We're going to be talking now, about,
how, infectious diseases actually cause pathology.
So, this is our final series of kind of slides,
to talk about host microbial interactions.
And this is where we are in terms of our roadmap,
we've talked about the fundamental
concepts of microorganisms,
tropisms and things like that.
We looked at all the different
kinds of microorganisms,
all the way from virus to helminths.
And then we talked about microbial
transmission and host barriers.
Now, we're going to talk about,
well, why does an infectious agent cause disease?
So, there are kind of three
general ways that this can happen,
so, kind of broad concepts to think about.
You can have injury that's
directly related to the infection,
the microbe kills what is infecting.
Okay, that's one pathway.
Another one is, that the injury
is actually due to a robust,
sometimes over robust immune response.
And the third form of injury is related
to subsequent tumor development.
So, those are the kind of the three
ways that you can have pathology,
you can have disease,
associated with an infection.
Let's talk first about injury
directly related to infection.
We see a bunch of pictures here,
just as a a trigger warning,
some of these may not be the most
pleasant things you will ever see,
but you will see things like
this, when you are on the wards
and being good doctors.
Alight, so injury directly related to infection,
you can have a lytic infection.
What is shown here is herpes varicella,
which is also chicken pox and
it will cause a lytic infection,
it will cause the keratinocytes
in the skin to actually lyse
and you get blistering, that
sometimes can be secondarily infected
or can become hemorrhagic, so
a directly lytic infection.
You can have contact mediated
toxicity, so giardia.
Giardia in the GI tract is not invasive,
but as it grazes over the surface of the
epithelial cells lining the small bowel,
it induces malabsorption, so, you
can have a toxicity related to that,
without any particular tissue damage.
You can have degradative enzymes
that are being elaborated,
Ss, what's being shown here, is “Streptococcus,”
you've everyone's heard about
the flesh-eating streptococcus,
well, it's because it's
elaborating toxins and proteases,
that kill the skin and degrade
all of the connective tissue.
You can have endothelial damage and thrombosis,
so, we've talked about rocky
mountain spotted fever before,
but the rickettsial infections,
because they have a tropism,
for the endothelium and smooth
muscle cells lining vessels,
they tend to induce damage in that location,
damage and endothelium,
it's going to have thrombosis
of the affected vessel,
so, you can have injury related in that way.
And you can also have immune suppression,
so, what's being shown on the
right-hand side here is the HIV virus,
which, causes immune suppression by
deleting the CD4 cell population,
the helper T-cells.
You can also have secondary
infections, following say, "Influenza."
If you have an influenza lytic infection,
that's causing obviously damage
of the upper airway, but
those airway epithelial cells,
are very important for keeping out bacteria.
So, secondary infections, say
in the setting of influenza,
are also injury directly
related to that infection, okay.
Let's talk in a little bit more
detail about viral mediated injury,
because viruses can do a number of things.
Here we have a virus that's
binding to its receptor,
it's going to enter the cell,
you're going to get replication
of the viral genome,
we're going to have various proteins,
that are synthesized to make new virus,
we're going to assemble the virus eventually
and then have it exit the cell to
complete the cycle of infectivity.
Every step along the way potentially though,
can be a source of injury.
So, if you're hijacking the host machinery,
you basically take over the normal DNA,
RNA and protein synthetic processes,
the host may not be able to host so
many, they may not be able to survive,
so, that's a direct lytic mechanism.
As you fill up the cell with more
virus and then you rupture that cell,
so, you can release the virus,
that will obviously cause virus injury.
As we've talked previously,
viruses can induce cell-cell fusion
and that abnormal kind of molecular
cellular machinery in a fused cell,
may lead to cell death.
We can have immune mediated injury
and the classic example that
I’ve used repeatedly, is that,
hepatitis B, doesn't particularly cause
any damage to the cell that's infected,
it's when the immune response
recognizes that infected cell
and seeks to clear the infection
by killing the infected cell,
that you have injury, caused
secondarily by the virus being there.
And then finally, you can have
as a result of a viral infection.