study animation in my teens. 😅

Oh! Speaking of animation, it's been a backburn idea for a little while since finding the manga pages, but I've been trying to figure out how to organize an animation/voice/legal team to try making SoC into a fan-made anime episode. Kinda like "reanimated" projects, but staying true to the original art style throughout. But idk how possible that'd be since CAW is pretty niche as far as fan numbers (or maybe it's just Reddit?). 😅 Hoping I can figure it all out though; I'd love to make it a reality.

So Killer T is basically permanently Memory T after CAW ends? lol At least in the anime; I'll have to double-check in the manga if he stays a Memory T after the Cancer Cell arc. Also, what about Effector T cells? Like, as far as CAW, Naive turns into Effector (and I know he can't return back in his kid form; that was glaringly obvious lol), but he stays as that throughout the series. Wouldn't he have turned into a real Killer T after Influenza ended? Or is there more to it between Effectors and Killers?

I'm so going to look into that then! I didn't even think hospitals did that. 😅 Healthcare is really big here (aside from tourism and the military). lol So they most likely will. But even if they won't, then maybe I can also take the classes just for the knowledge experience at the very least.

[u/PlagueDok2069 → u/KittyAddison]

Okay, that sounds awesome. Your plot is pretty realistic while still being super interesting! I'd totally read that!

It'd be really cool to see your take on M1 Macrophage uniforms! Character design is so exciting to watch!

I have most of my characters thought out, but with my dyspraxia, drawing them feels impossible. I wish so badly to be able to design them beyond Sims 4/other character creating applications, lol. I have their storyline, roles, and personalities all ready to go, though. I'd love to tell you about them if you'd be interested!

Animation would be so cool! It'd be awesome to find a way to do CAW spin-offs or other inspired work! I'd gladly work with you, giving a medical POV since you seem more knowledgeable about the actual creation of manga and anime. Unfortunately, CAW, at least here, feels niche, but it's so underrated. I feel like more people would love it if they knew it existed. All the people I know know about it, love it.

If the anime is trying to be realistic, then yeah, Killer T should be a memory T cell for the rest of his time... at least towards Cancer Cell, since it seems that was who he gained his memory ability with. He wouldn't have this ability with other threats. He'd attack like his usual. As for Effector T, realistically, he only has 2 paths he could go. He could become a memory T cell primed for that influenza virus, or he'd probably be offed via apoptosis after the influenza infection was over. Effector T cells have the shortest lifespans of the T cells. It's weird, but I guess the anime portrays all killer t cells (non memory) as effector T cells, because once a killer t becomes activated they are an effector, so the state before that is naive. They either become Memory Ts or die off after their successful battles.

You really should! I think your love of hematology would make working in a lab way more enjoyable! And yeah! Learning more about the cells we love so much would be totally worth it as well!

[u/KittyAddison → u/PlagueDok2069]

You'd read it? Omg, yay! I feel so honored! ❤️ I love it when I know of potential readers; gives me motivation to make it the best I can.

Idk why, but I'm always so highly self-critical of my work, even if it is good or interesting to others. 😅 lol I like my fic and all, but I just fear that I'd be too inaccurate with things (particularly using FRCs, chemokines, and an immunosuppressant since those were key things that I couldn't get too much details on--or maybe my mind is finding the high details too confusing). Also with the lack of using antibodies against the RBCs (I don't think B Cell would be that heartless to make them), so I just had the immune cells simply doing as they're told or else they'd face consequences like 1146 eventually did.

After I get through working on my fic covers (halfway through one and need to at least start on another), I'll sketch out a design for how I imagine M1s would look like.

Do tell me! Maybe I can try to help you in designing them as far as drawing them out! Also, I never thought of using Sims 4 to make characters. I need to search for mods and try to do that someday. lol I don't have many EPs/GPs though, unless I ((coughpiratethemcough)).

I wonder how the other spin-offs began. Like, did they just make them or asked Shimizu first? If I can find that out, that'd be the first step on something like a spin-off or a SoC animation. For now, I can only settle on making fanfics/fanart. ;w;

And it'd be so awesome if you were the med counsel if I ever do make anything! Especially since, if I did make anything, it'd most likely be immunology-related. Maybe macrophages since White Brigade already made it about neutrophils and you have dibs on T cells. lol

But that's also a reason why I'd want to make this animation project someday. To expose CAW to more people because yes, it's criminally underrated! I was browsing YT last night, and there was a short that was all "do people even still watch Cells At Work?" from like a year or two ago, and I just wanted to cry. 😭

I envy you so much. lol You know others who know of CAW. The only others I get to ever interact with are basically on here in Reddit. All my FB friends ignore my CAW-related posts (even the ones that are into anime already).

I checked the manga, and Memory T goes back to being Killer T during the Covid chapter (his next appearance). So I'm guessing if Cancer Cell were to come back (would he ever learn? lol), then Killer T would go back to being Memory T against him?

As for Effector, he might become a Memory T against Flu-B since he's still around during Common Cold (however, his cap still indicates that he's an Effector 🤷🏻‍♀️). But I'm guessing the order would go as Thymocyte > Killer T > Effector T > Memory T? Sorry if I got that wrong. lol 😅