Pathology Directly Related to Infection

00:00 Welcome back.

00:02 We're going to be talking now, about, how, infectious diseases actually cause pathology.

00:07 So, this is our final series of kind of slides, to talk about host microbial interactions.

00:14 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.

00:22 We looked at all the different kinds of microorganisms, all the way from virus to helminths.

00:28 And then we talked about microbial transmission and host barriers.

00:32 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.

00:44 You can have injury that's directly related to the infection, the microbe kills what is infecting.

00:51 Okay, that's one pathway.

00:53 Another one is, that the injury is actually due to a robust, sometimes over robust immune response.

01:01 And the third form of injury is related to subsequent tumor development.

01:06 So, those are the kind of the three ways that you can have pathology, you can have disease, associated with an infection.

01:12 Let's talk first about injury directly related to infection.

01:16 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.

01:30 Alight, so injury directly related to infection, you can have a lytic infection.

01:34 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.

01:54 You can have contact mediated toxicity, so giardia.

01:58 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.

02:13 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.

02:30 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.

02:53 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.

03:05 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.

03:22 So, secondary infections, say in the setting of influenza, are also injury directly related to that infection, okay.

03:30 Let's talk in a little bit more detail about viral mediated injury, because viruses can do a number of things.

03:36 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.

03:58 Every step along the way potentially though, can be a source of injury.

04:02 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.

04:17 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.

04:27 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.

04:41 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.

05:04 And then finally, you can have neoplastic transformation, as a result of a viral infection.