00:00:01
so in this chapter nine uh we're going
00:00:03
to we're going to talk about
00:00:04
inflammation and Immunity and we're
00:00:06
going to first start out here with the
00:00:08
innate defenses of immunity uh the
00:00:10
innate immune response requires no
00:00:12
previous exposure to effectively respond
00:00:15
to a given antigen and if you all
00:00:18
remember from previous classes uh
00:00:19
antigens are basically a molecule that
00:00:23
can stimulate an immune response and
00:00:25
these antigens could be things like
00:00:27
proteins glycoproteins glycolipids
00:00:30
something that the immune system can
00:00:32
recognize as being
00:00:33
foreign um now the innate defenses
00:00:36
include a series of cells like natural
00:00:38
killer cells which are type of
00:00:39
lymphocyte and other fosic cells so the
00:00:42
cells that can engulf forign debris and
00:00:45
microorganisms including neutrophils and
00:00:48
macras remember the neutrophils are the
00:00:50
most abundant immune cell um in your
00:00:54
white blood cells so then these
00:00:56
neutrophils here um are part of your
00:00:59
inate defense which means your innate
00:01:01
defense is pretty widespread so the
00:01:04
specific defenses differ than the innate
00:01:06
defenses because these specific defenses
00:01:09
respond more effectively upon second
00:01:12
exposure to a particular antigen also
00:01:15
these specific defenses are highly
00:01:17
selective and can only respond to one
00:01:20
antigen um one specific type of antigen
00:01:24
now these specific defenses involve the
00:01:26
B and T lymphocytes which we'll go into
00:01:28
more detail here in a little bit
00:01:30
and um this has to be learned so we talk
00:01:33
about the specific immune defenses as
00:01:36
being learned or adaptive because they
00:01:39
uh develop upon exposure to a new
00:01:43
foreign
00:01:45
antigen now part of our immune defense
00:01:48
relates to different barriers like
00:01:50
epithelial barriers so it turns out that
00:01:53
uh even before your immune cells start
00:01:55
to fight off Foreign debris or
00:01:57
microorganisms your skin and mucus
00:01:59
membranes act as a first line of defense
00:02:02
uh for one reason being that the skin
00:02:04
epithelium here produces molecules
00:02:07
called defensin which can basically
00:02:08
punch holes in bacterial membranes um
00:02:12
and the on top of the fact too that skin
00:02:13
is a really tough and protective barrier
00:02:15
so that bacteria or other microorganisms
00:02:17
can't just wiggle through in between
00:02:19
your skin cells uh the intestinal
00:02:22
epithelium you know along your GI tract
00:02:25
produces cryptdins which are just a
00:02:27
class of molecules that again are
00:02:28
antimicrobial
00:02:30
now uh disruption of these normal
00:02:32
epithelial barriers like disruption of
00:02:34
the skin epithelium or intestinal
00:02:36
epithelium can increase the likelihood
00:02:38
that a pathogen can establish an
00:02:40
infection so you're more likely to get
00:02:41
an infection of skin if there's a wound
00:02:44
in skin you know where that skin
00:02:46
epithelium barrier is now compromised or
00:02:48
an infection of the gut if there's some
00:02:50
sort of ulcer or wound within the gut
00:02:53
mucosal
00:02:54
wall now uh we're going to first talk
00:02:57
about the macras which are part part of
00:02:59
your innate immune response uh these
00:03:02
macroasia are powerful phagocytes and
00:03:05
they clean up dead neutrophils and
00:03:07
inflammatory debris so they basically
00:03:09
help remove any dead tissue or dead
00:03:11
cells and therefore have a role in wound
00:03:14
healing now macroasia again are part of
00:03:17
your innate ammun response and so
00:03:20
they're not specific they can just
00:03:22
remove a wide variety of antigens in
00:03:25
debris and
00:03:27
microorganisms now most of your immune
00:03:30
cells are derived from um the lymphoid
00:03:34
system here and uh it involves a series
00:03:38
of organs like bone marrow and your
00:03:40
thymus gland so we know that bone marrow
00:03:42
especially red bone marrow in particular
00:03:44
has a variety of stem cells that give
00:03:46
rise to all of your white blood cells so
00:03:49
the
00:03:50
lymphocytes and the rest of your immune
00:03:52
cells all come from red bone marrow now
00:03:56
many of these immune cells will develop
00:03:58
uh in different areas of your body
00:04:00
including including bone marrow or your
00:04:02
thymus te- cells in particular develop
00:04:05
in the thymus and the thymus is a large
00:04:07
gland it's most active before puberty
00:04:10
but it's a large gland that sits in the
00:04:12
medyum just Superior to your heart now
00:04:15
the lymphocytes are produced from stem
00:04:17
cells and this includes T and B
00:04:18
lymphocytes now T lymphocytes migrates
00:04:21
migrate to the thymus to develop whereas
00:04:23
B cells and natural killer cells will
00:04:25
stay in your red bone marrow during
00:04:27
development and what I mean by
00:04:28
development is that they need to grow
00:04:31
and become immunocompetent or basically
00:04:34
be able to effectively fight infection
00:04:36
and recognize foreign antigens now there
00:04:40
are other secondary organs like lymph
00:04:42
nodes spleen tonsils and Pyers patches
00:04:44
which you find in your intestin which
00:04:46
are also involved in immune defense
00:04:48
because they contain uh high
00:04:50
concentrations of lymphocytes so you're
00:04:52
going to find a lot of lymphocytes so TB
00:04:54
and natural pillar cells in lymph node
00:04:56
spleen tonsils and pyrus patches so what
00:04:59
this slide is showing is basically just
00:05:01
a general overview of your lymphatic
00:05:03
system and if youall remember from A&P
00:05:05
the lymphatic system is a series of uh
00:05:08
vessels that you find in most tissues of
00:05:11
your body except for bone and teeth but
00:05:13
these lymph vessels will pick up excess
00:05:16
fluid from the tissues and then slowly
00:05:18
carry that excess fluid back towards
00:05:21
your heart where then the the lymph is
00:05:24
then mixed back in with your bloodstream
00:05:26
now what's important to note though with
00:05:27
respect to the immune system is that
00:05:29
your lymphoid system is uh basically
00:05:32
also rich in a lot of lymphocytes or
00:05:34
immune cells so as that excess fluid
00:05:37
gets carried back towards your
00:05:38
bloodstream it's also cleaned up along
00:05:40
the way so if there's any debris or
00:05:42
microorganisms in that fluid uh the
00:05:44
lymphocytes here in lymph nodes and
00:05:46
lymph vessels will help will help clear
00:05:49
those out um ideally before it goes back
00:05:51
in your bloodstream and to the rest of
00:05:53
your body now what this is shown you
00:05:55
guys are this the the main types of Lucy
00:05:58
and Lucy are basically just your white
00:06:00
blood cells now all of these are derived
00:06:02
from stem cells you find in red bone
00:06:04
marrow and the major type of Lucy we
00:06:07
have are the neutrophils lymphocytes
00:06:09
monocytes eosinophils and the basophils
00:06:13
now this show this is actually in order
00:06:15
of their abundance normal abundance in
00:06:18
the bloodstream so normally you should
00:06:20
find 60 to 80% of your white blood cells
00:06:23
are neutrophils 20 to 30% of your white
00:06:25
blood cells are lymphocytes so B cells T
00:06:28
cells and natural killer cells include
00:06:31
the lymphocytes 3 to 8% are monocytes
00:06:34
which include macrophases uh 1 to 6% are
00:06:37
eosinophils and then 0 to 2% are
00:06:39
basophils which are the most are most
00:06:41
uncommon or least abundant now in terms
00:06:44
of just the general functions of each of
00:06:46
these types of Lucy uh the neutrophils
00:06:49
are first to appear after injury and
00:06:52
they're involved with phagocytosis
00:06:54
remember the neutrophils are part of
00:06:56
your innate immune response so they're
00:06:58
not specific nor are they adaptive or
00:07:01
learned they uh more broadly respond to
00:07:05
a lot of different foreign antigens
00:07:07
debris or tissue damage and again these
00:07:09
are the most abundant uh the lymphocytes
00:07:11
include your B cells and t- cells which
00:07:14
are part of your learned or adaptive
00:07:16
immunity or specific immunity and they
00:07:17
respond to one antigen but the
00:07:19
lymphocytes also include natural killer
00:07:21
cells which are part of your innate
00:07:25
immune
00:07:26
response now monocytes are a type of
00:07:28
mobile macras the monocytes are a macras
00:07:32
or big eater that basically float around
00:07:34
the bloodstream and they remain in their
00:07:36
inactive form until they encounter uh
00:07:39
you know infected tissue or inflammation
00:07:41
where these monocytes then can activate
00:07:43
into macras and then enter that infected
00:07:46
or inflamed tissue and then participate
00:07:48
in phagocytosis and if you all remember
00:07:50
from previous slides remember the macras
00:07:52
are part of your specific I'm not
00:07:56
specific I'm sorry they're part of your
00:07:57
innate immune response so the
00:07:59
eosinophils here uh 1 to 6% of your
00:08:02
immune cells these are involved in
00:08:04
allergic reactions and parasitic
00:08:05
infections and so what's interesting is
00:08:07
that these are uh potential targets with
00:08:11
you know allergies and autoimmune
00:08:13
disease because for whatever reason
00:08:15
these cells seem to play a role uh if
00:08:18
they're overactive they seem to play a
00:08:20
role in you know excessive amounts of
00:08:22
allergy even even the autoimmune
00:08:24
response and so there's a there's an
00:08:26
interesting hypothesis out there that
00:08:28
talks about how you can use parasites
00:08:31
possibly to treat Auto autoimmune
00:08:33
disease and we may come back to that
00:08:35
later now the basophils uh have a lot of
00:08:39
histamine granules so they contain a lot
00:08:41
of histamine now histamine is a type of
00:08:43
molecule that's released during the
00:08:45
inflammatory response and during the
00:08:48
allergy response so basophils are
00:08:51
important during um inflammation so if
00:08:55
you inhibit basophils then you inhibit
00:08:57
the release of histamine and therefore
00:08:59
reduce things like allergic reactions or
00:09:01
inflammation and again we'll come back
00:09:03
to these
00:09:05
later so we'll first talk about the
00:09:07
neutrophils here neutrophils remember
00:09:09
the most abundant of the lucites also
00:09:11
called the
00:09:12
polymorphonuclear nucle sites or pmls
00:09:14
now these are important in acute
00:09:16
bacterial infections and they release
00:09:18
toxins like fre rical defensins and
00:09:21
enzymes such as lasas and although these
00:09:24
cells normally help to remove dead and
00:09:27
damaged tissue as well as clar infection
00:09:30
they can also damage normal tissue so
00:09:32
excessive nutrifil activities can also
00:09:35
damage healthy tissue uh near their side
00:09:38
of activity there there's a little bit
00:09:39
of um collateral damage there but you
00:09:42
know it's all it's all in good effort I
00:09:44
guess now the lymphocytes include
00:09:46
natural killer cells T cells and B cells
00:09:48
of these three it's the T and B cells
00:09:51
that are involved with your specific or
00:09:53
learned immune response whereas the
00:09:55
natural killer cells are part of your
00:09:57
innate immune response so meaning they
00:09:59
can respond to many different antigens
00:10:01
and are less specific uh these natural
00:10:04
killer cells you find in circulation and
00:10:06
they can migrate from blood into an
00:10:08
infected tissue when necessary the T
00:10:11
andb cells are lymphocytes that are part
00:10:14
of your specific or adaptive immunity
00:10:17
and they all play different roles in the
00:10:18
immune response so we'll talk about the
00:10:20
the specific types of te- cells that are
00:10:22
involved with immunity as well as the
00:10:24
specific types of B cells that are
00:10:25
involved with immunity but what's
00:10:27
important to note in this slide is that
00:10:29
T cells mature in the thymus B cells
00:10:31
mature in bone marrow so if someone has
00:10:34
damage to the thymus or bone marrow it
00:10:35
can affect the development of these
00:10:38
cells now um there are two major classes
00:10:42
of t-lymphocytes and remember the T
00:10:44
lymphocytes are part of your specific
00:10:47
adaptive or learned immune response so
00:10:50
these two major classes include the t-
00:10:52
helper and sat toxic tea cells uh it's a
00:10:54
t- helper cells that are have CD4
00:10:57
proteins uh these have a function or
00:11:00
role in activating other te- cells and
00:11:02
macrophases they can also stimulate B
00:11:05
cells um by releasing inflammatory cyto
00:11:08
so when these helper t- cells release
00:11:10
cyto it can activate B cells to release
00:11:13
we call antibodies and we'll come back
00:11:15
to that
00:11:16
later so think about the te- cells in
00:11:19
the immune response is it's sort of like
00:11:20
the cheerleaders of the immune response
00:11:22
you know they don't participate directly
00:11:24
in fighting infection rather they can
00:11:27
release a lot of cyto kindes when they
00:11:31
recognize infection or tissue damage
00:11:33
that can activate other immune cells so
00:11:36
these T helper cells once they release
00:11:38
cyto they can go on and activate things
00:11:40
like cytotoxic te- cells or even the B
00:11:43
cells which we'll talk about soon now
00:11:45
the cytotoxic te- cells are cd8 positive
00:11:48
and they do function in killing off uh
00:11:51
particular cells that contain certain
00:11:54
antigens however these satox te- cells
00:11:57
require signals or satchin to be
00:12:00
released by the t- helper cells in order
00:12:02
to function normally now the CD4
00:12:05
proteins and cd8 proteins you find on
00:12:07
cytotoxic te cells uh these are
00:12:09
important types of proteins uh involved
00:12:12
with recognizing foreign antigens but
00:12:14
what's interesting about these CD4
00:12:16
proteins is that HIV human imuno
00:12:19
deficiency virus only infects cells that
00:12:21
are CD4 positive so specifically it's
00:12:24
the t- helper cells that are affected
00:12:26
during the uh HIV infection
00:12:29
so if HIV infects t- helper cells
00:12:32
basically what HIV is doing is
00:12:34
diminishing your immune system's ability
00:12:36
to get the rest of the immune system
00:12:38
excited because now there's less t-
00:12:41
helper cells to release pro-inflammatory
00:12:44
pyocin which means that other immune
00:12:46
cells like your cytotoxic tea cells or B
00:12:48
cells are less responsive to infection
00:12:51
and that's a sort of Insidious thing
00:12:54
about uh HIV infection so the B
00:12:57
lympocytes are also part part of your
00:12:59
specific adaptive or learned immune
00:13:02
response and they have antibod like
00:13:04
receptors on their cell
00:13:05
surface they carry many copies of
00:13:08
identical B cell receptors and like the
00:13:10
t- cells they can only respond to one
00:13:13
type of antigen now these B cells can
00:13:16
produce memory cells so once you form a
00:13:18
certain type of B cell some of the cells
00:13:21
actually will form clones that actually
00:13:23
become inactive and they kind of go
00:13:25
dormant in different areas of your body
00:13:27
that way you have a learn or a memory of
00:13:30
the infection if you ever encounter that
00:13:32
infectious organism again later now many
00:13:35
of these B lympocytes can survive from
00:13:37
months to years which is why upon
00:13:39
subsequent exposure to the same antigen
00:13:42
your immune system can really respond
00:13:44
rapidly to that same antigen it's seen
00:13:47
uh previously now for a typical B cell
00:13:50
you know we got B cell receptors and
00:13:52
they can respond to an antigen now
00:13:54
what's interesting here then is that
00:13:56
once these B cells recognize a foreign
00:13:58
antigen their role then is to really
00:14:01
make antibodies so an activated B cell
00:14:04
will turn into a clone called a plasma
00:14:07
cell which is basically just an antibody
00:14:10
Factory and it starts pumping out
00:14:12
antibodies to attack uh you know foreign
00:14:15
antigens now um some other aspects of
00:14:19
your uh innate immune response include
00:14:22
what we call complement so complement
00:14:24
includes 20 different plasma proteins
00:14:26
which are typically synthesized mostly
00:14:29
by the liver macroasia and nutrifil and
00:14:33
these 20 different plasma proteins have
00:14:35
really important roles in your innate
00:14:37
immune response so they do things like
00:14:39
enhance inflammation they can actually
00:14:42
lice or break apart target cells they
00:14:45
can actually attract other immune cells
00:14:46
to a sight of inflammation or infection
00:14:49
or they can also Target foreign cells
00:14:51
for removal by um you know immune cells
00:14:55
so you can see here that once these uh
00:14:58
complement proteins become activated
00:15:00
they have these specific functions here
00:15:03
and so it's important then that you have
00:15:05
normal liver function macras function
00:15:08
and nutrifil function to make a
00:15:10
sufficient amount of complement proteins
00:15:12
to you know bring this aspect of of the
00:15:16
immune system
00:15:19
in now what this is showing are one of
00:15:21
the complement Cascades and to me this
00:15:23
is one of the most interesting aspects
00:15:25
of of compliment where when you have a t
00:15:28
Target cell and it's maybe recognized as
00:15:30
being foreign or cancerous what's really
00:15:34
interesting then is these compliment
00:15:36
proteins um can activate in response to
00:15:40
antibodies binding to a foreign antigen
00:15:42
here once these complement an proteins
00:15:44
activate they start to arrange in really
00:15:47
interesting orientation where they form
00:15:50
this thing called a membrane attack
00:15:52
complex or MAAC complex and basically
00:15:55
what this macac complex does is it
00:15:57
sticks a big old hole in the cell
00:15:59
membrane of a foreign cell and by having
00:16:02
a huge hole then in the cell it actually
00:16:04
causes the cell to rush in with water
00:16:07
the cell will swell and then burst or
00:16:09
lice open so basically if a foreign cell
00:16:13
encounters the complement Cascade it can
00:16:15
explode because this macac complex
00:16:18
sticks holes in its membrane and
00:16:20
therefore allows an excessive amount of
00:16:22
water to Rush In And this whole cell
00:16:24
explodes like the Death Star so it's
00:16:27
actually pretty cool how this uh
00:16:29
complement Cascade works in the immune
00:16:31
response now something else that's
00:16:33
interesting too is that there are
00:16:36
chemical mediators of immune function
00:16:39
and these chemical mediators are
00:16:40
basically a series of chemicals that are
00:16:42
released by damaged tissue or activated
00:16:45
immune
00:16:46
cells and um some of these include the
00:16:48
kinin um some of the kinin include
00:16:51
things like Brady kinon or cadin and
00:16:53
what these chemical mediators do is they
00:16:55
act in in different ways like they
00:16:57
promote vasod diil a which can increase
00:17:00
blood flow to a particular tissue and
00:17:02
therefore bring in more immune cells
00:17:05
they can activate inflammation they can
00:17:07
activate the clotting Cascade they can
00:17:09
increase vascular permeability which
00:17:11
does a couple things like dilute it
00:17:13
dilutes out bacteria and toxins in a
00:17:15
tissue but it also helps bring in um
00:17:18
more immune cells to an inflamed or
00:17:20
infected tissue uh these Canin are also
00:17:23
involved with smooth muscle contractions
00:17:25
which help form blood clots and it turns
00:17:27
out that the kin are also associated
00:17:29
with pain so if you have an infection or
00:17:33
inflamed portion of tissue um the pain
00:17:37
that could be associated with that is
00:17:39
typically caused by the release of these
00:17:42
kins now what this is showing is the the
00:17:45
pathway that leads to the production of
00:17:47
Kines and what's odd about this pathway
00:17:50
is that it requires something called
00:17:51
Haan factor and going back to the
00:17:54
clotting Cascade you guys remember that
00:17:56
Haan factor is the common factor
00:17:59
that's necessary for both the extrinsic
00:18:00
and intrinsic Pathways of your clotting
00:18:03
Cascade so what's also interesting then
00:18:05
is that yes this hement Factor once it's
00:18:07
activated does promote coagulation of
00:18:10
blood however it also promotes the
00:18:13
production of kinin like Brady Kinnon
00:18:15
that do things like give you a sense of
00:18:17
pain promote inflammation and also
00:18:20
promote vasodilation which can increase
00:18:22
blood flow to an uh an infected or
00:18:25
inflamed tissue so it turns out that the
00:18:27
compliment Cascade uh which is involved
00:18:30
with both
00:18:31
coagulation as well as the immune system
00:18:34
also promotes pain inflammation invasive
00:18:37
dilation now clotting factors do
00:18:40
function and stop and to stop bleeding
00:18:41
we talked about that however we just
00:18:43
learned in the previous slide that
00:18:44
they're involved with inflammation and
00:18:46
trigging triggering the kinen system as
00:18:48
well so there's an interesting interplay
00:18:51
between all these different systems uh
00:18:53
of clotting factors as well as uh you
00:18:56
know inflammation pain and um you know
00:19:00
coagulation of blood now other chemical
00:19:02
mediators of your immune function
00:19:04
include substances like cocin and
00:19:06
chemokines and these are basic chemicals
00:19:09
that can act as chemotactic factors now
00:19:13
chemotaxis literally means chemical
00:19:16
movement and it's not necessarily the
00:19:18
movement of those chemicals but rather
00:19:20
they're chemicals that can attract the
00:19:22
movement of other immune cells to the
00:19:25
site of inflammation or infection and so
00:19:28
what these chemotactic factors can do
00:19:30
then is enhance and coordinate innate
00:19:33
and specific immune defenses they can
00:19:35
activate complex intercellular
00:19:37
communication networks as well as affect
00:19:40
the functioning of other nearby
00:19:43
cells so that these chemotactic factors
00:19:46
do play an important role in the innate
00:19:48
defense and inflammation in fact when we
00:19:51
talk about inflammation it actually is
00:19:52
part of your innate defense so
00:19:54
inflammation isn't always a bad thing in
00:19:56
fact inflammation is part of a normal
00:19:58
and healthy immune response so there are
00:20:01
three main purposes to the inflammatory
00:20:03
response for one it's important for
00:20:05
inflammation to nutralize and Destroy
00:20:07
invading and harmful agents inflammation
00:20:10
also helps to limit the spread of
00:20:11
harmful agent agents in inflammation
00:20:14
also sets up the tissue to be repaired
00:20:17
so these are the three important aspects
00:20:19
of inflammation but we do know that an
00:20:21
excessive amount of inflammation can
00:20:24
lead to uh tissue damage so uh it turns
00:20:28
out that inflammation occurs with any
00:20:30
type of cell injury whether it occurs
00:20:32
exogenously or endogenously an exogenous
00:20:35
type of cell injury would be like if you
00:20:36
get a cut and that that directly injures
00:20:39
injures the tissue otherwise an
00:20:41
endogenous type of cell injury would be
00:20:42
like if cells um you know kill
00:20:45
themselves somehow you know that can
00:20:47
actually lead to certain types of
00:20:49
inflammatory responses and really any
00:20:51
condition that that ends with itis ref
00:20:54
refers to inflammation so if we talk
00:20:56
about vasculitis that refers to to
00:20:58
inflammation of the vasculature or
00:21:00
appendicitis obviously would be
00:21:02
inflammation of the appendix so
00:21:04
inflammation is associated with
00:21:06
infection but not always you know uh
00:21:08
sometimes you can just get inflammation
00:21:09
from tissue damage but not necessarily
00:21:12
due to infection but infections can
00:21:15
cause inflammation and we'll we'll
00:21:17
actually talk about um how those are
00:21:18
stimulated coming up
00:21:20
soon now there are five cardinal signs
00:21:23
of inflammation which include redness
00:21:25
swelling heat pain and and loss of
00:21:28
function now the redness we call Emma
00:21:32
ethema is just sort of a redness of skin
00:21:33
or tissue that's one of the signs of
00:21:36
inflammation um what we see that that
00:21:38
it's also associated with inflammation
00:21:39
would be swelling or just sort of um
00:21:41
where the tissue gets sort of in uh
00:21:43
inflamed or swells with with more fluid
00:21:46
uh it turns out you guys that uh when
00:21:49
there's increase in blood flow to a
00:21:50
particular area you see that inflamed
00:21:53
tissue gets hotter because there's more
00:21:55
blood flow there and due to the release
00:21:57
of kinin you see pain due to tissue
00:21:59
damage however though these do play
00:22:02
important roles in those three
00:22:04
aformentioned functions of inflammation
00:22:07
so helping to dilute out different
00:22:10
factors helping to dilute out bacteria
00:22:13
and also promoting um healing of tissue
00:22:16
but if these occur in excess it turns
00:22:18
out that inflammation can lead to loss
00:22:20
of function or basically tissue damage
00:22:23
so you know excessive inflammation is
00:22:24
not a good thing and this is why you
00:22:27
know if a lot of inflammation in a
00:22:29
particular part of your body it may be
00:22:30
important to take some sort of
00:22:32
anti-inflammatory drug now there's two
00:22:34
types of inflammation we differentiate
00:22:36
acute versus chronic and you all
00:22:38
remember going back to last week we
00:22:39
talked about how um acute symptoms or
00:22:43
signs are short in duration but often
00:22:46
have uh really dramatic initial effects
00:22:51
uh we Define acute inflammation is
00:22:53
lasting less than two weeks and it often
00:22:55
involves a discrete set of in events
00:22:57
events like getting cut and then being
00:22:59
acutely inflamed due to that cut or
00:23:03
burn however chronic inflammation
00:23:05
differs from acute inflammation because
00:23:07
it's more diffuse it's kind of more
00:23:08
widespread throughout your body extends
00:23:10
over longer periods of time right more
00:23:12
than two weeks it can result in Scar
00:23:14
Tissue formation or deformity of that
00:23:16
tissue it can also lead to granuloma
00:23:18
formation which is basically kind of
00:23:20
like a hardness of the tissue so you get
00:23:23
a little bit of loss of function of
00:23:24
there as well so in in many cases
00:23:27
chronic inflammation
00:23:28
can be um you know more dramatic or at
00:23:32
least damaging to tissues versus acute
00:23:35
inflammation now there are three major
00:23:37
events that occur uh with the initial
00:23:40
inflammatory response for one we see an
00:23:43
increase in vascular permeability due to
00:23:46
the fact that mass cells uh release
00:23:49
vasoactive chemicals uh you find these
00:23:51
mass cells in tissue and they basically
00:23:54
just kind of monitor um whether there
00:23:56
are uh you know am uh infectious
00:24:00
microorganisms nearby or if there's any
00:24:02
tissue damage if if either occurs
00:24:05
they'll release vasoactive chemicals
00:24:06
like histamine prostaglandins and lucrin
00:24:09
which increase vascular permeability
00:24:12
what this means is that blood vessels
00:24:13
become more permeable or more leaky so
00:24:16
that some of the components in blood
00:24:17
like water or compliment proteins can
00:24:20
start to leak out in the tissue causing
00:24:23
things like inflammation or
00:24:26
swelling as well as uh bringing
00:24:28
complement proteins that can Aid in the
00:24:31
process of the immune response now uh
00:24:33
another event that occurs during
00:24:35
inflammation is the immigration of Lucy
00:24:38
what we find then is that due to the
00:24:40
release of vasoactive chemicals uh this
00:24:43
can attract Lucy through chemotaxis so
00:24:46
that white blood cells in the
00:24:48
bloodstream can start to marginate or
00:24:51
basically move through the blood vessel
00:24:53
wall from blood into the tissue it turns
00:24:56
out these actually will move through a
00:24:58
process called diapedesis where they
00:24:59
kind of squeeze between cells and this
00:25:01
is attracted through chemotaxis where
00:25:04
these glucosides lucites can kind of
00:25:06
sniff out or smell uh these chemical
00:25:10
markers of inflammation and they're
00:25:12
attracted those markers therefore can
00:25:14
leave blood and enter that inflamed
00:25:16
tissue now the third event in
00:25:18
inflammation is fagocitosis where we
00:25:20
have neutrophils and macrophases
00:25:22
remember this is part of your um your
00:25:25
innate immune response these produce PR
00:25:27
proteolytic enzymes and oxid oxidizing
00:25:30
agents that help to break down the
00:25:33
phagocytose or digested material and
00:25:36
therefore start to remove any foreign
00:25:39
microorganisms or dead tissue um away
00:25:42
from a local
00:25:43
area now these three events of
00:25:45
inflammation can see here so uh what
00:25:47
happens you guys with with inflammation
00:25:49
you get some sort of tissue injury and
00:25:51
we talked about that with tissue injury
00:25:53
that leads to the the release of
00:25:55
vasoactive chemicals that can lead to
00:25:57
things like vasod dilation uh vasod
00:26:00
dilation will increase blood flow to
00:26:01
that tissue which allows for more white
00:26:03
blood cells to enter that inflamed
00:26:05
tissue and therefore participate in the
00:26:08
fosic immune response otherwise injury
00:26:11
can also lead to the release of
00:26:12
chemokines that can also promote
00:26:14
phagocytosis as well as uh nutrifil and
00:26:17
macro macras is leaving or marginating
00:26:20
from the from the bloodstream and
00:26:22
entering uh that infected tissue to also
00:26:25
participate in phagocytosis so you can
00:26:28
see here then that there are multiple
00:26:31
Pathways that result from injury that
00:26:33
all lead to phagocytosis or basically uh
00:26:37
engulfing of that debris or or
00:26:39
microorganisms that can that can Aid or
00:26:41
participate in the immune response and
00:26:44
you might wonder you know well why do
00:26:45
you have three different Pathways that
00:26:47
do the same thing well you know we know
00:26:49
that immune system or
00:26:51
fyos is such an important thing that
00:26:54
you'd want some redundancy here you want
00:26:56
some backup plans where let's say if one
00:26:58
fails at least you have other mechanisms
00:27:00
that can promote the same
00:27:03
process now remember this show the we
00:27:06
have the five cardinal signs of
00:27:07
inflammation which include pain heat
00:27:09
redness and swelling and what this slide
00:27:12
is showing are the different factors
00:27:13
that lead to each of those uh cardinal
00:27:16
signs and actually one of the signs
00:27:17
that's missing up here because there's
00:27:18
only four here is the loss of function
00:27:21
so if you get too much pain heat redness
00:27:23
and swelling that can lead to loss of
00:27:25
function but uh the pain the heat the
00:27:28
renis and swelling are important aspects
00:27:31
of the inflammatory immune response so
00:27:34
what happens then is that with tissue
00:27:36
damage we we get the release of
00:27:37
vasoactive and chemotactic factors and
00:27:40
these do a variety of things for one we
00:27:43
know that vasoactive chemicals and
00:27:45
chemotactic factors can lead to the
00:27:47
production of pain um through the kinan
00:27:50
pathway so that you you know you can get
00:27:53
some pain um due to the release of these
00:27:55
chemicals it turns out that Vaso active
00:27:57
chemicals can also promotee vasodilation
00:28:00
and this vasod dilation can increase
00:28:02
blood flow which actually will cause
00:28:05
redness heat and too much blood flow
00:28:08
also can lead to some pain due to
00:28:11
swelling uh in that tissue um these
00:28:14
chemotactic and vasoactive factors can
00:28:16
also increase the permeability of your
00:28:18
of your blood vessels which cause
00:28:20
swelling in a local area and that
00:28:22
swelling uh is involved in helping to
00:28:24
dilute out any toxins dilute out the
00:28:27
bacteria and also help bring in some of
00:28:30
the nutrients and complement proteins
00:28:33
that Aid in the process of the immune
00:28:36
response here and last but not least you
00:28:38
guys that the vasoactive and Cho
00:28:40
chemotactic factors also promote the
00:28:44
immigration of neutrophils from your
00:28:45
bloodstream into that tissue which also
00:28:49
release a series of factors that promote
00:28:51
swelling now too much pain heat and
00:28:53
swelling and redness uh can lead to loss
00:28:56
of function which um can damage tissue
00:28:59
so again you know inflammation is part
00:29:01
an is an important part of your immune
00:29:03
response however too much inflammation
00:29:06
um can lead to damage of your body's
00:29:11
tissues so the fluid that is actually
00:29:14
going to be um coming from the increased
00:29:17
vascular permeability we call
00:29:19
inflammatory exate so the inflammatory
00:29:22
exit dates are due to the transport of
00:29:24
Lucy and antibodies um so this basically
00:29:28
allows for these substances to come from
00:29:30
blood into the tissue um it's also
00:29:32
involved with diluting toxins and
00:29:34
irrigating substances as well as
00:29:36
transportation of nutrients into the
00:29:38
inflamed tissue for its repair so
00:29:42
exitation inflammatory exate is
00:29:44
basically just the fluid that leaks from
00:29:46
those in those uh permeable vessels
00:29:49
remember the it's the chemotactic and
00:29:51
sakin that really that increase the uh
00:29:53
permeability of blood vessels so what is
00:29:56
what is uh immigration and margination
00:29:59
look like well it turns out that once
00:30:01
these satchin are released by activated
00:30:06
macrophases um they're going to travel
00:30:07
on over to the blood vessel wall here
00:30:11
and once they travel to the blood vessel
00:30:13
wall uh they can activate a series of
00:30:16
receptors that then allow for lucco
00:30:19
sites then to roll across the blood
00:30:22
vessel wall stick to that activated
00:30:25
receptor with the chemokine
00:30:27
once this blood cell cell is stuck to
00:30:29
the blood vessel wall it can start to
00:30:32
squeeze its way through or marginate
00:30:34
through in between two cells and then
00:30:38
enter the infected or inflamed tissue um
00:30:41
once in the infected or inflamed tissue
00:30:43
you know it'll attach to the
00:30:44
extracellular Matrix within that tissue
00:30:46
and then allow basically walk around the
00:30:49
tissue and and find any microorganisms
00:30:52
or um dead cells to
00:30:56
remove now now the process of
00:30:58
Phagocytosis which we talked about was
00:31:00
mediated by things like macroasia and
00:31:03
nutrifil is kind of an interesting and
00:31:06
uh can be a complex process but what
00:31:09
happens is let's say if the immune cell
00:31:12
here uh phagocytosis a microb well what
00:31:16
that what happens then is it puts it
00:31:18
into what we call a
00:31:19
fome which is basically just a vesicle
00:31:22
that results from phagocytosis that
00:31:24
contains your microb within it and then
00:31:27
what happens is the immune cell like a
00:31:29
neutrophil or macras will fuse lomes
00:31:33
with this fome to form what we call a
00:31:35
fago liome now remember lomes are full
00:31:38
of lots of different enzymes and acid
00:31:41
that can act to basically uh break down
00:31:44
this foreign microbe here and it can do
00:31:47
this through a process of like
00:31:49
antioxidants or enzymes and even acid
00:31:52
that basically break down the chemical
00:31:54
structure of the uh basically the microb
00:31:58
inside of this Falone once the microb is
00:32:00
broken down then you know the cell can
00:32:02
recycle those
00:32:04
components and that's how these microbes
00:32:07
are removed from your
00:32:08
body now there are some systemic
00:32:11
manifestations of inflammation we know
00:32:14
that the local inflamm signs of symptoms
00:32:17
of inflammation include those five
00:32:19
cardinal signs we talked about so the
00:32:21
redness heat the pain the swelling and
00:32:23
the loss of function which are
00:32:25
associated with both acute and chronic
00:32:27
inflammation however local inflammation
00:32:30
can lead to systemic involvement because
00:32:33
some of the inflammatory molecules that
00:32:35
are released B inflamed tissue can make
00:32:38
it into your bloodstream uh once they go
00:32:40
systemic these inflammatory molecules
00:32:42
can do things like induce Fever by
00:32:45
basically resetting your hypothalamus to
00:32:47
run your body temperature a little
00:32:49
higher than normal uh can also uh
00:32:52
increase the production of
00:32:54
neutrophils um and cause you to feel
00:32:57
feel more lethargic and it can also
00:32:59
increase muscle catabolism so remember
00:33:01
catabolism means to breakdown so your
00:33:03
body can start to use uh protein and
00:33:06
muscle for
00:33:08
energy now one of the markers of acute
00:33:12
uh inflammation is called C reactive
00:33:14
protein and so C reactive protein is one
00:33:16
of those blood markers for acute
00:33:20
inflammation and we can also measure how
00:33:23
much inflammation someone has in their
00:33:24
body in a laboratory setting by
00:33:26
measuring their arthrite sedimentation
00:33:28
rate or ESR and if their ESR um is
00:33:32
higher this will increase with
00:33:36
inflammation now the specific immune
00:33:39
system uh is remember part of your
00:33:42
immune system that can respond to a
00:33:44
specific antigen now although when we
00:33:47
just talked about the inflammatory
00:33:49
response that was part of your innate uh
00:33:52
immune response the specific adaptive
00:33:54
immune response could be activated as
00:33:56
well as well if those microbes hung
00:33:59
around the tissue long enough to be
00:34:01
recognized by a B cell or a t- cell so
00:34:04
these B cells and te- cells which are
00:34:06
part of your specific adaptive immunity
00:34:08
recognize foreign Invaders and they act
00:34:10
to destroy those foreign Invaders what's
00:34:13
also interesting too is they can retain
00:34:14
a memory of that encounter that way if
00:34:17
you're subsequently exposed to those
00:34:19
foreign Invaders um this going to is
00:34:22
going to allow for a more effective and
00:34:24
quick uh secondary immune response the
00:34:26
next time you're exposed to that
00:34:28
microorganism so the main cell types
00:34:30
that are involved with a specific
00:34:31
adaptive immune response are your B
00:34:33
cells and t- cells uh B cells are
00:34:35
involved with humoral immunity the
00:34:37
reason why we call it humoral immunity
00:34:38
is that the humors of your body or body
00:34:41
fluids and B cells release antibodies
00:34:44
into your body fluids to basically find
00:34:47
and attach to foreign microbes or
00:34:50
antigens now te- cells we call cell
00:34:53
mediated immunity because the te- cells
00:34:56
are involved involved with specifically
00:34:59
targeting um foreign cells now one of
00:35:02
the challenges that B cells and T cells
00:35:05
must undergo is differentiating self
00:35:09
from non-self you know how do B cells
00:35:11
and T cells recognize that a that a cell
00:35:14
belongs in your body so we call it a
00:35:16
self cell or how does it recognize that
00:35:18
a cell is foreign or
00:35:21
non-self now it does this through what
00:35:23
we call the major histo compatibility
00:35:25
complex um also called the human Lucy
00:35:28
antigen or
00:35:30
HLA each individual person has their own
00:35:34
HLA markers that Mark their own body's
00:35:37
cells as self it turns out that your
00:35:40
your individual and unique HLA markers
00:35:44
are dependent on your genotype and last
00:35:47
week we talked about how
00:35:49
[Music]
00:35:51
genotype you know inheritance patterns
00:35:54
that kind of stuff so everyone on the
00:35:56
planet it unless they identical twins
00:35:58
has their own um unique HLA which
00:36:02
basically marks their body cells as self
00:36:06
now no one has the same image see unless
00:36:08
they're identical twins and this is
00:36:10
because of uh genetic recombination
00:36:12
which occurs during meiosis we get sort
00:36:15
of shuffling of genes and so even for
00:36:17
close relatives like brothers and
00:36:19
sisters which you know presumably have
00:36:21
the same genes the thing is though is
00:36:24
that they inherit different combinations
00:36:26
of the types of those genes or forms of
00:36:28
those genes from their parents due to
00:36:30
shuffling of genes during meiosis so
00:36:33
even if you have a brother and sister um
00:36:36
that you inherit your DNA from the same
00:36:37
parents you have different forms of
00:36:40
those genes from each parent which means
00:36:42
you're even though you're interrelated
00:36:44
you're also slightly different now MHC
00:36:48
comes from basically your genome so your
00:36:52
chromosomes and there's different
00:36:53
classes of MHC we have class one two and
00:36:55
three class 1 MHC are basically
00:36:59
receptors for antigen presentation for
00:37:02
nucleated cells Class 2 MHC are
00:37:05
receptors for antigen presentation found
00:37:07
on macras and B cells and class 3 MHC
00:37:12
are used for complement components and
00:37:15
other immune
00:37:16
cells now uh nucleated cells all Express
00:37:20
MHC class one receptors on their cell
00:37:23
surface and this is important because
00:37:25
cytotoxic cells can recognize these
00:37:27
antigens um on mhcu class one cells and
00:37:31
then recognize whether those cells are
00:37:33
foreign or they belong in your cell
00:37:36
other specialized cells like dendritic
00:37:38
cells macrophases B cells Express MHC
00:37:41
Class 2 proteins and these uh play a
00:37:44
role with the t- helper cells in
00:37:46
recognizing antigens as being foreign or
00:37:50
belonging to
00:37:51
yourself now it turns out that nucleated
00:37:54
cells are continuously producing mhc1
00:37:57
proteins by their endoplasmic reticulum
00:38:00
and it turns out that as these are
00:38:02
producing MHC class one proteins these
00:38:05
actually will fuse with other protein
00:38:07
fragments in the cytoplasm so what's
00:38:09
kind of odd is that these MHC class one
00:38:12
proteins are used as a marker to kind of
00:38:16
identify what's going on inside of cells
00:38:18
because they're constantly binding with
00:38:20
little fragments within those cells now
00:38:22
what happens is these MHC class 1
00:38:24
proteins and those peptide frag
00:38:26
fragments eventually get expressed on
00:38:29
the cell surface and these are expected
00:38:31
by T I'm sorry these are inspected by
00:38:34
the T
00:38:36
cells around the humor or fluids of your
00:38:40
body now what's interesting here then is
00:38:42
that these te cells then by recognizing
00:38:45
mhc1 complexes uh with the peptide
00:38:49
fragments can really kind of see what's
00:38:51
going on inside of your body cells uh in
00:38:54
real time so so the reason why this is
00:38:57
important is that this is one of the
00:38:59
ways that cytotoxic tea cells can
00:39:01
recognize whether a cell is virally
00:39:03
infected or not you know because we know
00:39:06
that viruses must get inside of a cell
00:39:09
in order to divide so how do we know
00:39:11
whether our immune cells know if a a
00:39:15
cell contains a virus or doesn't contain
00:39:17
a virus well once that virus enters a
00:39:20
cell you know it takes its genome and
00:39:23
starts to use the host cell Machinery to
00:39:25
make viral proteins now it turns out
00:39:28
those viral proteins will fuse with a
00:39:30
class one MHC receptor which then gets
00:39:33
expressed on the cell surface so
00:39:35
basically it's a way for the cell to
00:39:37
show hey it has viral proteins inside of
00:39:40
it and this is one of the ways that the
00:39:42
cytotoxic tea cells can recognize
00:39:45
whether there are viral proteins being
00:39:47
expressed in a given cell of your body
00:39:49
if this is the case if a cot toxic te-
00:39:51
cell recognizes that a cell is virally
00:39:54
infected this cot toxic t cell then will
00:39:57
initiate um the process of
00:40:01
uh basically coordinated cell death
00:40:04
which is apotosis so cytotoxic te cells
00:40:06
will then kill a virally infected cell
00:40:09
which is kind of interesting now this
00:40:11
differs from the class 2 MHC proteins
00:40:14
because MH Class 2 MHC proteins present
00:40:17
antigens that are obtained from the
00:40:19
extracellular sources remember this
00:40:22
differs from class one MHC because class
00:40:24
one actually obtains proteins from
00:40:26
within cells class two obtains proteins
00:40:29
that you find outside of cells so that
00:40:32
these ones are associated with the the
00:40:34
phagocytic cells like neutrophils and
00:40:38
macras now it turns out these
00:40:40
extracellular antigens or proteins must
00:40:43
first be ingested by antigen presenting
00:40:45
cells like macroasia and nutrifil
00:40:48
through a process of
00:40:49
Phagocytosis so that these
00:40:52
um macras and nutrifil will fake oyos
00:40:57
any kind of extracellular debris it'll
00:41:00
basically fuse that with lome and chop
00:41:02
this up into little bits it can take
00:41:04
those peptide fragments fuse it with a
00:41:06
Class 2 MHC receptor and then Express
00:41:09
that on its cell surface this is one of
00:41:11
the ways that these cells can present
00:41:13
antigens to other immune cells to get
00:41:16
the rest of the immune cell excited um
00:41:18
in some ways it's kind of basically kind
00:41:20
of showing what it caught so once it
00:41:23
catches this foreign protein it'll chop
00:41:25
it up put it on mhc2 MHC Class 2
00:41:28
receptor exess Express that on its cell
00:41:31
surface and then say hey helper T cell
00:41:33
look what I found and then the helper T
00:41:35
cell will will recognize this as being
00:41:37
foreign and then that will help initiate
00:41:40
an immune response because if you
00:41:41
remember helper T cells release cokin
00:41:44
which then can then can activate the
00:41:46
cytotoxic te- cells and your B
00:41:50
cells so um uh it turns out that cell
00:41:55
mediated immunity involves your te-
00:41:57
cells and uh these te- cells have their
00:42:00
own specific receptors and it's used to
00:42:03
recognize foreign antigens that you find
00:42:05
on antigen presenting cells now these
00:42:08
te- cells are specific so they only
00:42:10
recognize one specific type of antigen
00:42:14
but what this means then is that you
00:42:15
have lots of different types of te-
00:42:17
cells that respond to their own specific
00:42:20
type of antigen and what this allows for
00:42:23
then is your immune system can recognize
00:42:25
potentially Millions or billions of
00:42:27
different types of antigens uh which may
00:42:30
be foreign to your body and we know that
00:42:32
there's two types of te- cells we have
00:42:33
the helper and cytotoxic te- cells and
00:42:35
the function of these helper te- cells
00:42:37
which are CD4 positive is to release
00:42:40
cines that activate other immune cells
00:42:42
and the cytotoxic te- cells are the ones
00:42:45
that directly participate in the immune
00:42:47
response by basically you know directly
00:42:50
targeting a foreign cell so the T cells
00:42:53
we talked about with CD4 positive you
00:42:54
know these are involved with with the
00:42:56
MHC Class 2 pathway they're CD4 positive
00:42:59
so that they're going to be possibly
00:43:01
infected by the HIV virus and um these
00:43:05
recognize one specific type of antigen
00:43:08
and this differs from cytotoxic te-
00:43:10
cells because these are cd8 positive um
00:43:12
these are involved with the MHC class
00:43:14
one pathway um now HIV does not infect
00:43:18
cd8 positive cells but HIV still has an
00:43:22
a dramatic effect on your immune system
00:43:24
because you're removing the CD4 positive
00:43:28
uh set helper T cells which are
00:43:30
necessary to get the rest of your immune
00:43:31
system
00:43:33
excited now uh once these um cd8
00:43:38
proteins um are used with this mhc1
00:43:42
pathway it can trigger a response that
00:43:45
causes cytotoxic tea cells um to
00:43:49
activate also other cells like t- helper
00:43:52
cells and so uh it turns out that it's
00:43:55
not enough that you only have cot toxic
00:43:58
te- cells recognizing something foreign
00:44:00
it also requires unique co- stimulation
00:44:03
by Inner lucans and cocin released by
00:44:06
the helper te- cells so it's almost as
00:44:08
though these cytotoxic te- cells need
00:44:10
other immune cells to kind of
00:44:12
corroborate its story that it's
00:44:14
recognizing a foreign
00:44:17
microorganism now the cytotoxic te-
00:44:19
cells um once activated can proliferate
00:44:22
into memory cells and affector cells the
00:44:25
memory cells will remain dormant and
00:44:27
store a memory of that infection whereas
00:44:29
the affector cells are the ones that are
00:44:31
the will participate directly in the
00:44:34
immune response by targeting that
00:44:36
foreign microorganism and the way that
00:44:39
these cot toxic tea cells remove foreign
00:44:41
microorganisms these affector cells do
00:44:43
is that they produce something called
00:44:44
perforins and these perforins are
00:44:46
manufactured by cytotoxic tea cells and
00:44:49
they basically um punch holes instead of
00:44:52
foreign cells and then inject granzymes
00:44:55
into the Target cell which degrades its
00:44:57
DNA and allows for apotosis or basically
00:45:00
cell death to
00:45:02
occur so I like to think about these cot
00:45:04
toxic tea cells as being like the grim
00:45:06
reapers of your immune system because
00:45:08
once they touch a foreign
00:45:10
microorganism or uh you know like a
00:45:13
cancer cell it can actually cause that
00:45:15
cell to kill itself through a process of
00:45:17
apotosis which is actually pretty cool
00:45:20
now the B cells are involved with your
00:45:22
humoral immunity and there's two major
00:45:24
types of B cells we have memory cells
00:45:26
and plasma cells so once B cells are
00:45:28
activated you know some of these cells
00:45:30
will go dormant and store a memory of
00:45:31
that infection that way your immune
00:45:33
system is ready to uh remember that
00:45:36
infection in the future otherwise the
00:45:38
plasma cells are the activated B cells
00:45:41
that are basically like big old antibody
00:45:44
factories and um once these cells are
00:45:47
activated um they divide into clones so
00:45:49
you can get a lot of different plasma
00:45:51
cells that can really rapidly produce a
00:45:54
lot of antibodies
00:45:56
now these antibodies are basically short
00:45:59
I'm sorry the plasma cells are
00:46:00
short-lived antibod producing factories
00:46:03
and all plasma cells secrete antibodies
00:46:06
with identical structure now what these
00:46:08
antibodies do is they're little
00:46:10
molecular probes that bind specifically
00:46:13
to a foreign antigen once that antibody
00:46:17
binds to a foreign antigen um it
00:46:19
initiates immune response that we'll
00:46:21
talk about here in a little bit um but
00:46:23
once the the infection dies off those an
00:46:26
and the antigens are cleared
00:46:28
um there are some memory cells that will
00:46:31
live on to recognize antigens if you're
00:46:34
reexposed to that uh you know
00:46:37
microorganism so activation of B cells
00:46:40
does require t-h helper cells as well so
00:46:42
that t- helper cells release sakin that
00:46:45
also activate B cells and this um
00:46:48
requires some cellto cell contact
00:46:50
between B and T cells now the cellto
00:46:53
cell binding of B and T helper cell
00:46:55
cells promotes clonal expansion which
00:46:58
basically means that you can produce
00:46:59
more clones of these B cells so they can
00:47:02
divide rapidly and um this can
00:47:05
proliferate and begin antibody synthesis
00:47:08
so um what happens you guys is these
00:47:10
antibodies are also called
00:47:12
immunoglobulins and they're basically
00:47:13
just protein chains that are um joined
00:47:17
by two identical heavy protein chains
00:47:20
that have what are we called disulfide
00:47:21
bonds these there's five main classes of
00:47:24
antibodies
00:47:26
we have IG IGM IG d and e um IGG is the
00:47:33
most common it's also the smallest of
00:47:35
your antibodies so it can really easily
00:47:38
Escape your bloodstream uh because it's
00:47:40
so small it's it can really easily slip
00:47:42
through the spaces between some of the
00:47:45
cells that line your blood vessels and
00:47:47
these circulate as single molecules but
00:47:49
they can enter uh a lot of the
00:47:51
interstitial fluids of your body now IGM
00:47:54
is the largest and think about this is
00:47:56
like the monster so IGM is the monster
00:47:59
antibody it consists of five antibody
00:48:02
molecules that are joined together to
00:48:03
form a pentamer sort of five together
00:48:06
it's mostly found in your vascular pool
00:48:08
because it's so big it can't cross the
00:48:09
capillary wall it's the first to be
00:48:11
produced upon exposure to antigens and
00:48:14
it's the major antibody found on B cell
00:48:16
surfaces and it's one of its main
00:48:18
functions is to activate compliment we
00:48:21
learned earlier that once you activate
00:48:23
compliment that does a variety of things
00:48:25
like promote the coagulation Cascade um
00:48:29
attract other immune cells to that side
00:48:31
of infection but can also activate the
00:48:34
Mac attack complex which can punch holes
00:48:36
into foreign cells but it's the IGM here
00:48:39
once it binds to a foreign cell it can
00:48:41
actually activate complement that can
00:48:43
punch a hole in that foreign
00:48:45
cell IG is a dimer so it's not really
00:48:48
small but it's going to be larger than
00:48:51
IGG it's also produced by plasma cells
00:48:54
that you find in tissue or you know like
00:48:56
skin and mucous membranes um because
00:48:59
it's small um you can find IGA in Sal in
00:49:04
secretions like saliva tears uh in
00:49:07
mucosal secretions like trob bronchial
00:49:10
secretions as well as colostrum and
00:49:12
breast milk now uh you might wonder why
00:49:15
would you find an antibod in certain
00:49:17
secretion like saliva tears uh trob
00:49:19
bronchial secretions and breast milk
00:49:22
well this antibody can confer immunity
00:49:24
in that regard so you know saliva has
00:49:28
antimicrobial aspects because it has
00:49:30
antibodies in it tears have
00:49:32
antimicrobial aspects because they have
00:49:34
antibodies in it and even breast milk
00:49:36
has some
00:49:37
antimicrobial aspects because it
00:49:40
contains its mother's uh antibodies so
00:49:43
that a newborn gets some immunity due to
00:49:47
uh you know the absorption of um these
00:49:49
antibodies from the mother so it's
00:49:51
pretty cool now igd is found in more
00:49:54
small amounts in your blood it's located
00:49:57
primarily on B cell
00:49:59
membranes and it's thought to be the
00:50:01
antigen receptor that acts to stimulate
00:50:03
B cells to multiply differentiate or
00:50:06
secrete other specific amog globulins so
00:50:09
igd seems to have more of like a
00:50:12
regulatory aspect in the immune response
00:50:15
now this differs from IG because IG
00:50:18
circulates as a single molecule it's um
00:50:21
can be bound to basophils and mass cells
00:50:23
it's found in more Trace Amounts than
00:50:25
serum
00:50:26
but it's often involved with immunity
00:50:28
against helic parasites remember helmets
00:50:31
are the worm type parasites so IG is
00:50:34
associated with parasitic infections
00:50:36
hence the basophil and mass cell
00:50:39
Association and therefore it's also
00:50:41
associated with allergic reactions and
00:50:44
this is believed to be involved as a
00:50:46
signaling molecule during the parasitic
00:50:49
and Allergy
00:50:52
responses now what's interesting though
00:50:54
is that although these B cells are
00:50:57
antibody factories they can actually
00:51:00
produce different types of antibodies so
00:51:02
antibodies like IGM and igd can be
00:51:05
switched interchangeably uh between the
00:51:08
different types of antibodies so it's
00:51:09
pretty cool so remember IGM is is the
00:51:12
monster molecule so it's the large one
00:51:14
and IGM and igd can be switched to other
00:51:16
smaller ones like g e and a by what we
00:51:19
call class switching so class switching
00:51:22
is influenced by the presence of certain
00:51:23
cyto kindes so you're immune cells can
00:51:26
alter what types of antibodies you have
00:51:29
present in your body and that can
00:51:31
promote a more effective immune response
00:51:34
and so class sing can be used to
00:51:35
identify acute versus chronic infections
00:51:38
so with acute infections you're going to
00:51:40
find a lot of more uh IGM type of
00:51:42
antibodies because those are the first
00:51:44
that are produced however if it's if
00:51:46
it's a chronic infection you're going to
00:51:48
be you're going to find a lot more of
00:51:49
the smaller type of antibodies because
00:51:51
they've had time to class switch from
00:51:53
the larger ones like IG and
00:51:56
igd now you might wonder well what are
00:51:58
the functions of antibodies you know we
00:52:00
we called them molecular probes earlier
00:52:04
and if these are molecular probes what
00:52:05
are they doing well when these
00:52:07
antibodies stick to a foreign cell they
00:52:09
do a couple things for one they can
00:52:12
precipitate uh cells or substances from
00:52:15
your body so they can remove substances
00:52:17
from Body
00:52:19
Solutions these antibodies can also
00:52:21
cause cells to uate or Clump together
00:52:24
and by allowing these foreign cells to
00:52:25
Clump together they're actually easier
00:52:27
to remove in that regard now antibodies
00:52:30
can also neutralize toxins because if a
00:52:32
toxin's bound up to an antibody it can't
00:52:34
exert a Toxic effect in a tissue and
00:52:37
antibodies are also involved with
00:52:39
opsonization because they can flag a
00:52:42
foreign cell for phagocytosis so certain
00:52:45
phagocytes like macrophases and
00:52:47
neutrophils can specifically remove
00:52:50
foreign cells that have antibodies stuck
00:52:52
to them uh but it turns out that
00:52:54
antibodies can can also activate
00:52:56
compliment and we know that compliments
00:52:57
involve with chemot taxis or attracting
00:53:00
other immune cells uh inflammation as
00:53:02
well as the membrane attack complex or
00:53:05
Mac attack complex which basically
00:53:06
punches holes in foreign
00:53:09
cells now for the last part of this
00:53:11
chapter what we're going to wrap up with
00:53:13
is differentiating passive versus active
00:53:16
immunity and before we get to passive
00:53:18
versus active immunity we should Define
00:53:20
just generally what is immunity well we
00:53:23
know kind of anecdotally that immunity
00:53:25
is as a state of resistance against
00:53:28
infection like if you have an immune
00:53:29
response then you're resisting infection
00:53:31
in your body and it's provided primarily
00:53:34
by adequate levels of antibodies and
00:53:37
other cells now we talk about the
00:53:39
concentration of antibodies in your
00:53:41
serum as being an antibody Tighter and
00:53:43
if you have a blood test for antibody
00:53:45
tighter you're basically looking for
00:53:47
certain antibody
00:53:48
concentrations and types of antibodies
00:53:51
which can suggest um different types of
00:53:54
immunity that's going on on now what's
00:53:57
interesting is that antibodies can
00:53:59
achieve both active and passive immunity
00:54:02
active immunity is actually I'm sorry
00:54:05
we're going to start with passive
00:54:06
immunity so passive immunity is the
00:54:08
transfer of preformed antibodies against
00:54:12
a specific antigen to an individual so
00:54:16
an example of passive immunity could be
00:54:18
like how an infant can receive
00:54:21
pre-formed antibodies from a mother
00:54:23
through breast milk
00:54:25
and we would call that naturally
00:54:27
acquired passive immunity so because an
00:54:30
infant is naturally getting uh
00:54:32
antibodies through a mother's breast
00:54:34
milk that's a form of naturally acquired
00:54:36
passive immunity there's also other
00:54:39
forms of naturally acquired passive
00:54:40
immunity like for instance a fetus can
00:54:43
receive antibodies through placental
00:54:45
transfer so some of the mother's
00:54:48
antibodies can make it through the
00:54:49
placenta to Aid in um immunity within a
00:54:54
fetus
00:54:56
now there's also something called
00:54:58
artificially acquired passive immunity
00:55:00
and if it's artificial that means that
00:55:02
this is actually being received through
00:55:03
sort of medical interventions so what's
00:55:06
interesting is that scientists know how
00:55:08
to create certain types of antibodies in
00:55:10
a lab so let's say if you're infected
00:55:12
with a with a known pathogen like a
00:55:14
certain type of virus well if you know
00:55:17
what type of antibody attacks that virus
00:55:20
or pathogen then scientists can make
00:55:22
that antibody in lab and then inject
00:55:25
that specific antibody into someone's
00:55:27
body to confer an artificial form of
00:55:30
passive immunity so you can artificially
00:55:33
inject uh pre-formed antibodies into
00:55:35
somebody to confer this passive immunity
00:55:38
so one of the key points with passive
00:55:40
immunity is that if someone has passive
00:55:42
immunity they're not making the
00:55:44
antibodies thems rather they're
00:55:47
receiving those antibodies from other
00:55:49
means like if it's if it's natural
00:55:51
you're receiving it from a mother
00:55:53
through breast milk or or placental
00:55:56
transfer and if it's artificial you're
00:55:59
receiving them in a in a clinical
00:56:01
setting where you might be injected with
00:56:03
with antibodies uh to help fight an
00:56:07
infection now this is used for B cell
00:56:09
amuno
00:56:11
deficiencies and um antibody injection
00:56:14
May alleviate or suppress the effects of
00:56:17
a particular toxin so when we talk about
00:56:22
um when we talk about antivenoms that
00:56:25
kind of stuff or
00:56:26
antitoxins uh those are often antibodies
00:56:29
against those toxins that we've
00:56:31
harvested um through sort of scientific
00:56:33
means if that makes sense now what one
00:56:36
important note with passive immunity is
00:56:38
that it provides immediate but temporary
00:56:42
Pro protection because if someone's
00:56:44
receiving pre-formed antibodies outside
00:56:46
their body like through Brothers I'm
00:56:48
sorry mother's breast milk or through
00:56:51
clinical injections you're not training
00:56:54
their body to learn how to make those
00:56:56
antibodies on their own they're just
00:56:58
temporarily receiving those antibodies
00:57:00
to alleviate that infection however the
00:57:02
person won't learn how to fight that
00:57:04
infection on their own so that's one one
00:57:06
important note with passive
00:57:09
immunity now there's different types of
00:57:11
passive immunity like you can get uh
00:57:13
mother to fetus transfer right so that
00:57:15
can cross the placenta or mother to
00:57:17
infant transfer we might have IGA in
00:57:19
breast milk otherwise you have cotherapy
00:57:22
where you might have direct injection of
00:57:24
antibodies into um you know from human
00:57:27
or animal directly into a patient to
00:57:29
help fight
00:57:30
infection now this differs from active
00:57:33
immunity because active immunity is
00:57:35
where an individual's own immune system
00:57:38
can produce its own antibodies against
00:57:41
infection now this requires memory B
00:57:44
cells because memory B cells will store
00:57:45
a memory of that infection and upon an
00:57:48
SEC second exposure you'll get a quicker
00:57:51
response so active immunity um would uh
00:57:56
involve things like
00:57:58
immunizations because a
00:58:00
vaccine can stimulate someone's immune
00:58:04
system to develop immune cells against a
00:58:07
particular antigen or you know foreign
00:58:11
protein because vaccines contain foreign
00:58:14
antigens they stimulate um you know uh
00:58:18
basically immune responses but they
00:58:20
don't have pathogenic properties so
00:58:22
vaccines don't cause disease an
00:58:25
individual they don't cause harm to the
00:58:26
host some vaccines contain live or
00:58:29
attenuated live or attenuated agents but
00:58:32
they don't cause disease in the host but
00:58:34
what this does is it it stimulates a
00:58:36
normal immune response in somebody that
00:58:39
way they can produce B cells and te-
00:58:41
cells against an antigen that and they
00:58:44
can produce their own antibodies against
00:58:46
that infection and because this
00:58:47
individual is producing their own
00:58:49
antibodies we call this active immunity
00:58:52
now immunizations or vaccines
00:58:55
are an example of artificially acquired
00:58:58
active immunity because you're
00:59:00
artificially injecting a antigen into
00:59:03
someone's
00:59:05
body um now what this is showing is the
00:59:08
difference between the primary versus
00:59:10
secondary immune response and you can
00:59:12
see that with the primary immune
00:59:14
response let's say if we if we are
00:59:16
exposed to a foreign microorganism it
00:59:19
can take 10 or more days before we start
00:59:22
producing antibodies against that micro
00:59:24
organism remember IGM is the first type
00:59:27
of antibody that's produced and then you
00:59:29
can get class switching to smaller
00:59:30
antibodies like IGG but that takes time
00:59:34
and so it's important to note that if
00:59:36
you're first exposed to a foreign
00:59:38
microorganism it actually takes time to
00:59:40
develop antibodies against that
00:59:42
microorganism because with this specific
00:59:45
adaptive immune response uh it's a
00:59:47
little bit more slow to develop however
00:59:51
once you develop immune cells against a
00:59:54
specific ganogen those immune cells can
00:59:56
differentiate into memory cells and then
00:59:58
go dormant in your body which means the
01:00:01
second time you're exposed to that
01:00:03
antigen the response is much quicker so
01:00:06
you can see that instead of taking 10
01:00:07
days to get antibodies produced it can
01:00:10
take as little as three days or even
01:00:12
less to start to produce antibodies
01:00:14
against that microorganism so the
01:00:16
secondary response is much quicker and
01:00:19
much more dramatic so you get more
01:00:21
antibodies being produced the second
01:00:23
time but let's talk about this with
01:00:26
respect to the um you know whole the
01:00:29
whole idea behind vaccination you know
01:00:31
vaccination simulates the primary
01:00:34
stimulus so if you receive a vaccine
01:00:36
that's like getting a primary immune
01:00:37
response so you get a vaccine and you
01:00:40
know the antigens float on your
01:00:41
bloodstream for some time and then you
01:00:43
then you develop immune cells that can
01:00:45
produce antibodies against those
01:00:47
antigens but let's say that um you know
01:00:50
those memory cells go dormant but what
01:00:52
about if if you on the second St
01:00:54
stimulus what if you were really exposed
01:00:56
to that microorganism that could cause
01:00:58
disease well the the first time you're
01:01:01
exposed to that microorganism is
01:01:03
actually like the secondary stimulus or
01:01:05
response because you've already been
01:01:07
exposed to the antigens of that
01:01:09
microorganism which means even though
01:01:11
it's the first time you're being exposed
01:01:13
to that
01:01:14
microorganism it's almost like you're
01:01:15
being exposed for the second time
01:01:17
because you already have memories
01:01:18
against against the antigens of that
01:01:21
microorganism so you get anti body
01:01:23
production much more more quickly which
01:01:25
means you have a stronger immune
01:01:27
response upon exposure to that
01:01:31
microorganism now one thing that's
01:01:32
important to note is that vaccines don't
01:01:35
always confer absolute immunity you know
01:01:38
just because you you've had a vaccine
01:01:39
against the particular microorganism
01:01:42
like influenza or hepatitis uh doesn't
01:01:45
mean you're totally immune it just means
01:01:47
that if you are expose your secondary
01:01:50
immune response here uh will kick in and
01:01:52
you're going to have a really strong
01:01:54
immune response which means you're more
01:01:55
likely to clear off that infection
01:01:58
before it causes disease