Immune System, Part 3: Crash Course A&P #47

By Adem Lewis / in , , , , , , , , , , , , , , , /

It is time! We have arrived at the final conflict. The battle royale. A fight to the…well, hopefully not death,
but a big fight anyway. It only seems fitting that we spend this,
our last episode of anatomy and physiology, talking about one of your body’s last-ditch
efforts to defend itself, at all costs. This is what happens when all the other failsafes
have failed. Your skin and mucous membranes did what they
could, as physical barriers against infection. And your humoral immune response cranked out antibodies,
in an effort to keep your interstitial spaces healthy. But when those systems weren’t enough, your
cells themselves were breached. And pathogens and abnormalities began to run amok where
antibodies could not get to them. Now, it becomes the business of your cell-mediated,
or cellular immune response. And that’s where stuff gets real. Where
cell fights cell. And where the heroes look like T lymphocytes. These lymphocytes, known on the streets as
T cells, go after body cells that have been hijacked by things like viruses, or bacteria,
or become cancerous. T cells cause inflammation, activate macrophages,
get other T cells fired up, and generally regulate much of the immune response. Which is important, because — of all the
ways in this course that we have described how you could die — two that we’ve neglected
to mention are what happens if your body completely fails to protect itself, and what happens
if your immune system goes rogue, and attacks your own, healthy cells. But even when they’re functioning well,
some of your immune cells are careening around your body like miniature, biological versions
of Mad Max war boys. Amped up on signaling chemicals, scouring
the terrain for hostiles, and covered from top to bottom in the dismembered parts of
the enemies that they have vanquished. They’re out to protect all of the tissues
and organs and systems that we’ve been talking about for the past 46 weeks. And these guys play for keeps. If there are cells in your body that look
and act like they’re from some post-apocalyptic hellscape, it’s gotta be the cells in your
immune system. Aside from the fact that they go around literally
eating their enemies, and have names like “natural killers,” some of these cells
are dressed for the part, too. Specifically, they go around wearing parts
of the organisms that they’ve killed, so others can see them. Sounds a little bit messed up, but we’re
talking life and death here. The stakes are high. And this kind of behavior occurs both in your
innate immune response and your acquired response. We’ve already talked about how, in the innate
response, when a phagocyte sees a suspicious character, it engulfs it, and kills it, right? But what we didn’t get into before is that,
during its attack, the phagocyte actually breaks the pathogen into tons of tiny molecules,
and then proudly displays those broken bits in grooved proteins on its outer membrane. These proteins are called major histocompatibility
complexes, or MHCs. And they’re a lot like how Vlad the Impaler decorated his front yard
with the bodies of his skewered enemies … or how a battle-crazed warrior might show off
a necklace made of knucklebones. Because cells from both your innate and adaptive
branches do this grisly accessorizing like it’s their job, they are referred to as
professional antigen presenting cells. Which might make you think, “Is there an
amateur version of an antigen presenting cell?” and yeah, there kind of is. Every nucleated cell in your body — which
means all of your cells except for your red blood cells — have one kind of MHC protein
on their surface, called class 1 MHC. MHC 1 proteins present short chains of amino
acids that are based on endogenous proteins — that is, proteins synthesized inside that
cell. So if a particular cell is healthy, the antigens
on its MHC 1 tell roving immune cells that everything’s ok inside, nothing to see here. But if the cell is, say, cancerous and it’s
making abnormal proteins, then it’ll fix bits of those proteins to its MHC, which alerts
immune cells that there’s a problem inside, and basically asks to be killed. Now: your immune-related cells — like macrophages,
dendritic cells, and B cells — wear class 2 MHC proteins on their outsides. These are the professionals. Class 2 MHC proteins bind to fragments of
exogenous antigens, like a virus that’s been engulfed, broken up, and displayed to
get the attention of other cells. And this is how MHCs are totally essential
to the cellular immune response. Because, the heroes of your cellular defenses,
the T cells, can’t actually detect whole antigens — they can only recognize them when they’re all
diced up and decorating an antigen-presenting cell. T cells are made in the bone marrow, but they
mature in the thymus, the lymphoid gland that sits on top your heart, and which is actually
what the “T” in “T cell” stands for. And you have several different kinds of T
cells, but the two you really have to know about are the helper Ts and the cytotoxic
cells. Helper Ts themselves can’t kill, but they
can activate cells that do, and they help call the shots for the whole adaptive immune
response. Meanwhile, cytotoxic cells are the ones that
actually do the killing of the cells gone bad. Now, much like how a naive B-cell carries
antibodies for one specific antigen, a naive helper T cell has receptors that will only
bind to one specific combination of a class 2 MHC and a particular antigen. If that match is right, the Helper T bonds
to the MHC-antigen bit and it gets activated. Then, just like with the B cells we talked
about last time, the Helper T starts copying itself like crazy, making a few memory T cells
as well, which remember that particular antigen should it meet one again in the future. And it also produces a whole mess of effector
T cells — mostly more Helper Ts, but also some regulatory T cells that I will get to
in a minute. But the main thing the helper T cells do is
raise the alarm that tells other immune cells that there is a problem. And they do this by releasing a cocktail of
chemical messengers called cytokines. When a cytokine enters another Helper T, that
cell usually starts dividing, making more memory T cells and more Helper Ts, which release
more cytokines that keep boosting the signal. And some of those cytokines also go on to
help activate the cytotoxic T cells. You know that macrophages from the innate
system just sort of roll up and swallow pathogens whole…. but cytotoxic T cells do their killing
a little differently. They roam the blood and lymph, looking for hijacked
amateur body cells that are asking to be killed. Basically, these infected cells are already
dying, so they’ve digested some of their invader’s proteins, and stuck them on some
of their class one MHCs, effectively waving a surrender flag made of fragments of the
very virus or cancer that is destroying them. If a cytotoxic T cell with the right receptor
floats by, it binds to the antigen-MHC combination, and moves in for a mercy killing. It does this by releasing special enzymes
that punch holes in the cell’s membrane or otherwise trigger apoptosis, killing both
the cell and whatever is inside of it. Then the cytotoxic cell just detaches and
continues to run down other prey. So by now it should be pretty obvious that
without T cells, there basically is no adaptive immune response. And it really all comes back
to the Helper Ts. Which is why immunodeficiencies can be so
deadly. AIDS, for example, is caused by the human
immunodeficiency virus that specifically attacks Helper T cells. And without the Helper T’s,
there wouldn’t be much of a humoral response, either. Because the cytokines that come screaming
out of the helpers not only activate other T cells, but they also finish the training
of the B cells. The fact is, most of your so-called naive
B cells don’t get fully activated — and become memory or effector cells — when they
first bind to an antigen. And there’s a good reason for that. Since antibody receptors are generated randomly,
you might wind up with B cells that could bind to your own, healthy proteins, like,
say, your growth hormone. So, once a B cell interacts with a substance
— whether it’s growth hormone or some dangerous bacterium — it still needs to bind to it, engulf it,
and present some fragments of it on its surface. But then, it’ll stop, to await inspection. It pauses until the right Helper T cell comes
by to check out its presentation. If the T cell binds to the presented fragment, then
it releases cytokines, which fully activate the B-cell and suddenly you’ve got antibodies
going everywhere. But if it doesn’t, then the B-cell just goes about
its business and doesn’t trigger an immune response. This check and balance between Bs and Ts is
an important safeguard against your immune system becoming too good at its job. Which is a very real risk. A hyperactive immune system can cause mayhem
by losing its ability to distinguish enemy from self, as it turns on your own body. Your regulatory T cells — another type of
effector — help prevent this by releasing inhibiting cytokines that tell other immune cells to
stand down once the initial threat has been handled. Without that regulation, the body might start
cranking out too many antibodies and cytotoxic cells that could damage or destroy its own
tissues. This dangerous confusion is what causes many
autoimmune diseases — like multiple sclerosis, which eats away at the myelin sheaths
around neurons, or Type One Diabetes which tears up the pancreatic cells that make insulin. So the takeaway here is that your immune system
is usually really good at its job, which is to kill stuff in the name of keeping you alive. And you really don’t want it to go rogue
on you, because if there’s one thing you should have learned in the past year with
us, it’s that your body is both resilient and fragile, and it survives only when the
sum of its many complicated parts stays balanced and works together. And that is the glorious wonder of you. As we wrapped up our tour of the immune system
today you learned how the cellular immune response uses helper, cytotoxic, and regulatory
T cells to attack body cells compromised by pathogens. We looked how cytokines activate
B and T cells, and what happens if your immune system goes rogue and starts causing autoimmune
trouble. Thank you to our Headmaster of Learning, Linnea
Boyev, and thank you to all of our Patreon patrons whose monthly contributions help make
Crash Course possible, not only for themselves, but for everybody, everywhere. If you like
Crash Course and want to help us keep making videos like this one, and teaching courses like Anatomy
& Physiology, visit This episode was filmed in the Doctor Cheryl
C. Kinney Crash Course Studio, it was written by Kathleen Yale, the script was edited by
Blake de Pastino, and our consultant is Dr. Brandon Jackson. It was directed by Nicholas
Jenkins, edited by Nicole Sweeney, our sound designer is Michael Aranda, and the Graphics
team is Thought Cafe.

100 thoughts on “Immune System, Part 3: Crash Course A&P #47

  1. You guys are so awesome. I'm in graduate biomedical engineering and I can't emphasize enough how invaluable your clear and concise videos have been to me (not to mention how fun they are to watch!). You rock, keep it up! DFTBA

  2. I'm not going to lie, I came to part 1 looking for some basic information about immune systems. I got it pretty early on, but then I got hooked! So now I'm on part 3 and I'm not sure if I'm procrastinating or not.

  3. Dendritisk cell tar bitar ut av mikrober, far till närmaste lymfen, den letar en T-hjälpecell med rätt antikropp, den aktiveras (virgin) och börjar duplicerar, några blir i lymfen som T-minnesceller. Andra går och strider mot mikrob, andra går i mitten av lymfnoden och aktiverar B-lymfceller som duplicerar sig och börjar bilda antikroppar.

    Fagocyter konsumerar och kommunicerar ytprotein till lymfocyter.

    T-lymfocyter dödar infekterade celler

    Fagocyter kan döda kroppets egna celler om de är infekterade av virus, bakterie, cancerceller
    Infekterade celler slutar producera ett ytprotein som friska celler producerar och fagocyt gör mha enzym så att de tillför programerad celldöd

    Värme och inflammation accelerarer cellmetabolism så de kan repareras snabbare

    Lymfocytor från benmärg

    För mycket för att handla-> signalerar hypotalamus för att höja temperatur

    Antikroppr kan
    neutralisera (omge virus så de kan inte gå in)
    Klumpa virus
    Singalerar andra fagocyter och lymfocyter

    Babyn får i mamman antikroppar och från mammas mjölk

    Skin och mucus membran

    Cytokiner sprider signal

    Hjälpr T cell aktiverar B celler. Hjälpar t safegusrd checkar

  4. Hank, you have a real passion and talent for teaching, and like so many other people have said, it’s extremely helpful! I am so interested in learning, and although I use these videos for class, I will continue watching them for fun because they’re just that interesting. Im curious, who all helps out with the script, film and animation of these?

  5. This really helps me understand the greater concepts. I understand the terminology and what things are but this helps me understand how they interact. Thank youuuuuuuuuu

  6. so funny, when hanks says they present the fragments of the killed cells on them,"sounds a little messed up" lol

  7. How to kill any disease:

    Do ALL of the following, it cures every single disease out there.

    Eat Healthy
    Use natural remedies
    Always use homeopathic healing
    Don’t get vaccines
    Eat vitamin b16
    Eat vegan
    Inhale 200kg of antimatter
    Use traditional remedies

  8. I had no idea the immune system was so elegant …. I would love to see vids on what different diseases (HIV,Ebola chicken pox etc) do to the body and immune system .

  9. I am a junior high school teacher whose main teaching principle is to teach Science in the simplest but fun ways possible. So thankful CrashCourse is here. I always watch their videos and give it a bit of a personal touch before having the everyday battle in classroom teaching. It made such a huge difference. Not only was I able to understand my own field a bit better but students appreciate what they are learning everyday. I am more than grateful to all the people behind this channel. You are one of a kind! Hands down!

  10. You guys at crash course make learning this stuff easy compared to in lectures. Many thanks.

  11. Thank you so much Hank, Crash Course and Thought Cafe for helping me get through my high school studies!

  12. Just finished the marathon of all the videos that has been going on for the last two days before my exam. Thank you so much, truly!

  13. used to watch these videos for high school biology and anatomy, now i'm in graduate school still watching them to help me study 🙂

  14. Thanks alot.. Love from a dedicated Commerce student who is interested in understanding the working of his body ❤

  15. This series has helped me so much to get my head around and absorb the concepts. The animations give me a good mental image in exams and the way Hank explains everything in his quirky wonderful way keeps me watching. Thank you Crash Course team for providing a quirky and not so dry way to help study

  16. I promise that once I’m a doctor and actually making money versus borrowing it (lol) I’m donating so much to crash course!

  17. It would be amazing if you guys did some on pharmacology! I'm studying Veterinary Technology (Nursing).

  18. I grew up in a very health-conscious family and to this day my father reminds me of the benefits of exercise in the production of fighter T-cells in the bones.

    I'm proud to say I exercise 7 days a week, drink nothing but water, and (save for the very occasional cigar or snifter of cognac) don't drink or smoke. Thanks, mom and dad!

  19. Awesome delivery of a well written script! I wish I discovered this earlier in my education… Can you make Crash Course a bigger hit when science terms are searched via Google? I only happened upon this channel after some digging.

  20. If anyone wants to learn about the immune system watch cells at work it helped me learn all the names of the immune cells

  21. thanks for helping me get through 6 years of pharmacy school 😀
    crash course is honestly so much better than the school lectures that I paid over 40k per year

    I live the sarcasm, the jokes, the information, I mean what is there not to love about all your videos!

  23. Plzzzz, also make series of college level biology…and other things

    You guys are doing a very noble and great job😊😊😊

  24. I want to ask a question: Why does ebola virus really dangerous? Why can't it be eradicated in a couple of days like the flu? Like isn't it a type of virus aswell?

  25. You have no idea how much you videos have helped me prepare for exams!! You and your crew are geniuses! Love the animations they help consolidate all the info. Keep up the amazing work!

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