>>Dr. Ketchum: So we are going to go ahead
and continue our discussion of the immune
system, and we’ll be discussing innate immunity.
Now before we discuss innate immunity, you
need to understand that there’s actually
two different types of immunity—one of those
being innate immunity, which is also called
nonspecific immunity, and the other is called
acquired or adaptive immunity, which is also
known as specific immunity. But just to give
you a quick overview of both of these, when
you first think about the nonspecific or the
innate immunity, it’s a very rapid response.
This is your first line of defense. And what
this does is it gives your body time for the
specific immunity to kick in. So innate immunity
is always there. It’s present; it’s going
to happen as soon as your body is invaded
by a foreign object, and then the specific
immunity will take over after that. It’s
rapid, and it’s also not selective. So it’s
not targeting specific species of invaders,
for example. It’s not specific. It just
wants to kill foreign invaders, and that’s
the end of it. The innate immunity involves
physical and chemical barriers, and it also
includes cellular defenses. Now once the innate
immunity has occurred, then the next type
of immunity that will occur or kick in is
the acquired immunity. It’s a slow response.
And so because it’s a slow response, it’s
very selective in what it’s killing. It
may kill a specific bacterial cell or a specific
virus, and specific immunity includes two
different types of responses—humoral responses,
which are also called antibody-mediated responses,
and cell-mediated responses, which are also
called cytotoxic lymphocytes. Here’s our
analogy. When you think about an innate response,
the castle is the body. And the first thing
that this innate response wants to do is it
wants to prevent that invader from entering
the body. And once that invader invades the
body, then the innate response will have some
other methods for killing the invaders as
well. These things are all taking place as
the acquired response is just getting started—but
remember it’s slow, so it takes a while
to get the acquired response going.
So neutrophils, the eosinophils, basophils
and monocytes are all cells that are important
in an innate response. The lymphocytes, on
the other hand, are the type of white blood
cell that are important in the acquired response.
You don’t have to memorize the amount of
each of these cells in a microliter or their
diameters or any of that. You need to understand
their anatomical features and their functions.
So these are important columns here, but you
do also have to know their abundance—their
relative abundance. So again, if you remember
“Never Let Monkeys Eat Bananas,” that
tells you the most abundant leukocyte all
the way to the least abundant leukocyte, which
are your “bananas” or your basophils,
so that way you don’t have to memorize the
amount per microliter. The reason this is
important is because if you’re looking at
a slide—let’s say you take a blood smear
on a microscope slide—and, and this is a
healthy person, and you’re going through
and you’re identifying all the various white
blood cells. Well if you’re finding more
basophils than you are neutrophils, then you’re
probably not correctly identifying those cells.
Okay, so here’s a flow chart that I put
together to help organize the innate versus
the adaptive response. So you’re definitely
going to want to use this as your road map.
We’re discussing the innate responses in
this part, in part two.
First let’s start with the physical and
the chemical barriers; you think about these
as being the wall of the castle. So the first
thing I’d like to discuss are the lysozymes.
So you have lysozymes that are in your tears
and other secretions. These are not lysosomes;
lysosomes are different. Lysozymes are antibacterial.
So when you cry, it’s actually a good thing
because you’re killing any kind of bacteria
that’s on your skin. You also have the skin,
then, and the skin is a physical barrier.
The skin also has fatty acids and normal flora
as well that’ll affect the pH and some foreign
invaders cannot survive on the skin just because
of the normal flora on our skin. Then you
have the mucus and the cilia that line the
trachea. The mucus traps any formed particles,
and then the cilia works that debris up the
respiratory tract and into your mouth so that
you can either swallow it or spit it out.
If you swallow it, it goes down into your
stomach. And remember, the stomach has a pH
of two; it’s very acidic. So it’s likely
to kill most invaders, but not all. Now taking
a closer look at the skin, we’re not going
to spend time on the skin. This isn’t anatomy,
but you should realize in this course that
you do have two major skin layers: the epidermis
and the dermis. So pay attention to those
two layers and know where those two layers
are located—which one’s on the outermost
which ones on the innermost.
The dermis, then, the only thing that you
need to know about the dermis are the sebaceous
glands, and I want you to use your textbook
to figure out what’s the function of those
sebaceous glands? Why are they important in
the immune response? Then we have inflammation.
So inflammation is part of the innate immunity
as well. When you think about inflammation,
it’s your body’s response to tissue damage
or microbial invasion. So you’ve sprained
your ankle and your ankle is now inflamed.
You stepped on a nail, and—so now you have
tissue damage and microbial invasion by stepping
on a nail. So the goals of inflammation are
listed here for you. You want to bring phagocytes
to the injured area, because if you can control
those invaders at the area that they’ve
invaded, then they can’t spread throughout
the body. You want to stop them there. So
if you can bring those phagocytes to the
injured area, you can destroy, inactivate
invaders, you can remove any kind of cellular
debris, and you can start preparing for healing.
So let’s take a look at this flow chart.
The leukocyte that automatically will start
phagocytizing as soon as invaders enter into
that wound are your macrophages. So those
macrophages are there, and they immediately
start attacking foreign invaders that enter
the wound. The bacterial invasion itself and
the tissue damage as well can cause the mast
cells to release histamine. Histamine then,
we know, causes vasodialation. So when an
arterial vasodialates that means you have
less resistance, right, and therefore more
blood flow to the injured area. So because
there’s more blood flow to the injured area—that’s
why it becomes red and that’s why it gets
hot. So because there’s more blood there,
that means that you have an increase in certain
plasma proteins that may be important in the
healing process. So these may be clotting
factors, for example, that would prevent you
from bleeding out.
The release of histamine by the mast cells
also increases the capillary permeability.
So what I want you to do is think about a
capillary here, and I’m just going to draw
three endothelial cells that are forming the
walls of this capillary. And when you have
histamine release, the pore size has increased
significantly. So if you increase the pore
size, that means more fluid can flow through
those pores. So that means you’re going
to get a local accumulation of fluid, some
of that fluid being in the interstitial fluid.
Remember that we’ve talked about swelling
or what we call edema, an excess of interstitial
fluid. It can also cause pain, because you
have excess fluid in an area and the skin
can only stretch so much—that causes pain.
Pain is a good thing, because pain actually
forces you to rest whatever part of your body
is injured, and that way it can repair itself
if it’s resting. Because you have this increased
capillary permeability, then that’s going
to increase the number of phagocytes that
can make it to the tissue, like your macrophages.
If you have more phagocytes, that’s going
to increase their secretions. And their secretions
can cause systematic responses like fever,
for example. All in all, then, this is an
inflammatory response and all of the information
in red here—these are all cardinal signs
of inflammation. And all of these cardinal
signs of inflammation are because you had
changes in blood vessel function—the blood
vessel vasodialated.
When we talk about phagocytosis—this is
a form of endocytosis, but specifically, how
is it achieved? So it’s going to be your
job to fill in the steps. Don’t go into
more—any more detail than what these four
steps are asking for here. Opsonins, I do
want you to look at opsonins and, and, why
do we need opsonins? Why are opsonins important
in phagocytosis? Then we have interferon.
This is another type of innate immunity, and
the goal of interferon is to interfere with
viral replication. Now many of you have had
Intro Zoology and so you know that when a
virus gets inside of a cell, the virus takes
over the machinery of that cell. And so it
starts producing it’s own viral RNA and
it’s own proteins. So there are some other
functions of interferon that are listed here,
and go ahead and read them and at this point
realize that there are other functions for
interferon besides interfering with viral
replication. So let’s take a look at how
this will work.
We’re going to take a cell, and it’s
been invaded by a virus. So what the cell
does—
once the cell is invaded by the virus—the
cell is going to be releasing interferon.
So the interferon is going to enter the extracellular
fluid, and it’s going to travel to healthy
cells, cells that have not been invaded by
the virus. And when it binds to these receptors
on an un-invaded cell, this un-invaded cell
now will produce inactive enzymes. So basically
this cell is just waiting, it’s waiting
to be invaded by a virus. Because what these
enzymes will do once they become activated
is they will break down viral messenger RNA
and they’ll inhibit protein synthesis. Now
here comes our virus; it invades this cell.
So those inactive enzymes are now active enzymes.
We’re going to stop protein synthesis of
the virus. So if a virus cannot multiply inside
of a cell, the virus is dead. Viruses rely
on cells in order to make their own proteins,
and they, again, take over the machinery of
the cell. So if they can’t do that they
have nothing to survive on. This is why
we call it interferon. Interferon is interfering
with a virus; it’s interfering with its
replication. So next we have the natural killer
cells.
Natural killer cells are kind of like lymphocytes.
They’re important in the innate response,
and they’re going to release some chemicals
called perforins that we’ll discuss here
in a second. They’re going to target cancer
cells and they target virally infected cells,
and they’re going to lyse the membranes of
those cells. So let’s look at how natural
killer cells work. This killer cell here is
a natural; so it binds to the target cell.
Once they come into contact, the natural killer
cell releases perforins. What perforins do
is they create a pore in the membrane of the
invader. So if we do that then water and ions
can rush in. We increase the permeability.
So if you increase the permeability for water
and ions into the cell, the cell will swell
and burst. It’s going to lyse. Then we have
the compliment system. The compliment system
is activated by two different means. The only
one we’ll discuss here is listed here at
number one. We will discuss number two here
later, but first, let’s focus on number
one when we activate a compliment system.
So here you have a bacterial cell, and on
the surface of it is some carbohydrate. That
carbohydrate is recognized by a compliment
protein. So these compliment proteins are
floating around in your plasma. That’s where
they’re located; they’re in the plasma
cruising around. And when the compliment protein
recognizes this carbohydrate chain, the compliment
protein will bind to the plasma membrane of
this bacterial cell. And once it binds to
the plasma membrane that creates a whole cascade
of events that end up developing what’s
called a membrane attack complex, a MAC. So
this membrane attack complex is essentially
a pore. So once you develop the pore, fluid
can rush into the cell, and then the cell
will burst and it will lyse. So that kills
that target cell as well. So compliments really
good in killing bacterial invaders.
So innate responses are really good. They’re
quick, but they have their limitations. They’re
not specific; they’re not going to kill
specific bacterial species, for example. And
they’re also short-term—they don’t last
very long. So the problem with it is that
because they’re short term and they’re
not specific, then you have to have a smart
system, and that’s what adaptive immunity
is all about. So in the next part we’re
going to start discussing adaptive immunity,
and specifically, we’re going to look at
characteristics of your B and your T cells.
