Host Barriers: Immune System

00:00 Finally, if you've been successful in getting across any of those barriers and you're wandering around in the body finding the niche that you like best using your tropism to go to the tissue that you prefer, you also have to evade the immune system. And as we've talked about in previous lectures, the immune system is a pretty robust mechanism by which we can clear invaders and we have developed many redundant and overlapping methods to deal with them. So you have to be pretty darn clever if you're going to be a bug to evade them. Let's talk about kind of the mechanisms. So, antibodies will work very well for extracellular pathogens and they can neutralize them, that is bind to them and prevent them from being infective. They can activate complement so they punch holes in those microorganisms. They can opsonise antibody bound to the microbe, can opsonise the microbe and make it tasty so it gets phagocytosed by neutrophils or by macrophages. And then there is the antibody dependent cell-mediated cytotoxicity, ADCC, where natural killer cells can kill where an antibody has bound. And then there's cell-mediated immunity as well and this is going to be largely for intracellular pathogen. So we have cytotoxic T cells, we have macrophages that can eat and engulf a cell that has been infected. We had natural killer cells that can kill infected cells, and eosinophils particularly for helminths, for worms, are going to be important cellular elements. So we've got antibody and we've got cellular components that are going to be the host barrier at the level of the immune system.

01:51 Alright, now I'm a bug, I'm faced with all of this very potent opposition. What do I do about that? So, we're looking at a couple different bugs here, the orange barge represent extracellular bacteria for example and the kind of blue icosahedrons represent virus.

02:11 So, one thing that you can do if you're a bug and then you want to be successful and you're in the outside world, that bacteria can inhibit phagocytosis. And you can inhibit either the ability of the invading macrophage or neutrophil to bind you or to engulf you. So that's one mechanism by which you can evade them. You can also, even if you've been successfully ingested, you can evade having the lysosome fused with the phagosome and you won't be killed and you'll be able to happily reproduce within the phagosome. And that's another mechanism that microbes use. Very clever. If you're a virus, on the other hand, you have gone into the cell and you can do a number of things to the surrounding immune response. So here we have a virus that's gotten in and part of the viral genome is to make something that looks like an inhibitor for the immune response. So, for example, Epstein-Barr virus can make an IL-10, interleukin-10-like analogue that will turn off elements to the immune response. That's very clever. So those with the little dots, making something like that. Then, that infected cell containing that microbe making that IL-10 analogue will be completely left alone. You can also turn off the expression in your invaded cell of MHC, the major histocompatibility complex molecule. And if you turn that off, then the cell can no longer tell the outside world "Hey, I'm infected," because it's no longer expressing the MHC molecule. And you can also have more basic, more general effects on gene transcription so that you can turn off many of the other mechanisms through effects directly on the host genome. So, evading immune system involves a number of things including ones we just talked about but you can change your antigens. So, that's what influenza does. Or you can look like the host. Oh my goodness that's a very clever thing. Yeah, we'll it's a schistosomiasis kind of cloves itself in host proteins and it's like a wolf in a sheep's skin.

04:33 And it can just hang out because immune cells that go by go "Hey that looks like the big self" and they ignore it. So it's very clever actually. You can remain inaccessible so we talked about intracellular pathogens. We also talked about cysts. So if the immune system can't find you, it can't get rid of you. You can frustrate the immune system. So we talked about that protein A that holds the tail of the antibody away from itself, that's very clever. But you can also have things that diffuse the complement system or inhibit the complement system. Or have ways to escape the phagosome. So that's going to frustrate the immune system altogether. You can inhibit antigen presentation as we talked about where you suppress the expression of MHC molecules. You can suppress the immune response. Again, we've talked about HIV AIDS where you're basically killing off the CD4 population. But suppressing the immune response might also be making an analogue to interleukin-10, very clever. And then, you can make things that look like host and you can make soluble receptor homologues that will allow the host to think it's getting rid of you, but in fact it's just a decoy. So with that, we've talked about how bugs get in and then how we can erect barriers and then how the new clever microbe can evade those barriers.