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What’s true in World of Warcraft is also
true in your immune system:
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To defeat your enemy, you have to know your
enemy.
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Uncover its weaknesses. Learn how to see it,
before it sees you.
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We’ve already talked about how your innate
defense system keeps out, or quietly neutralizes,
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pathogens without much too much fuss. But
sooner or later, a threat’s gonna come along
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that’s stronger than what the first-responders
can handle. That’s when it’s time for
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the adaptive, or acquired immune system to
step in.
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While your innate system takes its zero-tolerance
policy very seriously, and tries to toast
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any foreign microbe that it encounters, your
adaptive system does things differently.
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It has to be expressly introduced to a specific pathogen,
and recognize it as a threat, before it will attack.
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As its name suggests, you’re not born with
a working adaptive immune system -- it’s
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slow to act, in part because it takes time
for it to shake hands with so many pathogens
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and get to know them.
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These introductions may be organic -- like
touching a dirty faucet in the bathroom or
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walking into a sneeze cloud.
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Or they may be premeditated, which is why
vaccination is pretty much the greatest thing
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to happen to medicine ever.
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But once it’s been introduced to a potential
threat, your adaptive defenses never forget
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it. And this ability to remember specific
pathogens is one of the key differences between
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the adaptive and innate defenses.
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Another main difference is that adaptive immunity
is systemic -- rather than being restricted
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to a particular infection in, say, a sinus
or a sliced finger, your adaptive system can
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fight throughout your whole body at once.
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And it does this by deploying one or both
of its separate, but cooperating, defenses
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-- your humoral immunity and your cellular
defenses.
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Your humoral immunity -- which you might not
have heard of before -- works by dispatching
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important proteins that I’m sure you have
heard of: antibodies.
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They’re made by special white blood cells,
and they patrol the body’s “humors”
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or fluids like blood and lymph, where they
combat viruses and bacteria moving around
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the interstitial space between your cells.
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Much of what you know, or have heard about,
or think of, when your immune system comes
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up actually has to do with your humoral immunity.
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It’s why, if you had mumps as a kid, you
probably don’t have to worry about getting
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it again for the rest of your life.
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It’s also why doctors and nurses and patients
who have been infected with the ebola virus
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-- a disease once thought to be incurable
-- have lived to tell about it.
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And it’s why vaccinations work.
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Whether you’re protecting yourself from
infections or playing an MMO, one of the first
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steps in any good defensive strategy is to
be able to tell your friend from your foe.
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And in the case of your immune system, that
means being able to identify antigens.
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An antigen could be an invader from the outside
world, like a bacterium, virus, or fungus.
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Or it could be a toxin or a diseased cell
within your own body.
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But in any case, antigens are large signalling
molecules not normally found in the body,
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and they act as flags that get the adaptive
immune system riled up.
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So let’s say a flu virus gets inside of
you, and it’s floating around trying to
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find a good host cell to start multiplying
inside of.
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Before it finds that cell, hopefully it will
be paid a visit by one of the stars of your
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humoral response -- a B lymphocyte.
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Like all blood cells, these guys originate
in your bone marrow. But unlike other white
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blood cells, they also mature in the bone
marrow too.
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And as a B cell matures, it develops the ability
to determine friend from foe, developing both
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immunocompetence -- or how to recognize and
bind to a particular antigen -- as well as
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self-tolerance, or knowing how to NOT attack
your body’s own cells.
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Once it’s fully mature, a B lymphocyte displays
at least 10,000 special protein receptors
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on its surface -- these are its membrane-bound
antibodies.
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All B lymphocytes have them, but the cool
thing is, every individual lymphocyte has
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its own unique antibodies, each of which is ready
to identify and bind to a particular kind of antigen.
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That means that, with all of your B lymphocytes
together, it’s like having 2 billion keys
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on your immune system’s keychain, each of
which can only open one door.
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So, part of your immune system’s strategy
is just to win with overwhelming odds: The
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more unique antibodies your lymphocytes have,
the more likely it is that one will eventually
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find, bind to, and mark a particular antigen.
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Once they’ve matured, B cells colonize or
“seed” your secondary lymphoid organs,
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like your lymph nodes, and start roaming around
in your blood and lymph.
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At this point they’re still naive and untested,
and they won’t truly be activated until
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they meet their perfect enemy match.
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Which brings us back to the flu virus.
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When the right B cell finally bumps into an
antigen it has antibodies for -- usually in
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a lymph node or in the spleen -- and recognizes
it, it binds to it. This summons the full
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power of the humoral immune response, and
the cell basically goes into berserker mode.
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Once activated, the B cell starts cloning
itself like crazy, quickly producing an army
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of similar cells, all with the instructions
for the exact same antibodies that are designed
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to fight that one particular antigen.
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Most of these clones become active fighters,
or effector cells. But a few become long-lived
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memory cells that preserve the genetic code
for that specific, successful antibody.
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This ensures that, if and when the antigen
returns, there will be a prepared secondary
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immune response that’s both stronger and
faster than the first.
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This is key to why vaccinations are so brilliant
and important, which I’ll come back to in a minute.
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But while the memory cells are just there
to hang back and record things, the effector,
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or plasma cells, are packed with extra amounts
of rough endoplasmic reticulum, which acts
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as an antibody factory.
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These cells can mass-produce the same antibodies
over and over for that particular invader,
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spitting them out into the humor at a rate
of around 2,000 antibodies per second for
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four or five days until they die.
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And the antibodies they make work the same way that
the membrane-bound ones do; they’re just free-floating.
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So they ride the tides of blood and lymph,
binding to all the antigens they can find,
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and marking them for death.
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Now, antibodies can’t really do the killing
themselves, but they do have a few moves that
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could make it hard for intruders to take hold.
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One of their most effective and common strategies
is neutralization, where antibodies physically
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block the binding sites on viruses or bacterial
toxins, so they can’t hook up to your tissues.
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And because antibodies have more than one
binding site, they can bind to multiple antigens
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at the same time, in a process called agglutination.
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The resulting clumps can’t get around easily,
which makes it easier for macrophages
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to come and gobble them up.
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And not only that, but while all this is going
on, antibodies are also ringing a chemical
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dinner bell, calling in phagocytes from the
innate immune system, and special lymphocytes
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from the adaptive system, to destroy these
messy little antigen-antibody clumps.
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So, the point of all this in the short term
is to keep you healthy. But in the long term,
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this process also adds to your overall immunity.
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The humoral response allows your body to achieve
immunity by encountering pathogens either
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randomly or on purpose.
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Active humoral immunity is what we were just
talking about -- it’s when B cells bump
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into antigens and start cranking out antibodies.
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This can occur naturally, like when you catch
the flu or get chickenpox or pick up some
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nasty bacterial infection, or it can happen
artificially -- particularly through vaccination.
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Most vaccines are made of a dead or extremely
weakened pathogen. And they work on the premise
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that, because a secondary immune response
is more intense than a primary response, by
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introducing a pathogen into your body, you’re
priming it to fight hard and fast should that
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antigen show up again.
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In the case of typically non-fatal infections,
like the common flu, this immunity should
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at least spare you from some of the most severe
symptoms.
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But in the case of more serious diseases,
like polio, smallpox, measles, and whooping
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cough, vaccinations can be truly life-saving.
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Now, some antigens -- like those for mumps
or measles -- don’t really change much over
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time, so a few immunizations will leave you
set for life.
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But others, like influenza, are constantly
evolving and changing their surface antigens.
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So immunity to last year’s flu probably
doesn’t work against this year’s flu.
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Still, acquired immunity doesn’t have to
be active.
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Babies, for example, naturally obtain passive
humoral immunity while still in the womb.
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They receive readymade antibodies from their
mothers through the placenta, and later on
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through breast milk.
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And that works pretty well for a few months,
but the protection is temporary, because passively
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obtained antibodies don’t live long in their
new body. And they can’t produce effector
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cells or memory cells, so a baby’s own system
won’t remember an antigen if it gets infected again.
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You can also acquire this kind of temporary
passive immunity artificially, by receiving
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exogenous antibodies from the plasma of an
immune donor.
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This is what recently saved some doctors and
nurses who had contracted the ebola virus
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from infected patients.
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A serum was made from the blood plasma of
other medical workers who had been infected,
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and survived.
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The antibodies helped defend the patients
from the virus before their own active immunity
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could identify that particular antigen and
start creating their own antibodies.
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It’s not the same as a vaccine, which immediately
engages your B cells, but it can buy a patient
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some crucial, life-saving time against an
infection that would otherwise quickly kill.
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But B cells and antibodies are only part of
the immunity equation. There are plenty of
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pathogens that quickly worm their way right
inside your cells, where they’re safer from
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the humoral response and free to multiply
as much as they’d like.
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Luckily, your immune system has yet another
game plan and new set of players ready to
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fight that final battle with cell to cell
combat.
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Make sure you catch our final episode next
week and learn all about this epic battle royale.
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But as for today, in our second-to-last episode,
you learned how the adaptive immune system’s
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humoral response guards your extracellular
terrain against pathogens. We looked at how
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B cells mature, identify antigens, and make
antibodies, and how antibodies swarm pathogens
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and mark them for death. We also talked about
active and passive humoral immunity, and how
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vaccines work.
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Thank you to our Headmaster of Learning, Linnea
Boyev, and thank you to all of our Patreon
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patrons. If you are one of those people I
just thanked, you make Crash Course possible,
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for the whole world and also for yourself.
If you like Crash Course and you want to help
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us make videos like this one, you can go to
patreon.com/crashcourse.
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This episode was filmed in the Doctor Cheryl
C. Kinney Crash Course Studio, it was written
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by Kathleen Yale. The script was edited by
Blake de Pastino. Our consultant is Dr. Brandon
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Jackson. It was directed by Nicholas Jenkins,
edited by Nicole Sweeney, our sound designer
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is Michael Aranda, and the Graphics team is
Thought Cafe.
