Vaccines are possibly the greatest thing that humans ever created.
Not just in the realm of medicine, but like all of human creation.
Space travel is awesome.
Agricultural revolution? For the most part, pretty sweet.
The entirety of YouTube? Up there
but maybe not as lifesaving as vaccination.
Vaccinations has its root in variolation,
a technique developed by Asian physicians prior to the 1700s.
They would take dust from someone’s smallpox scab
and blow it into their patient’s nose
the patient would experience a weaker version of smallpox,
but then they’d be immune to it for life.
Variolation was far from perfect, and just sounds gross,
but when the alternative is contracting a potentially fatal version of smallpox,
it was a good first step.
In the hundreds of years since,
doctors have made huge advances in vaccination technology,
like Edward Jenner’s famous smallpox vaccine made from cowpox virus,
or Louis Pasteur’s vaccines against rabies and anthrax.
But here’s the thing,
all of these revolutionary concepts in science came before we knew
how our immune system worked on a cellular level.
So today, we’re going to go through the story of early immunology
to learn how they figured out the cells of the immune system.
Around the same time as Pasteur,
a Russian researcher named Elie Metchnikoff was studying starfish larvae
and noticed that certain cells would engulf foreign objects.
He called these cells phagocytes, which meant devouring cells.
This seemed like a viable explanation for how immunity worked.
Our cellular defenses gobbled up potential threats.
But during the development of the diphtheria vaccine,
another idea was put forward.
German scientist Paul Ehrlich hypothesized that there was
some kind of anti-toxin floating in the blood that would confer immunity.
These would later become known as antibodies.
So by the end of the 19th century,
scientists knew that germs caused disease,
that substances in the blood could confer immunity,
and that cells could swallow up pathogens.
But we still had some big questions to answer.
Specifically, there were two schools of thought regarding how immunity works.
On one team were the “cellularists”,
who thought that free floating phagocytes were more important to immunity than antibodies.
This became known as cellular immunity.
On the other team were the “humoralists”
who believed in humoral immunity. To them,
clearly something dissolved in the blood had to mediate immunity.
So to start with,
your body has an immune system that keeps you safe from pathogens,
anything that causes disease like a bacteria, parasite, or virus.
病原体指任何会引起疾病的东西 如细菌 寄生虫或病毒
Those researchers at the end of the nineteenth and start of the twentieth century
were debating two types of immunity
that we now know are both present in our bodies
From 1900 to the 1940s,
it seemed like the humoralists had a better case.
Experiment after experiment showed that antibodies conferred immunity.
Plus, scientists were zeroing in on
how antigens hook up to antibodies and antibodies’ structure.
But the importance of the humoral theory was challenged
during a major experiment in 1942,
by our old friend Karl Landsteiner,
that dude discovered ABO blood types,
and his colleague Merrill Chase.
还有 他的同事Merrill Chase
They took one set of guinea pigs and gave them the tuberculosis bacteria,
which meant they would build antibodies and thus immunity to TB.
Then they injected the blood serum with TB antibodies
into naive guinea pigs, or non-immunized guinea pigs,
and later exposed them to the TB antigen.
But the immunity transfer didn’t work.
So maybe antibodies weren’t the only thing conferring immunity?
Chase next tried to immunize his guinea pigs with a new solution,
which accidentally contained lymphocytes,
white blood cells that play a huge role in our immunity.
When the research team looked under the microscope,
they saw these immune cells at work,
which strengthened the cellular immunity theory.
We had way more questions though.
Like, if there are millions and millions of types of pathogens out there
how does our immune system make antibodies for all of them?
There was no way millions of species of cells
were built into our bodies for millions of antigens.
so we must have to manufacture antibodies after being exposed to the pathogen.
This gave rise to something in the late 50s called clonal selection theory,
which, as the name suggests, implies clones, or copies of cells.
First, humans along with other animals have immune cells called lymphocytes.
They’re a thing that exist and have a name by this point.
淋巴细胞 在那个时代已经被发现 并进行了命名
Lymphocytes respond to antigens according to receptors on the lymphocyte’s surface.
When that lymphocyte gets in contact with its appropriate antigen,
it will proliferate, or clone itself.
From there, the clones will either secrete antibodies
or recruit more cells to respond to the pathogen.
But that still didn’t show us how lymphocytes recognize antigens themselves.
Then, in the early 1960s,
scientists started paying more attention to an organ called the thymus,
an organ in the lymphatic system
which until then, wasn’t completely understood.
So a scientist named Jacques Miller removed the thymus from infant mice
and noticed that the mice developed more severe infections
and mounted weaker antibody responses.
So that seemed like some easy math
Take out the thymus and the immune system weakens.
But how exactly the thymus supported immunity was still a mystery.
但是 胸腺究竟是如何对免疫力有帮助的 仍然是一个谜
By this point,
scientists knew that cells in the bone marrow could make hematopoietic stem cells,
those types of cells that can become any type of blood cell.
So maybe lymphocytes started in bone marrow and mature in the thymus.
所以 或许淋巴细胞 只是在胸腺中成熟 而来源处却是骨髓
Enter James Gowans,
who traced lymphocytes all around the body
and found that they went from the blood into lymphatic circulation,
then into lymph nodes, and back into the bloodstream.
This gave us the idea that the thymus manufactured lymphocytes
which then traveled through circulation,
eventually coming to secondary lymphoid organs like lymph nodes.
最终来到 比如淋巴结 这类二级淋巴器官中
Now that we knew where lymphocytes came from,
we could tie that back to the old clonal selection theory.
They got the idea that naive lymphocytes,
or lymphocytes that hadn’t been activated by an antigen yet,
grew up in the thymus.
Then when they were excreted and made it to the lymph nodes,
然后 它们被分泌出来 成功抵达淋巴结后
they would differentiate into fully functioning, antibody-producing plasma cells
depending on which antigen they encountered.
So they were born in the bone marrow but grew up in the thymus.
These thymus derived cells became known as T cells.
Around the same time, separate scientists saw that
lab chickens developed an impaired antibody responsiveness
when they removed their bursa of Fabricius,
a bird-specific lymphatic organ found near their little chicken butts.
That complicated our nice, tidy definition a bit
because that meant that there might be two types of lymphocytes.
Through a series of experiments on chicken embryos,
scientists found that different lineages of lymphocytes developed in the thymus
compared to the chicken’s bursa.
These became known as bursa derived cells, or B-cells,
which mediated humoral immunity.
Thus, the two superstar cells of the adaptive
immune system got their names.
Fun fact, humans do have structures called synovial bursa
but they’re more cushioning for our joints.
So they’re different from the bird version.
That raises another question though.
Humans aren’t birds. Like not even a little bit.
So we don’t have the organ that produces B cells that birds do.
So where do humans make B cells,
and how does the whole immune response work with all these moving pieces?
As it turns out,
B cells both form and mature in the bone marrow itself.
They only start to differentiate
once an antigen hooks up to any of the receptors on its surface.
By now we’re in the 1970s,
and we still had a few things to figure out,
like how the T cells don’t just self destruct and kill our own cells.
See, bacteria infect our bodies differently than viruses.
Bacteria will invade our bodies somehow,
then reproduce by splitting apart into two cells
But viruses get directly into the host’s living cells,
and use their host’s cellular machinery to reproduce,
and eventually burst out of those cells to infect more cells
and keep the process going.
So to keep that virus from hijacking more of your cells,
sometimes your immune system needs to kill off your own cells.
During an experiment published in 1974,
researchers saw how our immune systems could differentiate
our infected cells from other cells.
In it, they gave a virus to a bunch of lab mice,
and swapped T cells from one mouse to another.
The T cells did their normal job as expected.
They’d destroy cells infected with viruses
but, unexpectedly, only if the infected cell
came from the same strain of mice as the T cell.
If a T cell detected that a random cell was infected with a virus,
but it was from some other mouse,
it wouldn’t destroy it.
Basically, T cells showed that
they would only help cells from their same family.
This would become known as self-nonself discrimination.
This was a big development because it showed that
T cells only destroyed foreign cells
if they presented an antigen
and presented a molecule that identified it as a “self” cell.
That identifying molecule was major histocompatibility complex,
or MHC for short,
a molecule that presents the antigen-of-interest to different T cells.
Then in 1978, scientists identified the dendritic cell,
a phagocytic cell that eats up pathogens
and presents its antigen to the other cells,
helping to eventually grant immunity to that pathogen.
That made it an APC, or antigen-presenting cell.
因此被称为APC 或者说 抗原呈递细胞
I have slayed this E coli for you! Behold!
Feast thine eyes upon its carcass!
One of the most recent discoveries in the story of B and T cells
shed some light on how these two types of immune cells work together.
In order for our cells to remember that pathogen,
the APC will present an antigen to one type of T cell
so it can destroy the pathogen,
while another type of T cell will share that antigen with B cells,
which then make antibodies for it.
That development would let us understand
how those early vaccines at the start of the twentieth century worked.
The vaccine itself is a weakened or imitation pathogen
that we administer to people without immunity to that pathogen.
Their bodies respond first by attacking the pathogen,
but then build up a reservoir of memory T cells and antibodies from B cells
to attack that pathogen in the future.
After all those years of not knowing how vaccines were saving lives,
we finally learned how.
Next time, we’ll learn about a major source of those
B and T cells, the lymphatic system.
I hoped you liked this episode of Seeker Human,
I always love these history based episodes. They’re so fun to write.
I’m Patrick Kelly and thanks for watching.
我是Patrick Kelly 感谢收看
Vaccines are possibly the greatest thing that humans ever created.