Hi. Welcome back. The next in this series talks about Host-pathogen Interactions. We're
going to talk about how bugs get in to us and how we will erect barriers to prevent that
from happening. And it's a little bit of, if you were a fan of Mad magazine, it's spy versus
spy. Everytime we erect a new barrier, the microbes are clever and they find a way around
it. So it's interesting give and take and it's given rise to a fairly robust immune system
that we've all developed. But I'm getting ahead of myself. Let's just get in to this talk.
So we're going to talk, this is where we are on our roadmap, and we've talked about the
fundamental concepts, we've looked at all the microorganisms across all the different
phylogenetic areas and now we're going to do the microbial transmission. So, getting bugs
in is a matter of communicability, I mean in the environment or in a particular niche,
they're going to be microbes that exist and will be looking for a way to get in but they
have to be able to survive some place before they climb in to us. So, communicability
actually is a means of thinking about where are they. Transmission involves a number
of ways that they can get in. So, if there's hand-to-hand contact, for example, or
skin-to-skin contact, inhalation to respiratory routes, we can ingest potentially
microorganisms. You can have injections so animal bites, mosquito bites, tick bites, that
sort of thing that allow a direct injection. And then there's vertical transmission, from
mother to fetus via the placenta. So those are routes by which a microorganism might
potentially access its new host. Another issue, very germane to the notion of microbial
transmission is how virulent is the microbe, how many tricks does it have up its microbial
sleeve to be able to access its new host? There's also host susceptibility. So, is the host's
immune intact? Is there good nutritional status? Things like that. There are going to be
host barriers. We're going to talk about host barriers and then how microbes bypass those.
So that's another issue concerning microbial transmission. There is the issue of getting to
your preferred niche, your tropism if you're the microbe and proliferating at that site.
And then, also escaping the host's immune system and not a trivial exercise as will talk about.
And then finally, transmission via communicability in some fashion to the new host. So,
gaining access. This is the issue about microbial virulence. So, how well do you stick to
mucosal surface? How well do you stick to the skin? Adhesiveness is going to be an
important virulence factor when we think about microbial infection. Also, how effective are
you in getting across a barrier? Do you make proteases? Do you make toxins that allow you
to degrade the wall that's in front of you and allow you as a microbe to get in? There are
toxins and proteases that are made that's part of the invasiveness, but that also can
potentially create a local area of injury or necrosis that will be a very good culture
medium for you as the microbe. You have to evade the host responses. We'll come back to
the final slides as we get to the end of this particular talk. We'll talk all about evading the
host response, but there are several kinds of general strategies that we'll talk about here.
One is that you become inaccessible. Think about it. If you're an intracellular pathogen,
unless the cell itself can recognize that you're there, no one can see you're inside.
Or, if you put yourself inside a big cyst, a fibrous wall like some helminths will do, you're
completely inaccessible and you may not be able to go very far but you're there and you're
able to live. There are various proteins that can be made by a microbe that will frustrate
the host immune system. So, protein A is something that will bind up antibody via the FC
portion of the antibody and prevent it from binding in turn to the microbe. So it holds it by
its tale more or less that antibody. And that means the antibody cannot bind to the
microbe, very cool. Or you can make complement inhibitors. You can say "Okay, go ahead.
Do your worst, activate that complement." "No, I'm going to turn those off." So, almost
everything that you can imagine in terms of potential pathways invading the host response,
microbes have somewhere figure that out. Another one is "I'm just going to change my
antigens." So, rhinoviruses, influenza virus, things like that just mutate a lot and once the
host response to one strain, it's mutated to a new one. And those new kind of clones
grow up so you can vary your antigenicity or you can, in a regularized way, just shed your
antigens. So, one trypanosomiasis. What it does is if you have an initial response, antibodies
come in and the bug recognizes that, sheds those antigens and makes completely new ones
that has a new repertoire ready to go. And then you can do immunosuppression. And that's
what HIV does. So, do you mean immunodeficiency virus by causing lysis destruction of the
CD4 helper T-cell population will cause an immune suppressive state that actually is very
clever way, very nasty way, but a very clever way to evade the host response just
eliminate the host response.