00:00:03
despite being surrounded by harmful
00:00:05
organisms toxins and the threat of our
00:00:07
own cells turning into tumor cells
00:00:09
humans manage to survive thanks largely
00:00:12
to our immune
00:00:13
system the immune system is made up of
00:00:16
organs tissues cells and molecules that
00:00:19
all work together to generate an immune
00:00:21
response that protects us from
00:00:23
microorganisms removes toxins and
00:00:25
destroys tumor cells hopefully though
00:00:28
not all at once the immune response can
00:00:30
identify a threat mount an attack
00:00:33
eliminate a pathogen and develop
00:00:35
mechanisms to remember the offender in
00:00:37
case you encounter it again all within
00:00:39
10 days in some cases like if the
00:00:42
pathogen is particularly stubborn or if
00:00:45
the immune system starts attacking
00:00:47
something it shouldn't like your own
00:00:48
tissue it can last much longer for
00:00:51
months to years and that leads to
00:00:53
chronic
00:00:55
inflammation your immune system is like
00:00:57
the military with two main branches
00:01:00
the innate immune response and the
00:01:02
Adaptive immune response the innate
00:01:04
immune response includes cells that are
00:01:06
non-specific meaning that although they
00:01:09
distinguish an Invader from a human cell
00:01:11
they don't distinguish one Invader from
00:01:13
another Invader the innate response is
00:01:15
also feverishly fast working within
00:01:18
minutes to hours get it feverishly
00:01:21
that's cuz it's responsible for causing
00:01:23
fevers the trade-off for that speed is
00:01:25
that there's no memory associated with
00:01:27
innate responses in other words the
00:01:30
innate response will respond to the same
00:01:32
pathogen in the exact same way no matter
00:01:35
how many times it sees the
00:01:37
pathogen the innate immune response
00:01:39
includes things that you might not even
00:01:40
think of as being part of the immune
00:01:42
system things like chemical barriers
00:01:44
like Lymes in the tears and a low PH in
00:01:47
the stomach as well as physical barriers
00:01:50
like the epithelium in the skin and gut
00:01:52
and the cyia that line the Airways to
00:01:54
keep Invaders out in contrast the
00:01:57
Adaptive immune response is highly
00:01:59
specific for for each Invader the cells
00:02:01
of the Adaptive immune response have
00:02:03
receptors that differentiate one
00:02:04
pathogen from another by their unique
00:02:07
Parts called
00:02:09
antigens adaptive immunity is also
00:02:11
diverse meaning it can recognize almost
00:02:14
an infinite number of specific antigens
00:02:17
and mount a specific response against
00:02:19
each of them the trade-off is that the
00:02:21
Adaptive response relies on cells being
00:02:24
primed or activated so they can fully
00:02:26
differentiate into the right kind of
00:02:27
fighter to kill that pathogen and that
00:02:30
can take a few weeks but the great
00:02:32
advantage of the Adaptive immune
00:02:33
response is immunologic memory the cells
00:02:36
that are activated in the Adaptive
00:02:38
immune response undergo clonal expansion
00:02:41
which means that they massively
00:02:42
proliferate and each time the Adaptive
00:02:44
cells see that same pathogen they
00:02:47
massively proliferate again resulting in
00:02:49
a stronger and faster response each time
00:02:52
that pathogen comes around once that
00:02:54
pathogen is destroyed most of the
00:02:56
clonally expanded cells die off and
00:02:59
that's called clonal deletion but some
00:03:01
of the clonally expanded cells live on
00:03:03
as memory cells and they're ready to
00:03:05
expand once more if the pathogen ever
00:03:09
resurfaces now it's time to meet the
00:03:11
soldiers which are the white blood cells
00:03:13
or lucaites
00:03:14
hematopoesis is the process of forming
00:03:17
white blood cells as well as red blood
00:03:19
cells and platelets and it primarily
00:03:21
takes place in the bone marrow
00:03:23
hematopoesis starts with a multi- potent
00:03:26
hematopoetic stem cell which can develop
00:03:28
into various cell types its future is
00:03:31
undecided some become myoid progenitor
00:03:33
cells whereas others become lymphoid
00:03:36
progenitor
00:03:38
cells the myoid progenitor cells develop
00:03:41
into myoid cells which include
00:03:43
neutrophils eosinophils basophils masted
00:03:47
cells dendritic cells macroasia and
00:03:52
monocytes all of which are part of the
00:03:54
innate immune response and can be found
00:03:56
in the blood as well as in the tissues
00:03:58
the neutrophils eosinophils and
00:04:00
basophils are considered granulocytes
00:04:03
because they contain granules in their
00:04:05
cytoplasm and neutrophils in particular
00:04:07
are also referred to as
00:04:09
polymorphonuclear cells or pmns because
00:04:12
their nuclei contain multiple loes
00:04:14
instead of being
00:04:16
round during an immune response the bone
00:04:19
marrow produces lots of cells many of
00:04:21
which are nutrifil neutrophils use a
00:04:24
process called phagocytosis that's where
00:04:26
they get near pathogen and reach around
00:04:28
it with their cytoplasm to swallow it
00:04:30
whole so that it ends up in a fagone
00:04:33
from there the neutrophils can destroy
00:04:34
the pathogen using two methods they can
00:04:37
use their cytoplasmic granules or
00:04:39
oxidative burst first the cytoplasmic
00:04:42
granules Fus with a phagosome to form
00:04:44
the fago liome the granules contain
00:04:46
molecules that lower the pH of the fagal
00:04:48
liome making it very acidic and that
00:04:51
kills about 2% of the
00:04:53
pathogens now the neutr fill doesn't
00:04:56
stop there it keeps swallowing up more
00:04:58
and more path pathogens until it's full
00:05:00
of pathogens and at that point it
00:05:03
unleashes the oxidative burst during an
00:05:06
oxidative burst the neutr produces lots
00:05:09
of highly reactive oxygen species like
00:05:11
hydrogen peroxide these molecules start
00:05:14
to destroy nearby proteins and nucleic
00:05:16
acids within the phagolysosomes which
00:05:19
are the components of the pathogen that
00:05:21
has been ingested the net result is that
00:05:23
the pathogen is
00:05:25
eliminated now in comparison to
00:05:27
neutrophils eosinophils and basophils
00:05:30
are far less common they both contain
00:05:32
granules that contain histamine and
00:05:34
other pro-inflammatory molecules
00:05:37
eosinophils stained pink with the D
00:05:39
eosin which is where they get their name
00:05:41
they are aiic cells even though it's
00:05:43
not their primary mechanism of attack
00:05:46
they are best known for fighting large
00:05:48
and unwieldy helic parasites or worms by
00:05:51
releasing molecules that can poke holes
00:05:53
in the outer layer of helmets these
00:05:55
cells are also involved in allergic
00:05:57
reactions such as atopic dermatitis and
00:06:00
allergic rinitis also known as hay fever
00:06:03
when involved in allergic reactions
00:06:05
eosinophils degranulate meaning they
00:06:08
release various enzymes and proteins
00:06:09
within their granules and this causes an
00:06:12
inflammatory
00:06:13
reaction next you have basophils and
00:06:16
they stain blue with the di hematoxylin
00:06:19
and unlike neutrophils basophils are
00:06:21
non- aidic on the flip side they
00:06:24
have granules that contain histamine and
00:06:26
other pro-inflammatory molecules
00:06:29
therefore they are important in
00:06:30
initiating allergic
00:06:32
responses finally there are the masted
00:06:35
cells which live in tissues not in the
00:06:37
blood and they're very similar to
00:06:39
basophils they are also non- aiic
00:06:42
and are involved in allergic
00:06:45
responses next up are the monocytes
00:06:47
macrofagos and dendritic cells which are
00:06:50
also aiic cells they gobble up
00:06:53
pathogens present antigens and release
00:06:55
cyto which are tiny molecules that
00:06:58
attract other immune cells to to the
00:06:59
area monocytes only circulate in the
00:07:02
blood some monocytes migrate into
00:07:05
tissues and differentiate into macras
00:07:07
which remain in tissues and aren't found
00:07:09
in the blood dendritic cells are the
00:07:11
prototypical antigen presenting cell
00:07:14
dendritic cells are usually found in
00:07:16
sites that are in contact with most
00:07:17
external antigens like the skin
00:07:19
epithelium or the gastrointestinal
00:07:22
mucosa when dendritic cells are young
00:07:24
and immature they're excellent at
00:07:27
phagocytosis constantly eating large of
00:07:29
protein found in the intial fluid but
00:07:32
when a dendritic cell phagocytose is a
00:07:34
pathogen it's a life-changing Coming of
00:07:37
Age moment mature dendritic cells will
00:07:39
destroy the pathogen and break up its
00:07:41
protein into short amino acid
00:07:44
chains dendritic cells will then move
00:07:46
through the lymph to the nearest lymph
00:07:48
node and they'll perform an antigen
00:07:50
presentation which is where they present
00:07:52
those amino acid chains which are
00:07:54
antigens to te- cells antigen
00:07:57
presentation is what connects the Nate
00:07:59
and adaptive immune systems antigen
00:08:01
presentation is something that can be
00:08:03
done by dendritic cells macrofagos as
00:08:05
well as monocytes which is why all of
00:08:08
these cells are referred to as antigen
00:08:10
presenting cells dendritic cells are the
00:08:13
best of this process because they are
00:08:15
the only cells that live where pathogens
00:08:17
enter through the epithelia like skin
00:08:19
gut and Airways and they are the only
00:08:22
cells that can traffic from these
00:08:23
tissues to lymph nodes where te- cells
00:08:26
circulate now only tea cells with
00:08:29
receptor that can bind to the specific
00:08:31
shape of the antigen will be activated
00:08:33
and that's called priming it's similar
00:08:36
to how a lock will only snap open when a
00:08:38
key with a very specific shape goes in
00:08:41
however te- cells can only see their
00:08:42
antigen if it is presented to them on a
00:08:45
silver platter and on a molecular level
00:08:47
that platter is the major hysto
00:08:49
compatibility complex or MHC for short
00:08:53
so the antigen presenting cell will load
00:08:55
the antigen on an MHC molecule and
00:08:57
display it to t- cells
00:08:59
and when the right t- cell comes along
00:09:01
it
00:09:03
binds the final group of blood cells the
00:09:06
lymphocytes includes B cells t- cells
00:09:10
and natural killer cells B and t- cells
00:09:13
make up the Adaptive immune response
00:09:15
while natural killer cells are part of
00:09:16
the innate immune system B cells and
00:09:19
natural killer cells complete their
00:09:20
development where they started in the
00:09:22
bone marrow whereas some lymphoid
00:09:25
progenitor cells migrate to the thymus
00:09:27
where they develop into tea cells
00:09:30
all of the lymphocytes are able to
00:09:31
travel in and out of tissue and the
00:09:35
bloodstream natural killer cells are
00:09:37
large lymphocytes with granules and they
00:09:39
target cells infected with intracellular
00:09:41
organisms like viruses as well as cells
00:09:45
that pose a threat like cancer cells
00:09:47
natural killer cells kill their target
00:09:49
cells by releasing cytotoxic granules
00:09:52
these granules contain molecules that
00:09:55
punch holes in the Target cell membrane
00:09:57
by binding directly to the phospholipids
00:09:59
and and creating pores and release some
00:10:01
molecules that get inside the cell and
00:10:03
cause target cells to undergo apoptosis
00:10:06
which is a type of program cell
00:10:09
death B cells like t- cells also have a
00:10:13
receptor on their surface that allows
00:10:15
them to only bind to an antigen that has
00:10:17
a very specific shape the main
00:10:19
difference is that B cells do not need
00:10:22
antigens to be presented to them on an
00:10:24
MHC molecule they can simply bind to an
00:10:27
antigen directly when a B cell binds to
00:10:30
a protein antigen that's on the surface
00:10:31
of a pathogen it's capable of
00:10:33
internalizing that antigen degrading it
00:10:36
and presenting it to te- cells so
00:10:38
technically they're also antigen
00:10:40
presenting cells as well like other
00:10:43
antigen presenting cells the B cell
00:10:45
loads the antigen onto an MHC molecule
00:10:48
called mhc2 and displays it to t-
00:10:52
cells when a T Cell gets activated it
00:10:55
helps the B cell mature into a plasma
00:10:57
cell and a plas plasma cell can secrete
00:11:00
lots and lots of
00:11:02
antibodies typically it takes a few
00:11:04
weeks for antibody levels to Peak the
00:11:07
antibodies or immunoglobulins have the
00:11:09
exact same antigen specificity as the B
00:11:12
cell they came from antibodies are just
00:11:14
the B cell receptor in a secreted form
00:11:16
so they can circulate in the plasma
00:11:18
which is the non-cellular part of blood
00:11:21
attaching to pathogens and tagging them
00:11:23
for Destruction because antibodies
00:11:25
aren't bound to cells and Float freely
00:11:27
in the blood this is considered Ed
00:11:29
humoral immunity a throwback to the term
00:11:32
humors which refers to body
00:11:35
fluids now the final type of lymphoid
00:11:37
cell is the te- cell and it's in charge
00:11:39
of cell mediated immunity te- cells are
00:11:42
antigen specific but they cannot secrete
00:11:45
their antigen receptor a naive te- cell
00:11:48
can be activated or primed to allow it
00:11:50
to turn into a mature te- cell by any of
00:11:53
the antigen presenting cells but most
00:11:55
often it's done by a dendritic cell now
00:11:58
there are two main types of t- cells CD4
00:12:00
T cells and cd8 T cells where CD stands
00:12:04
for cluster of differentiation there are
00:12:07
hundreds of CD markers in the immune
00:12:09
system and these CD markers are useful
00:12:11
in telling different cells apart for
00:12:13
example all T cells are CD3 positive
00:12:16
because CD3 is part of the T Cell
00:12:18
antigen receptor so CD4 positive t-
00:12:21
cells are actually CD3 positive CD4
00:12:24
positive and these cells are called
00:12:26
helper cells because they're like
00:12:28
minerals on the battlefield they secrete
00:12:30
cyto kindes that help coordinate the
00:12:32
efforts of macroasia and B cells helper
00:12:35
T cells can only see their antigen if
00:12:37
it's presented on an mhc2 molecule cd8
00:12:40
positive t- cells are CD3 positive cd8
00:12:44
positive and they're called cytotoxic
00:12:46
te- cells because they kill target cells
00:12:49
really similarly to how natural killer
00:12:50
cells do it with one major difference
00:12:53
cd8 positive T cells only kill cells
00:12:56
that present a specific antigen on an
00:12:58
MHC c 1 molecule which is structurally
00:13:01
similar to the mhc2 molecule whereas
00:13:03
natural killer cells aren't nearly as
00:13:05
specific in who they
00:13:07
kill so now let's go through a complete
00:13:10
immune response with the bacterial
00:13:11
pathogen in the
00:13:13
lungs to start the bacteria will have to
00:13:16
get breathed in slip by your nose hairs
00:13:19
past the Celia in the Airways and will
00:13:21
then have to penetrate past the
00:13:22
epithelium layer of the lungs once it's
00:13:25
in the lung tissue the bacteria will
00:13:27
start to divide and might encounter a
00:13:29
resonant macras in the lung tissue which
00:13:31
will ingest the bacteria and start
00:13:33
releasing cyto kindes those cyto kindes
00:13:36
start the inflammatory process by making
00:13:39
blood vessels leaky and attracting
00:13:41
nearby eosinophils basophils and masted
00:13:43
cells which release their own cyto
00:13:45
kindes and granules amplifying the
00:13:47
inflammation nutrifil from the blood as
00:13:50
well as fresh new ones from the bone
00:13:52
marrow dive into the tissue and join the
00:13:54
battle if the pathogen was a virus
00:13:57
natural killer cells would would help
00:13:59
destroy the infected cells at this point
00:14:01
this is all part of the innate immune
00:14:04
response around this point in the
00:14:06
infection immature dendritic cells
00:14:08
residing under the epithelium digest the
00:14:11
pathogens and move from the lung tissue
00:14:13
over to a nearby lymph node where they
00:14:15
present the processed antigen on an mhc2
00:14:18
protein to a naive tea cell the
00:14:21
dendritic cell which is part of the
00:14:23
innate immune response Bridges the
00:14:25
innate and the Adaptive immune responses
00:14:28
when it presents the antigen to the te-
00:14:29
cell which is part of the Adaptive
00:14:31
immune
00:14:32
response sometimes if the infection is
00:14:35
spreading bacteria might find its way to
00:14:37
a lymph node without the help of a
00:14:39
dendritic cell in this case b cells part
00:14:42
of the Adaptive immune response might
00:14:45
directly phagocytose the bacteria and
00:14:47
present it to a naive CD4 positive t-
00:14:50
cell either way if the antigen is the
00:14:52
right fit for the te- cell the te- cell
00:14:54
will begin to differentiate and undergo
00:14:57
clonal expansion differentiated CD4
00:14:59
positive t- cells will release cyto
00:15:02
kindes that will induce B cells to
00:15:04
differentiate into plasma cells which
00:15:06
secrete antibodies that will go into the
00:15:07
lymph and then into the bloodstream the
00:15:10
antibodies will tag pathogens making it
00:15:12
easier for the fago sites to eat them
00:15:14
some cyto kindes will activate macras to
00:15:17
kill bacteria that have been but
00:15:19
cannot be killed by the maccrage alone
00:15:21
unless it gets help from its friends the
00:15:24
tea cells of course if the pathogen was
00:15:26
a virus living and replicating in the
00:15:28
cyop plasma of the infected cells the
00:15:30
cd8 positive T cells would kill any
00:15:32
infected cells that Express the viral
00:15:34
antigen on an
00:15:36
mhc1 over time as the invading pathogen
00:15:39
dies off most of the BNT cells die of
00:15:42
neglect but a few turn into memory B
00:15:44
cells and memory t- cells which linger
00:15:47
for years in case they're needed in the
00:15:50
future all right as a quick recap the
00:15:53
immune system has an innate and an
00:15:55
Adaptive response the innate immune
00:15:57
response is immediate iate but
00:15:59
non-specific and lacks
00:16:01
memory whereas the Adaptive immune
00:16:03
response is highly specific and
00:16:05
remembers everything but it takes
00:16:07
several days to get started and almost
00:16:10
two weeks to
00:16:14
Peak helping current and future
00:16:17
clinicians Focus learn retain and Thrive
00:16:20
learn
00:16:27
more
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