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Infection response is definitely quite fine tuned. But that fine tuning could get counteracted if, for example, someone has mutations that result in a higher ratio of TNF to IFN-g during infection, potentially even exacerbated by a double dose of TLR7. If B cell expansion is dependent on some...

It would increase likelihood of autoreactive clones getting activated in spite of peripheral tolerance mechanisms. That event can either get counteracted further downstream, or eventually spiral out of control into autoimmunity through the additional steps I mentioned before. But its a necessary...

You're right, full-blown autoimmunity will involve additional steps like further expansion of autoreactive clones, plasma cell differentiation, and even production of different clones that recognize the same antigen with higher affinity. Bystander activation, if its real, probably happens to...

Right, and sepsis involves cytokines at different proportions and concentrations than you would see in a run of the mill influenza infection, some of which actually work to modulate lymphocyte activation and development and might make autoimmunity less likely. Like I said, I don't think...

I think the point is that it’s not virus-specific at all, except for some cases of cell type specificity dictating where the infection takes root Thanks? I’m not saying I think this is probably the correct answer but I’m open to the idea because the specifics of what is being proposed wouldn’t...

Every person has a number of autoreactive lymphocytes that bypass central tolerance. A lymphocyte that recognizes any antigen has to pass through certain checkpoints in order to start causing a fuss, and that gets helped along by signaling molecules from other immune cells. In most people, there...

I'm not sure that epidemiology would provide much evidence if some combination of predispositions are needed in the first place for infection to tip over peripheral tolerance mechanisms. The relevant comparisons would be taking people with similar genetics and seeing if people exposed to viral...

I've seen presentations on the mouse work and I know translational studies are in the pipeline. If it's just a fluke from the animal models I'm sure we'll know soon enough. But as it stands it does seem a more plausible explanation for things like post-viral thyroiditis and T1D following influenza

If a project is well funded and comprehensive enough there will usually be a biostatistician collaborator who does the analysis and (hopefully) knows to account for these things. But often when you have a smaller investigation like this study, its just going to be a grad student or post doc...

That's the idea EBV would be somewhat of a different case since EBV directly infects the B cells that drive autoimmune disease. The recent studies didn't definitively prove that EBV is a culprit (in my opinion) but they do show some hints that latent EBV changes how B cells function in a way...

Most researchers I know interested in this are not looking into molecular mimicry so much as bystander activation, where viral infections provide a permissive environment helping to bypass peripheral tolerance in individuals already poised towards developing autoimmunity. So the formation of the...

yup, my program only requires one very basic stats course (I’m taking more advanced courses because I’m specializing in bioinformatics, everyone else is doing biology). I don’t know if the idea of pseudoreplication would even be brought up in that basic course You’d hope that scientists absorb...

I’ll note that the analysis methodology looks sound to me. On the more stringent side, which I appreciate

Completely understandable. If B cells investigations gain more interest from the Dara trials then we might get an incidental answer to the question of “global vs antigen-specific shift” anyways from other findings Anytime! I would hardly claim B cell expertise but happy to toss around ideas...

Just starting to look through the paper, thanks for your work @DMissa @MelbME and everyone else involved. My interpretation is along similar lines—increase in lipid synthesis across the board is most easily explained by passage through B cell developmental checkpoints (as certain epigenetic...

I did say above that aquaporins offer selective passage to water and other small solutes. AQP1 is the main one with affinity for CO2 I’m remembering correctly. And there are several hundred various ionic channels Evolving an additional layer of astrocytes around blood vessels “results” in a gap...

Sure, me too, I’m pretty sure that is what the goal of research in that area is aiming for. It may be overhyped but I do think it is ultimately good to fund exploratory research into an unknown facet of brain anatomy. it’s not? The reason to talk about aquaporins at all is because the...

Again, they might not be the driving mechanism of some pumping motion but would be able to establish an osmotic gradient. The question of how does need to be answered, I agree. I’m not arguing that these systems must be relevant, just that their functioning is not inherently implausible and...

Well they are already there on every other blood vessel in the body so presumably they serve some purpose or otherwise aren’t detrimental enough for vessel function to have been acted upon by negative selection

Unless each various system accounts for some proportion of necessary waste clearance and a 15% reduction does have negative effects when it can’t be adequately compensated by other methods (or not compensated without other negative consequences)