let's talk about #CytokineStorm in #COVID19.
1st, there is no standard threshold above which something is called #CytokineStorm.
Mechanistically, the simplest form of #CytokineStorm we can understand is when anti-CD19 #CART cells are infused in tumor-bearing recipients.
1st, there is no standard threshold above which something is called #CytokineStorm.
Mechanistically, the simplest form of #CytokineStorm we can understand is when anti-CD19 #CART cells are infused in tumor-bearing recipients.
in this scenario, we have large numbers of antigen-specific T cells (anti-CD19) and large numbers of antigen-bearing cells (CD19+ tumor cells). When too many T cells engage with too many antigens simultaneously in a short period of time we get #CytokineStorm
Why is that? This is because naturally developing an adaptive immune system (T cells) ordinarily doesn't work that way. 1st, for a given antigen we have very few antigen-specific T cells (~ 50 cells/antigen, unlike anti-CD19 CAR-T cells that are in millions).
These few antigen-specific T cells take time to expand (~3-7 days or even longer) and even after expansion these T cells don't attack the antigen at the same time. This is a gradual process. The first wave of T cells will eliminate some antigen[virus]-bearing cells,
then the 2nd wave and etc. So, ordinarily, the immune system did not reach the level of #CytokineStorm. So, CAR-T cells induced cytokine storm is a man-made event.
OK, in what condition the immune system can develop cytokine storm naturally? One, when superantigen activates T cells nonspecifically. These are special molecules some pathogen produce that engages T cells outside antigen-binding pockets.
These #superantigens can engage many T cells simultaneously. It will produce #CytokineStorm. Does #COVID19 produce #superantigens? Unlikely. Why? because if #COVID19 were inducing cytokine storm through superantigens, every age group would be susceptible the same degree
But #COVID19 susceptibility is very skewed towards the elderly and younger people with metabolic syndrome. We can even say there is premature aging of the immune system in young people with #MetabolicSyndrome.
Still, a superantigen idea is still possible if we assume that aging/metabolic syndrome select/expands oligoclonal T cells recognized by the #COVID19 superantigen.
More, importantly, is #CytokineStorm is a product of innate immune system or adaptive T cells? and if #COVID19 does not have superantigens, how it can initiate cytokine storm?
then we need to come up with a model wherein it takes for innate immune system 7-10 days from the start of infection to initiate #CytokineStorm. Is it possible that unusual innate cells are expanded in elderly/metabolic
syndrome and are recruited after 7-10 days?
syndrome and are recruited after 7-10 days?
Another possibility is that there is substantial delay in T cells priming/expansion in susceptible individuals and then eventually when T cells proliferate and expand and reach target cells there are already too many of them (virus-infected cells)
and just by engaging with them to eliminate infected cells creates cytokine storm like condition.
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