00:01
Hello and welcome.
00:02
This next series of talks are
going to be about the immune system
and how the immune system
can cause pathology,
so immune mediated injury.
00:13
In general,
the immune system is a good guy.
00:17
The immune system is there to
defend us against infection,
it turns out because tumors
generate foreign antigens.
00:24
We also use the immune system
as a surveillance mechanism.
00:28
And it probably protects us from
malignancy up to a point as well.
00:35
How does it do this?
How does the immune
system do its job?
Basically, because it can
distinguish self from non self,
that seems very straightforward
and self evident,
except when you think about it.
00:47
Let's get down to
the molecular level.
00:49
Think about the amino acids,
it's the same amino acids bacteria in us,
it's the same sugars, me and us,
us and them.
00:58
It's the same lipids as an M.
01:00
So how we actually can recognize a
3-dimensional conformation and say,
"That's me, leave me alone."
versus, "Oh, that's not
me, I need to attack that"
is not trivial and it's really kind
of an important overall concept.
01:14
We're going to just kind of glide over the
surface without getting too much in depth.
01:18
But keep that in mind.
01:20
Once the immune system is
triggered, once it says,
"Hey, that's not me."
I need to respond to that.
01:27
It brings to bear a
whole host of pathways
that allow it to respond and
hopefully clear whatever invading army
is coming into the system.
01:38
They're redundant,
they're overlapping,
but the responses are
many and multiple.
01:43
But once I provide for you,
in the next series of
talks, a toolkit,
you'll be able to
predict pretty reliably
what is going to
happen if I elicit
this particular response or
that particular response.
02:00
Their job is to clear, to kill whatever
has invaded and to clear the debris.
02:06
There's a potential however,
for a lot of damage,
so you can have too
exuberant a response.
02:12
You can just have
too many neutrophils,
too many macrophages
making too many mediators
and cause damage in that way.
02:20
You can also have,
as we mentioned,
you can have autoimmunity,
you can have a response to self.
02:27
That happens because we just don't
eliminate those self reactive clones.
02:32
Okay,
next slide of big
picture concepts.
02:36
So the responding cell
recognizes that there
is something wrong,
we'll talk in the next series of talks
about how it knows that something is wrong.
02:46
Those responding cells by
themselves can't do very much.
02:50
A single cell probably
doesn't make much inroads
when it comes to getting
rid of an invader.
02:57
But if I turn it on,
and it proliferates,
now we're talking,
now I've got an army
of like-minded cells
recognizing the same thing
that can work
together and eliminate
whatever is going on,
pathogen or tumor.
03:15
Those responding cells by
themselves, in many cases,
can't do the full job,
they need to recruit in additional cells.
03:23
So we will see in
the next few slides
that if I activate
a T cell population.
03:29
It will make cytokines to recruit
in macrophages and neutrophils,
who can do a lot of
the heavy lifting.
03:35
So I need to have
some something,
some cell that can initially
say, "That's bad",
and then who can proliferate,
make more of itself,
and then pull in a whole
bunch of buddies to do
battle with whatever
the invader is.
03:51
There gonna be a number
of mediators produced.
03:53
So it's not just
killing, it's not just,
you know,
shooting bullets at each other.
03:58
But in fact, there's going to be
various agents, nerve
gases, not nerve gases,
but various things that are
secreted into the environment.
04:06
So those mediators are
going to be produced,
and they will potentially
have good things to do,
but could also be pathogenic.
04:13
And eventually,
hopefully, we, our body,
our immune system is successful,
we remove the stimulus.
04:21
And/or we establish feedback inhibition
to turn the whole system off,
and the sponsor resolves.
04:28
If we don't carefully
regulate those steps,
we just fight and fight
and fight and fight,
which can lead to scarring,
more tissue damage, etc.
04:37
Okay, so those are the big
kind of overarching concepts.
04:41
Let's dive a little bit
deeper at this point.
04:43
So there are two basic flavors
of the immune response.
04:46
And when I talk about immune response,
I'm not just talking T cells and B cells.
04:50
I'm actually talking about
the innate immune response,
which is going to be neutrophils
and macrophages and complement.
04:56
So various components
that are there.
05:00
And having nonspecific immunity,
and we're going to be talking about
adaptive immunity on the right hand side.
05:05
Those are going to be the T cells
the T lymphocytes, the B lymphocytes,
and antibodies produced
by B lymphocytes.
05:12
They work in, in sequence.
05:16
They also cross
talk and collaborate
to be the most effective in
dealing with infection or damage.