The complement system and how it relates to what we talked about
with inflammation. Remember when I talked to you about
a silly little story called strawberry and chocolate. This is
opsonin. So C3b is going to opsonize the bacteria
making it mighty tasty for whom? The neutrophil. Then you have
anaphylatoxin C3a. C5a remember is a chemotactic factor.
What does that mean? Once neutrophil comes out in interstitium,
this is the GPS. It will tell the neutrophil where to go.
And the MAC complex, membrane attack complex, C5 to C9 will be
responsible for then boring a hole through the bacteria
in which through osmotic pressure all the fluid accumulates
within the bacteria and it perishes. Important complement.
In complement pathologies, we'll talk about over and over again
including hereditary angioedema. Meaning to say that now
you've lost you C1 inhibitor. Too much complement activation
resulting in oedema in the oral mucosa, inflammation,
difficulty talking. Other complement pathologies that we have
dealt with include paroxysmal nocturnal hemoglobinuria
with the deficiency of DAF and MIIL. That's CD55 and 59 respectively.
Other complement pathologies that you dealt with in microbiology.
If you are deficient of MAC you are now susceptible to Neisseria
species. And another important complement pathology
known as your MPGN type II in which you have a nephritic factor
which then stabilizes my C3 convertase. All of this
we've talked about and all i'm doing is just reinforcing them. And
at this point, with a review, you're thinking, Oh yeah I know this.
Good. Let's continue. Cytokines involved with mediators of
inflammation. We talked about interleukin-1 and TNF
a part of your rolling system. Acute phase reactant. Interleukin-6
plays a pretty big role with fever along with interleukin-1.
Interleukin-6, we have also looked at with what's known as your
anemia of chronic disease. Also cytokines here
release neutrophil from bone marrow. And you need certain
interleukin that are responsible for this. Including interleukin-17.
Nitric oxide is a major vasodilator and also a type of free
radical. It's bactiricidal. Nitric oxide. Remember you want
to do everything in your power in acute inflammation to
vasodilate. Chronic inflammation is where we move on next.
With chronic inflammation, well now let's say that give me an
example here. If it's acute myocardial infarction.
Acute myocardial infarction let's say within the first day,
neutrophils come in. Three days later, the neutrophils undergo
apoptosis and it's being replaced by this cells. We have
lymphocytes and take a look at the specific lymphocyte
that is blown up for you. The nucleus of a lymphocyte should be
approximately the size of your RBC's but here specifically
were in our tissue. Okay. So, lymphocytes and macrophages will
play huge roles and lymphocytes will then be responsible for
well, B-cell will differentiate into a plasma cell. Take a look
at that plasma cell and then within your cell you find
rows and rows of rough endoplasmic reticulum. Because you need this
for proper immunoglobulin production. Chronic inflammation,
the key cells include macrophages, lymphocytes and B-cell abviously
is going to differentiate into a plasma cell. Examples here,
necrosis with chronic inflammation. Fibrosis is going to be more of
an issue. Granulation tissue and immunoglobulin G, IgG.
So the necrosis at this point is more or less contained and it's
more about the repair process. Meaning to say that you are
trying to contain your inflammation. Maybe perhaps a
granuloma is necessary to inprison my foreign body. Maybe TB.
Maybe granulation tissue is required for proper wound healing
which we will talk about upcoming. And if you are dealing with
chronic inflammation the immunoglobulin that you are referring to
always will be IgG in chronic inflammation. With chronic inflammation,
a granuloma. What must you have within a granuloma in which you
would then imprison my let's say a bacteria such as tuberculosis.
Well you must have an epitheloid cell. An epitheloid cell would
be fused macrophages. And by definition you should have at least
three epitheloid cell which is then creating granuloma. Do not
get your granuloma confused with a granulation tissue.
Think about the different places where you can have a granuloma.
With a TB infection, that will be a caseous but nowadays in
Pathology we call this an infectious type of granuloma. And this
granuloma could be located in the lungs, but very well
could be located in other organs including your heart, including
the liver, including the bladder. Or it could be non-caseous
such as sarcoidosis, such as berryliosis, such as Crohn's disease.
All this would then have a granuloma but that would be non-caseous
type. Remember that this for the most part tends to be a type IV
hypersensitivity. And the surrounding cells that you would find
off a granuloma would in fact be CD4 cells. And CD4 cells
specifically it's helper T 1 type in which it's
responsible for conducting or creation or maintanence of a
granuloma. One thing that you want to worry about unfortunately,
is that now as you become more advanced with our pharmacopeia
that you have drugs that are called TNF inhibitors including
infliximab. Infliximab is a major TNF inhibitor in which when it's
used let's say for example autoimmune diseases such as your
such as your rheumatoid arthritis. And if your patient had a TB
infection, you're worried about reactivation. Reactivation of the TB.