Infection-induced Immune Injury

00:01 So, kind of wrap things up here.

00:05 How do we get damage, because of an infection? So, there's kind of innocent bystander damage, that can occur, where you have an infection and the response the appropriate response to the infection, because of reactive oxygen species, proteases and other things, leads to local tissue damage.

00:25 You can have, natural killer cell and cytotoxic killing of infected cells, okay, and that's what happens in hepatitis.

00:33 You can have granulomas, so for tuberculosis or leprosy, you can have granulomatous scarring, that is a source of infection, in response to a particular microorganism.

00:45 You can develop cross-reactive antibodies, so again, in the case of streptococcal pharyngitis, you can develop antibodies that cross-react with heart tissue, those antibodies are directed against the streptococcal bacteria, but can cause heart damage.

01:01 You can have cytokine mediated injury, as we just talked about with septic shock and you can form antigen antibody immune complex deposition, that can also be a source of injury, so, there are a variety of ways that we can be impacted by infections.

01:19 So, now that you are a well-trained medical student and you understand kind of how the host immune response, can be directed against various kinds of pathogens, then you can look down the microscope and make a very educated guess about what kind infection is going on, even if you don't have the microbiology cultures to prove it.

01:41 So, I'm going to show you some patterns here and then we'll say what is most likely going on.

01:46 So, in an exudative, acute inflammatory focus or lesion or in an abscess,show it's very likely that you're dealing with a bacteria or a fungus, that has recruited in neutrophils.

02:02 So, the top panel is an abscess in the kidney and that kind of area looks like an explosion with a rim of blue dots, is a, necrotic zone, a pus pocket, an abscess, that has occurred because of a bacterial infection.

02:17 So, when we see exudative things, that is acute inflammatory infiltrates, think bacteria or fungus.

02:24 Again, the lower panel is pneumonia and that alveolus which should be white, there in the middle, is now filled in with a whole bunch of neutrophils and again, I can look at that and say, “More likely than not this is due to a bacterial infection.” If you have apoptosis or cell lysis, it's more likely to be an intracellular pathogen, such as a virus or chlamydia, as we've talked about.

02:50 And what's being shown here, is a, "Herpes varicella," chickenpox blister,bot where we have gotten lysis of all the keratinocytes, they've died and they've left this blister behind, what's also being highlighted is a multi-nucleated giant cell, so, if you see apoptosis, cell lysis and cell fusion with intracellular inclusions, be thinking virus or chlamydia.

03:17 If there is really substantial tissue necrosis, this is a highly virulent organism or it could be an immunocompromised host or it could be rickettsia, which is, actually causing thrombosis and occlusion because of the tropism of that particular bug.

03:35 So, necrosis, can be almost any organism provided that it's highly virulent.

03:41 Granulomas inflammation on their hand, is a reasonably more circumscribed set of possible microbes, that are doing this.

03:51 And what's being shown in the top panel is a caseating granuloma, so a central zone of necrosis, surrounded by a rim of activated macrophages, surrounded by a rim of activated T-cells and what's being shown in the bottom panel is, how this might look grossly, with various nodules of white necrotic material.

04:09 It's called, “Casious necrosis” because, the necrosis looks cheese like.

04:14 So, when we see that, we know those are probably, facultative intracellular pathogens or large pathogens, so that could be fungus or it could be mycobacteria.

04:25 And again, just looking at the pattern, I can be making educated guess and be right, 80-90% of the time.

04:34 Again, coming back to viral infections, interstitial chronic inflammation, so within the interstitium of a tissue here, showing the alveolar wall, with chronic inflammatory cells, it's going to be a viral infection.

04:50 If you have cytopathic or cyto-proliferative changes, so, such as being shown here, that cell that's in the alveolus, it looks like a big owl eye staring back at you, there are actually a couple of them, that's a cytomegalovirus infected cell and we have intracellular accumulations, actually, intra-nuclear viral inclusions.

05:09 So, we can I can look at that and say, “Oh, this is this is cytomegalovirus, I don't have to have a culture.” And if you have eosinophilic infiltrates, by and large be thinking, “Helminths,” be thinking worms, because that's why we developed probably, an eosinophilic immune response to begin with, was to deal with worms.

05:30 So, this is just an example of haematobium schistosomiasis and the organism is there, indicated by the arrow, but surrounding is this impressive rim of eosinophils.

05:42 Okay, finally just to review, infection does not mean that you have disease, right.

05:51 We could technically be infected by a whole bunch of microorganisms and there's no pathology.

05:58 The final boxes, infectious disease, is really, the consequence of both microbial virulence and how the host responds to the microbe.

06:08 And with that we finished our little digression, through immune mediated injury and infectious diseases.

06:17 Thank you very much