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Hataraku Saibou Ep. 3 - Doctor's notes

Other discussions
Episode 1 - Pneumococcus
Episode 2 - Scrape wound
Episode 3 - Influenza
Episode 4 - Food poisoning
Episode 5 - Cedar pollen allergy
Episode 6 - Erythroblasts and myelocytes
Episode 7 - Cancer
Episode 8 - Blood circulation
Episode 9 - Thymocytes
Episode 10 - Staphylococcus Aureus
Episode 11 - Heat shock
Episodes 12+13 - Hemorrhagic shock

Background

Hello again! I am a medical doctor currently in residency training in the field of pathology. It's my job to study and categorize all sorts of human disease, usually by studying the effect it has on the human body and particularly its cells. Hataraku Saibou is a series written by Akane Shimizu featuring anthropomorphized human cells battling such disease. The creators seem to have a strong penchant for both accuracy and subtle detail, so I am here to help provide an explanation of and background information for each episode so you won't miss anything obscure. Call me Dr. Eightball. Spoilers follow!
More or less caught up now. Sorry, I would have tried to get this out sooner, but I am starting my first week of lab medicine call, and I've been preoccupied with learning, you know, how not to fuck that up. This episode is going to start getting into the details of the adaptive immune system, which you may guess is pretty complex. I honestly had to spend some time with immunology texts between reading the manga and watching this episode. As always, please pay special attention to our consultant Rathurue. I saw some great points made in the general discussion thread earlier, and would be very happy to get more input from even more knowledgeable people.

Character Feature

CD8+ Lymphocyte
Grr, am I ever going to get to talk about neutrophils? Whatever. This episode features a viral infection, so it really merits more discussion about lymphocytes generally, but particularly CD8+ ("cytotoxic) T-lymphocytes. The star of the episode, after all, is jojo new effector T-lymphocyte. Some (extremely brief) background on lymphocytes: These immune cells comprise the adaptive immune system. Your immune system can broadly be split into the innate and adaptive immune system. The innate immune system is always present and always active; neutrophil is a great example of this, along with NK cells and the complement system (later), but we can even extend this definition to include things like your skin and digestive acids, which also play a role in general defense. On the other hand, the adaptive immune response is very specific to a microbial invader, takes some time to ramp up, and results in a robust response and long-term immunity through memory cells. The adaptive immune system can be further split into "T"-lymphocytes and "B"-lymphocytes. As a heuristic, think of T-cells as directly killing, and B-cells as producing helpful antibodies (the reality is more nuanced of course).
Shamelessly taken from: Abbas, Abul K.Lichtman, Andrew H. (2011) Basic immunology :functions and disorders of the immune system Philadelphia, Pa. ; Saunders
So, CD8+ lymphocyte. Big burly scary/intimidating dude. Good choice, considering their role is to directly kill cells, usually through the effect of proteins (perforins & granzymes) which literally punch holes in the target cell's membrane, or through the Fas ligand system which induces apoptosis (tells the target cell to go kill itself). These CD8+ cells are targeted towards cells infected by viruses, which normally express the viral proteins on a specialized receptor on their surface, known as major histocompatibility complex (MHC), or human leukocyte antigen (HLA) class I receptors. The HLA system merits a separate discussion. T-cells are more generally stimulated by recognition of foreign antigens on various antigen-presenting cells (gee whiz), of which the dendritic cell is a great example, but macrophages and B-cells can present antigens too. Recognition of foreign antigens is a tricky matter; lymphocytes (which are normally "born" in the bone marrow and either mature there or in the thymus gland) have a pre-determined and semi-random "range" of foreign antigens that they can recognize, which is defined by an extremely complex mechanism called VDJ rearrangement: https://en.wikipedia.org/wiki/V(D)J_recombinationJ_recombination) . So, there's no guarantee that any one antigen will generate a response in any one lymphocyte. This is going too long, let's get to the episode.

Episode 3 - Influenza

  • Hmm, dark and scary place. Wonder where this is. I'm guessing by the fact that it's where influenza is first sighted it's somewhere up in the nasopharynx. Or maybe Waldeyer's ring!
  • Aw, a naive T-cell, how cute. These are T-lymphocytes that are "mature", but are not yet activated. They can be found in general circulation but are more often concentrated in lymphoid rich tissues (like the spleen, lymph nodes, but also peyer's patches and tonsils).
    • Virus spotted! You may be wondering why virus infections are a zombie outbreak instead of a new character. Consider their size difference; influenza virion particles are maybe 100 microns in size, compared to a red blood cell which would be 75 times that. Not to mention viruses generally have to infect cells in order to reproduce, hijacking the cells normal protein-making machinery to make more virus particles (or alarmingly, integrating with the host cell's DNA).
  • U-1146 to the rescue! Umm, what is he doing fighting virally infected cells? The role of the neutrophil in viral infections is unclear to me, but they are definitely not the main contributor. I'm not even sure how he would recognize the cells as foreign, since neutrophils do not have receptors for MHC class I receptors AFAIK (though they do express MHC I themselves). Oh, we discussed his wall-walking tricks (diapedesis) last discussion.
  • Okay, infocard for influenza time. Influenza is one of the most prevalent and significant viral infections. It's an RNA virus, and not a terribly complex one, with only 8 gene products (hemagglutinin, which helps it bind and fuse with cells, neuraminidase, which helps the virus be released from infected cells, and some membrane/capsular proteins). It normally causes infection in the upper respiratory tract, killing mucus-secreting and ciliated cells (in turn, disabling that part of the primary defense system). Importantly, this promotes secondary infections by bacteria (bacterial pneumonia can often follow influenza).1 Most of the symptoms result from immune-mediated responses, as we will see.
    • Something very important to know about influenza is that it mutates a lot. It undergoes antigenic drift, resulting from minor changes over time, and causing the public health agencies to need to reformulate a new vaccine every year. But it can also infamously undergo antigenic shift, when it reassorts genomes with other flu viruses. This classically occurs in animals (hence "swine flu" and "avian flu"). Oh, and we mostly only have to care about influenza A & B.
Influenza virus particles
  • Macrophage enters the scene! I have referred to them as the immune system's janitors, but they are also incredible multitaskers, killing microbes, ingesting them, presenting antigens, and coordinating local responses. They are also tied for my favorite immune cell (along with B-lymphocytes). Will defer further discussion to a future episode.
    • Clever interaction! Helper CD4+ cells are called upon to coordinate an immune response. I'm not sure if it's fair for macrophage to just be able to phone it in though. I would have expected that she would carry the debris to a lymphoid center, or maybe passive flow of peptides would get picked up by the dendritic cell.
    • CD8+ cytotoxic lymphocytes are in-bound. Something to mention, is that during infection, there is passively increased flow of CD8+ lymphocytes to the site, but whether or not they stick around depends on if there is any antigen they can recognize. Perhaps these guys have seen influenza (or similar) before? Also them being dicks to newbie is not any specific behavior I'm aware of, lol. Neither is backup neutrophil needing a tug.
      • Oh yeah, I guess there's a memory T-cell among them. Any adaptive immune response should normally generate some memory B/T cells that will generate a much, much faster reaction to a repeat infection than the first time around. Against infections that don't have much genetic/antigenic variability, this works great (you only get chickenpox once, right?), but against something like influenza which mutates constantly it is less helpful.
  • I think the naive T-cell is retreating to a lymphoid center. This gets a little convoluted for the sake of making a better story. Remember that the activation of the CD8+ cell is done by antigen presenting cells, which this dendritic cell certainly is, but generally the APC would have encountered the antigen first. It's by display of the peptide that the lymphocyte is activated, though a motivational speech is nice too.
    • "One feature unique to CD8+ T-cell activation is that its initiation often requires cytoplasmic antigen from one cell to be cross-presented by dendritic cells. Another characteristic...is that their differentiation...may require the concomitant activation of CD4+ helper T cells."2 All right, let's not get too far into the weeds.
  • Oh btw, I don't think the infected cells really try to fight back against the immune cells much, lol. Mostly they sit there churning out viral particles.
  • Activated T-lymphocyte! Now we have a subset of lymphocytes that is specifically targeted towards this particular flavor of influenza (via clonal expansion of this specific cell). In reality it would have taken him a few days to show up.
    • B-cell shows up too. Okay, I must ask for your patience as I defer talking about him until later. We can't talk about ALL of adaptive immunity in one reddit post. Just know that he produces antibodies, though usually from a distance, and his antibody production is very specific and similarly programmed as the T-lymphocyte response is.
  • Time for systemic response! Activation of immune cells (as well as responses from nearby stromal/epithelial cells) normally generates numerous cytokines (in this case probably things like interferon-gamma, interleukins 1 & 6, and so on); these generate a response in the hypothalamus that increases the "set point" of body temperature (fever), and a lot of the other general symptoms of malaise that we tend to refer to as a "viral syndrome". I am actually intrigued by the loss of appetite, I will read up on that for later.
  • Oh shit, this virus is able to handle our CTL. This represents a virus that has undergone further genetic mutation and thus is not (yet) recognized by the immune system. Give it a few more days though.
    • Type A influenza is the form that is known to infect animals and thus is prone to antigenic shifts. Actually, I think we are forced to assume this is a new virus from outside the body.
  • Platelets and dendritic cells don't have any real interactions that I'm aware of. Waiting for that primary research article to prove me wrong though, lol.

Summary

A pretty substantial infection, influenza is no joke. While most people get through it just fine (though they will feel like absolute shit for the majority of it, with fever, upper respiratory symptoms, headache, and muscle aches), it can be very dangerous in vulnerable populations. You may have noticed that there has been no help from "outside" the body so far. The first two cases probably wouldn't have come to clinical attention, but I bet this would have. Alas, treatments for influenza are few (neuraminidase inhibitors, amantadine), with questionable efficacy and a very narrow timespan of effectiveness (eg first 48hrs of symptoms). Usual management would just be supportive (fluids, rest).
Next episode looks like it could be complex as well. Food poisoning is a broad category and can involve many different toxins and pathogens. Good thing I have the manga to read up on now...
1Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. 2013. Medical microbiology. Philadelphia: ElsevieSaunders.
2Abbas, Abul K.Lichtman, Andrew H. (2011) Basic immunology :functions and disorders of the immune system Philadelphia, Pa. ; Saunders
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Frequently asked Freshmen Questions: A Thread

Updated as of 6/15/19.
Added: Housing, Degree Plans, and other Resources into the thread! Make sure to read updated thread!

It's that time of the year, newly admitted students are starting to enter the university system and come to this subreddit to gain some info about the university. To avoid flooding this subreddit, I think making this mega thread is a lot easier than answering individual questions.

"I got in now what?"
- First off, congratulations! You've probably worked hard throughout high school (and maybe college) to be admitted into this university! Some insight, this university is large, and its easy to know a lot of the programs and opportunities of how it works. Further, Austin itself is a rapidly growing metropolitan area that is in itself it's own beast. Here's some of the things that many, including myself, have grown to learn about the university. Note: This I'll try to updated this thread frequently in order to help out anyone new to this area.

Classes:
- Every class that is going to be offered at UT is going to be found in the course schedule page. Most classes will have their room number, professor, meeting times, and registration status within this page. Make sure that you have no bars and that you meet all the pre-requisites for registering into the class.
" What if my class is open; reserved , waitlisted, or closed? "
Closed: Chances are, you won't get in it. Your only option is to wait until people have the opportunity to drop the class or the day that tuition is due (some people forget to make the payment and consequently get unregistered).
Open; Reserved: It's more than likely means that the non-major spots have been filled up or you need to have a special qualification to enroll into this class (Honors, ULN, FRI, majoring in "X", upper-division standing, etc.) Unless you meet these qualifications, you can't enroll in the class
Waitlisted: You have to wait, and that's about it. There's no way to skip to the front of the line, just see how many people are in front of you in your "See My Waitlist" page. Rather than that, hopefully you'll get in but please do have a back-up plan in case the waitlist never reaches you.

Registration:
- Registering is stressful, especially at orientation. The best thing to do before registering is to make sure you have classes ready in a separate note document with their unique numbers. Also, don't count on your registration to be perfect, at least not your first one. Make sure to talk to your advisor, clear all your bars at registration, and have some schedules ready. Rather than that, here's some tools that can help you when registering.
"UT REGISTRATION PLUS"
- This is the tool you want. It has grade distribution, professor ratings, and a schedule planner all-in-one and works with the course schedule. Also, this Chrome extension was made by a UT student, make sure to check it out.
"UT PLANNER"
- Pretty much self explanatory. You choose your courses, see which unique numbers work with each other, and plan out everything. I'll give this one kudos for having an option of alternative schedules, as opposed to one.
"UT CATALYST"
- Shows grade distractions for an overall course and for specific professors. Has cumulative and term-specific options.
"RATEMYPROFESSOR"
- Let's you know how other students at UT feel about a specific professor. Make sure to pay attention to what term and course the rating is coming from as the rating for professors may vary. Although the ratings vary from person to person, don't solely pick a professor based on their rating.
"REGISTRATION INFORMATION SHEET"
- This is how you know at what time you're gonna register and if you have any bars.
"REGISTRATION PAGE"
-Simple enough, this is where you'll register.

Frequently Asked Questions:

"What classes should I take for my first year?"
Hey, I get it, you want to make sure your on track. Check out your degree plan for what is recommended every single semester of your four years on the 40-acres. I'm providing links to the CNS Degree Plans, COLA Degree Plans, some of Cockrell's Degree Plans and McCombs Degree Plans. Also, make sure to talk to your advisor.
"How do I claim AP/IB credit?"
First, make sure your score is eligible through this link. After that, if you are certain you want to claim credit from any exam you previously took in high school, go tothis page and claim credit. Credit is $10 per hour claimed so claiming CH301 would be $30.
Note: Only scores you previously sent to UT will be in your account, if you haven't sent them. You have to first go to your College Board account and request to have them sent to UT there.
"I want to/took classes somewhere else, will they transfer?
If you want to make sure that the classes you've taken or are planning to take, look at this website. It will tell you what colleges are eligible, what classes are eligible, and what the equivalent class at UT is.
"How can I tell how much of my degree I've completed?"
Use the Interactive Degree Audit to see how much of your degree is completed with the classes you're currently registered for. There's also an option for planned classes if you want to plan ahead.

Housing:
Considering that most Freshmen opt to live on-campus, we're gonna be focusing on dorms that are on UT grounds (no Castillian, Dobie, Callaway or other dorm-style housing).
"What the best dorm?"
There is no "best dorm" but certain places do have their perks. The large dorms (San Jacinto, Jesters, Kinsolving, and Duren) all are close to each other and offer similar perks. Here's a little rundown on the larger ones.

Duren: As far as I know, this is the newest dorm on campus. It's nice, it's new, has private/shared bathroom options, and it's North. If you don't mind eating at Kinsolving a lot, Duren is for you. Only downside is that a lot of people see "new" and will instantly jump the gun on it. If you don't have the first or second picking day, look at other options as this dorm fills up quickly.
San Jacinto: The "athlete dorm" is also very nice. It has its own Cafe-style restaurant, private/shared bathroom options, close to J2 and JCL, and is close to the stadium. If you couldn't make it Duren on time, try here.
Jester: The largest dorm complex, so large it had its own ZIP code at one point. Jester is split up into Jester East and Jester West.
West houses almost everything. JCL, J2,JCM Jester Auditorium, Wendy's, Boba, and the Sanger Learning Center to name a few. Jester West is the largest, dorm on-campus. I've heard some problems on the elevator wait times and the hot water amongst the higher floors in the building. Also, West is currently finishing the process of renovating all of its floors so be on the lookout for lower floors.
East is smaller, more quiet, and fully renovated. The distance between you and all the things that West houses is almost negligible. There are some private/shared bathroom options within East (and maybe West?) but they do fill up quite fast. Personally, I lived here and never had any problems involving hot water or elevator wait times so East is a good option.
Kinsolving: One of the two all-girl dorms on-campus, Kinsolving is also one of the larger dorms. Comparing it to Littlefield, as far as I know, Kinsolving has larger rooms, shared bathroom options on one wing, and the benefit of having Kins Dining / Kins Coffee on the ground level. Also, no men are allowed unescorted after 11/12 PM (this changes based on what the dorm votes that year) so if you're a girl and don't want to live in a co-ed dorm look for Kinsolving even if you're in honors.

"I want a private bathroom / shared bathroom, not a community one, how do I get one?"
Private/Shared bathroom options fill-up fast. If you don't have one of the earlier picking days, there is a slim chance that you won't wind up being in community bathrooms. However, if YOU ARE in one of the earlier picking days, make sure to check out the available rooms for the dorm that you're looking into, and then compare that to floor plan. This is what Jester East's floor plan looks like. Looking through it, you can see what rooms are near the elevators, at the end of the hall, near the community bathrooms, or have their own private bathrooms.
For every dorm's floor plan, look at this page and choose the dorm that you're planning on living at while choosing when it's time to pick.
"If my roommate has an earlier picking day than me, do I still have to choose?"
No, once your roommate picks what room/dorm you're going to live at, that's also where you're going to live. This is exceptionally useful if you have a late picking day and your roommate has one of the earlier ones.
"I have a later picking day but I want a private / shared bathroom, what are the odds I get one?"
This one's tricky, for the most part private/shared bathrooms fill-up quite fast. BUT there are rooms in certain halls that accommodate for trans folk who do not feel comfortable using the community male/female bathrooms. If these rooms do not get filled up, other students will see these rooms as "available" and will be able to live in a private/shared bathroom space. This is the only case where I've heard of someone in a later picking day being able to get a private bath, though I'm sure you can get really lucky.

Other Resources:
UTMail: Do yourself a favor and make yourself a @utexas.edu account. It's easier to have a student account of the side, gives you updates to what's happening around campus, and makes you look more professional than that @hotmail.com you made 10-years ago.
HBO/Cable: Any student that lives within the dorms is automatically granted access to HBO and other live channels with their contract. Use these resources to watch shows on the subscription-based platform.
SURE Walk / UT Night Rides: Feeling unsafe on campus during the night? Don't want to walk alone at 1am? Don't worry, get a SURE Walk and you'll be accompanied by two volunteers to your locations, if I'm not wrong many times there is a golf-cart-like vehicle to speed the travel times between dorms. Also, if you need a ride home from UT but the bus is no longer in hours of operation or its just too far to walk, request a ride on Lyft with the credit that your @utexas.edu Lyft account is give. Please stay safe.
Note: UT Night Rides does not offer rides throughout all of Austin, make sure your destination is eligible.
Free Microsoft Office Suite: If you attend UT, you are eligible to receive the Microsoft Office Suite for free. Although the set-up is a bit tedious its worth it in the long run. Check out this link on how to receive your free copy.
Discounted Adobe Creative Cloud: As opposed to the normal price that many individuals pay, as a UT Student, you're eligible for a cheaper year-round subscription price to the entire Adobe Suite. Feel free to purchase it online or at the campus computer store at the Flawn Academic Center.
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