fun fact at multiple points in Prime Defenders you can hear TLOU soundtrack as the scenes music! a notable one being in episode 19 when Ashe and Mark get into their little argument after he was shot, you can hear first “The Last of Us (You and Me)” and then a while later you can hear “The Choice” which I feel fit the scenes really well!
The soundtrack has a very specific sound to it that makes it pretty easy to pick out even if it’s made difficult by them talking. It has a twang to it, like old country and folk mixed together with violins and other string instruments that sound slightly out of key, occasionally there are loud bass heavy drums, but i don’t believe they used any of that type in the series.
I am very tempted to go through all the episodes and see if i can pick them all out but it will take literally forever as i have to go through the episodes then if i find an example i have to go through the album and figure it out based off of the sound, and slight differences in the other versions of one track.
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WE HAVE SOLVED THE MYSTERY OF WHY CELLS HATE NEUTROPHILS SO MUCH IN CAW
So, last night, my boyfriend and I got into some random discussion about programmed cell death and some new breakthroughs in medicine, you know, the usual things you talk about with your boyfriend at 1 AM. It is well known that leftover bodies of dead cells are phagocytosed (literally consumed) by macrophages. And that’s why I always wondered why aren’t cells scared of macrophages as much as they are of neutrophils, since neutrophils don’t consume the dead cells. With my limited understanding of immunity (which we technically don’t learn a lot about in biology) I thought that neutrophils only consumed invader bacteria and fungi.
And OH BOY was I wrong about that.
Because (and yes I have spent whole night researching this, I’ll provide the links to papers in the end lol) neutrophils are little freaks and not only do they phagocytose leftovers of cells they actually cause them to die in the first place. This happens during infections, especially with viruses that cause the excess release of cytokines (like Coronaviridae). Cytokines activate neutrophils who basically just follow the signal towards the infection site and there all hell breaks loose. Neutrophils phagocytose bacteria and virions (those are viruses that haven’t infected a cell yet) which is fine, but they also degranulate and NETose. I’ll explain this in simple terms to my best ability.
Degranulation is when granulocytes (neutrophils, eosinophils, basophils and mastocytes are all different granulocytes) release their granules which are kind of like little sacks inside their cytoplasm which contain various chemicals. Releasing these chemicals happens when the cell receives appropriate stimulus, the little granules expel their contents out of the cell’s interior. In the case of neutrophils, granules contain very toxic compounds that cause the formation of free radicals which damage DNA and proteins of the surrounding cells, as well as granules filled with digestive enzymes which, well, digest the surrounding tissues.
NETosis is a special type of cell death specific to neutrophils in which they literally degranulate pieces of their own, or their mitochondrial DNA together with more toxic compounds. This creates a net of DNA strands called chromatin which entangles invading bacteria and severely damages them and also marks them for phagocytosis by macrophages. But this process is not well controlled and some of that chromatin and toxic compounds can land onto neighboring cells which is, as you can conclude, very bad for them.
With these two abilities at hand, neutrophils are very well equipped to kill cells and destroy tissue. Which is good in cases when the cells are infected and the tissue is damaged, but their quite aggressive methods can damage healthy cells in the area as well, some of them will die and neutrophils will phagocytose their dead particles.
Basically, to neutrophils every infection is a huge kill and eat all you can buffet. They literally phagocytose until they physically cannot anymore and then go to the spleen or bone marrow to die. They also allow macrophages to consume them and thus pass on the antigens for antigen presentation which influences further immune response. But they can also cause a lot of damage, especially if cytokine storm happens and they completely lose control. This is what causes SARS and it can kill you if it’s severe enough.
Biologically speaking, neutrophils are very important because they are the first ones to come to the sight of infection and their crazy methods usually finish the things before they get too severe. They themselves produce cytokines that mobilize macrophages and dendritic cells so that more immune cells can join and help them. They also have a role in repairing the tissues they damaged.
However, other immune cells, including macrophages and killer T cells, simply don’t cause as much damage. Neutrophils just go all out, which is why they live for such a short period of time compared to their colleagues (they live for only few days, compared to macrophages who can live up to a month and lymphocytes who can live for months, even years).
So, yeah, my boyfriend and I have concluded (at 4AM this morning) that neutrophils are so feared because they damage tissue, go crazy and violently kill healthy cells by accident, then consume them and that’s not by accident, it’s a mechanism to repair tissues.
I can’t believe I wasted whole night just for this. My boyfriend is also disappointed. But I hope that we finally have an explanation for this mystery. Tell me what you think lol.
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589350/
https://www.nature.com/articles/nri.2017.105
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820392/#:~:text=Neutrophils%20contribute%20to%20tissue%20injury,detail%20here%20(Kruger%20et%20al.
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