Global Immunospeaker

@dkledezma @globalimmuno Thanks Debbie. Yes we would expect avidity to increase as the receptors cluster. This might be an important characteristic but difficult to study directly. Important to consider in generating the next generation of ISAs

@globalimmuno @immunospeaker Such an interesting talk! For the low affinity approach, as the target protein clusters, is the avidity of the antibody expected to be higher? How informative would avidity be compared to avidity when your tram designs these engineered antibodies? #globalimmuno

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@dkledezma @globalimmuno Thanks Debbie. Good question - yes, we would expect that as clusters form the local membrane concentration is effectively higher, allowing for avidity effects. Difficult to study directly but definitely part of the equation for designing the next generation of ISAs

@ShubhaChiplunk1 @globalimmuno For later time points, we are actively looking into this at the moment: What lung tissue factors act on the recruits to change their phenotype and how.

@ShubhaChiplunk1 @globalimmuno without necessarily needing and additional signal.  On day 28, the functionality and cytokines produced are still pretty similar, and we are testing if IFNg and other obvious suspects are required for maintaining this reactivity.

Please ask questions for today's Global Immunotalk by Andreas Wack HERE by replying to this tweet. Don't forget to mention #globalimmuno. Andreas will use the account @immunospeaker to answer questions.

@KatiaRJesus @globalimmuno So if your question above is, would you see a MPh imprint in the peritoneum after a lung insult, we have not found this, for us meaning that the BM imprint may not happen or be relatively minor – but to be tested rigorously.

@KatiaRJesus @globalimmuno The implication of this is that there should be an effect across organs (an imprinted monocyte should go anywhere in the organism), but we did not observe this post influenza when we tried this.

@KatiaRJesus @globalimmuno Yes I would.

@KatiaRJesus @globalimmuno so your “resident comparator” may itself be higher on the reactivity scale than alveolar MPhs – something to explore!

@KatiaRJesus @globalimmuno recruit new cells in, these new cells might be more responsive than the original population. However, the differences may be more blurred than in the lung, as the monocyte contribution to peritoneal cells at steady state is thought to be higher than in the lung,

@VitalyGanusov @globalimmuno However we did not deplete them away so it could still be that they are part of the pathology. Good point.

@VitalyGanusov @globalimmuno We considered this possibility as it is known that over-exuberant CD8 responses can be pathogenic – but we did not find any difference in the CD8s from 129 wt versus IFNAR1 KO mice in terms of numbers of Ag-specific cells, activation, perforin expression etc.

@XimenaRaffo @globalimmuno We also don’t know where and how and why the few survivors that re-form the subpopulation of resident AMPHs survive and if there is anything special about them.

@XimenaRaffo @globalimmuno Thank you! Two great questions and we don’t have the answer: Resident AMPHs disappear quickly and we don’t know why and where, and whether infection is required for this (my hunch would be: no).

@chjohnston11 @globalimmuno monocytes develop from this precursor, get to the periphery and are recruited into the lung – not impossible but very tight. For the monocytes we should have a look.

@chjohnston11 @globalimmuno after that time window the lung is “full” again, niches are filled and there is no availability of niches. That means that in this small time window a signal needs to travel from the infected lungs to the BM, give an imprint to some hemopoietic precursor,