Introduction to the Immune Response and Inflammation

The body has many defense systems in place to keep it intact and to protect it from external stressors. These
stressors can include bacteria, viruses, foreign cells, parasites, fungi, these are collectively called pathogens. Other
stressors include trauma, and exposure to extremes of environmental conditions. The same defense systems that
protect the body also help to repair it after cellular trauma or damage. Understanding the basic mechanisms involved in
these defense systems helps to explain the actions of the drugs that affect the immune system and inflammation.

We have 2 line of defense.

First line – is essentially to keep things out. Keep the pathogens out of the body. If these pathogens get into our body,
the first line barrier will kill and eliminate them from our system so that we don't get sick. These are the skin (example are
oils on our skin which are a little bit more acidic which makes it hard for some types of bacteria to thrive in that type of
environment. Next is the mucous membrane where some chemicals are release which makes the pathogen die or
unable to survive, then we even have acidic environments like our stomach acid.
So that's the first line of defense, but we know that that's not good enough, that sometimes these things can get into our
bodies, and there we have to start thinking about the second line of defense. The second line are incharge for the non-
specific and specific immunity. When, I say non-specific or innate, it means that they just generally respond to things that
appear bad. They don't remember the bad things that came before. It doesn't know what type of bacteria it's dealing with.
For specific immunity, our body somehow remembering a virus that it's seen before and being able to respond better to
that virus or that bacteria or that protein the second time it sees it.

In the second line of your non-specific immunity, there are two things. One is an inflammatory response.
When you see blood flowing to a certain part of an area and you see there's pus, what it really is doing is bringing blood
and bringing cells that can fight whatever type of infection you have. It's bringing them to the site where maybe you got a
cut or maybe where a lot of the bacteria or whatever the pathogen is. So inflammatory response is all about bringing fluid
and fighters to the fight. But the byproduct is, that part of your tissue or that part of you body gets inflamed-- a lot of fluid
there, a lot of byproducts of the battle that goes on there. And the other second line of defense is, and it's actually part of
the inflammatory response-- are phagocytosis or phagocytes. So phagocytes are just a class of cell that can eat up
pathogens. They can eat up other things really, but when we talk about the immune system, we're talking about
pathogens. It has some kind of a nucleus, whatever. I don't have to focus on the inside of the phagocyte. It's a traditional
eukaryotic cell, but what I want to do is see what happens when a phagocyte encounters a foreign particle or a foreign
bacteria. So let me say this is a foreign bacteria right here. So the phagocyte, we've already said, is non-specific. What it
does is, it has receptors that respond to just things that it knows are bad. You could imagine these are super sensors.
Maybe these are super sensors for bacteria. The bacteria have proteins on their surface that maybe look something like
that. Obviously they don't look exactly like that. I'm just drawing them as kind of a Y and a triangle so you can see that
they fit. But once these two guys connect-- let me draw the situation where they have connected. So this is the bacteria.
This is the pathogen. And it's really the same idea with a virus or any other type of thing. And we'll actually see in future
videos that these guys can actually be tagged by other molecules, which makes these phagocytes want to attack them
even more. Once they're bonded-- that's my bacteria, the invading pathogen. And now it is bonded. It has triggered the
receptor on this phagocyte. This phagocyte will start to engulf-- it'll wrap around this pathogen. And these two ends are
eventually going to meet. But then once these two meet, what's it going to look like? Then all of a sudden, that bacteria is
going to be completely engulfed. It's going to be inside of the cell. So now the cell-- once these two ends meet and these
membranes merge, then this guy is going to be in his own little membrane bubble-- or you can almost imagine, it's in its
own little vesicle. So this is the pathogen, the bacteria in this case—but phagocytosis-- the process is completely identical
in terms of how it engulfs things. If it was a virus or some type of other foreign protein or any type of really foreign
molecule-- actually, sometimes it doesn't even occur to foreign stuff. It can occur to dying molecules that are not foreign,
that just need to be cleared out. But we'll just focus on the immune system, on foreign things right now. So this membrane
right here will completely merge and go around this guy like this. And of course, you had your receptors and who knows if
they're still there. By the time-- let's just draw them there so you see that that part is that part. But once it's fully engulfed,
this thing is called a phagosome, on which is really just a vesicle that contains that foreign particle that you want to get rid
of. And then other fluid or vesicles that contain things that can eat up this phagosome-- so let's say that this is some
vesicle that contains things—lysozymes and it contains really reactive species of oxygen. And if this comes in contact
with, really, almost any biological compound, it's going to do some damage. But once the pathogen is completely merged
inside the cell, this little package will merge over here and it will
BODY DEFENSES

The body’s defenses include barrier defenses, cellular defenses, the inflammatory response, and the immune
response. Each of these defenses plays a major role in maintaining homeostasis (stable internal state that persists
despite changes in the world outside) and preventing disease.

A. Barrier Defenses
Barriers exist to prevent the entry of foreign pathogens and to serve as important lines of defense in
protecting the body. These barriers include the skin and mucous membranes, gastric acid, and the major
histocompatibility complex (MHC).
1. Skin
The skin is the first line of defense. The skin acts as a physical barrier to protect the internal tissues and
organs of the body. Glands in the skin secrete chemicals that destroy or repel many pathogens. The top
layer of the skin falls off daily, which makes it difficult for any pathogen to colonize on the skin. In addition,
normal bacterial flora of the skin help to destroy many disease-causing pathogens.
2. Mucous Membranes
Mucous membranes line the areas of the body that are exposed to external influences but do not have
the benefit of skin protection. These body areas include the respiratory tract, which is exposed to air; the
gastrointestinal (GI) tract, which is exposed to anything ingested by mouth; and the genitourinary (GU)
tract, which is exposed to many pathogens from the perineal and rectal area. Like the skin, the mucous
membrane acts as a physical barrier to invasion. It also secretes a sticky mucus capable of trapping invaders
and inactivating them for later destruction and removal by the body. In the conducting airways of the
respiratory tract, the mucous membrane is lined with tiny, hair-like processes called cilia which will sweep
any captured pathogens or foreign materials upward toward the mouth, where they will be swallowed . The
cilia also can move the captured material to an area causing irritation, which leads to removal by coughing
or sneezing. In the GI tract or the Gastrointestinal tract (which is a series of hollow organs joined in a long,
twisting tube from the mouth, esophagus, stomach, small intestine, large intestine, and anus) , the mucous
membrane serves as a protective coating, preventing erosion of GI cells by the acidic environment of the
stomach, the digestive enzymes of the small intestine, and the waste products that accumulate in the large
intestine. The mucous membrane also secretes mucus that serves as a lubricant throughout the GI tract to
facilitate movement of the food bolus and of waste products. The mucous membrane acts as a thick barrier
to prevent foreign pathogens from penetrating the GI tract and entering the body. In the GU tract
(Genitourinary System) , the mucous membrane provides direct protection against injury and trauma and
traps any pathogens in the area for destruction by the body.
3. Gastric Acid
The stomach secretes acid in response to many stimuli. The acidity of the stomach not only aids
digestion, but also destroys many would-be pathogens that are either ingested or swallowed after removal
from the respira- tory tract.
4. Major Histocompatibility Complex
The body’s last barrier of defense is the ability to distinguish between self-cells and foreign cells. All of the
cells and tissues of each person are marked for identification as part of that individual’s genetic code. No
two people have exactly the same code. In humans, the genetic identification code is carried on a
chromosome and is called the major histocompatibility complex. The MHC produces several proteins called
histo- compatibility antigens, or human leukocyte antigens (HLAs). These antigens (proteins) are located on
the cell membrane and allow the body to recognize cells as being self-cells. Cells that do not have these
proteins are identified as foreign and are targeted for destruction by the body.