"The results from a study show age-dependent expression of ACE2 in nasal epithelium, the first point of contact for SARS-CoV-2 and the human body,"
Man må skjønne at ACE2 er viktig i immuneresponser mot virus, først og fremst.
Og de finnes i ulike steder av kroppen. Det de har funnit, er mindre antal ACE2 i "nasal epithelium" hos barn, og mer ju eldre man blir. Der skjer første kontakten med Covid-19.
SARS-CoV-2 trenger ACE2, for at komme inn i kroppen, først og fremst. Når den vel er inne i kroppen hemmer, deaktiverer, Covid-19, ACE2:s arbeid.
ACE2 genen er en så kalt "escaped gene". Den kommer fra kvinnen. Det er en x kromosome gen. Kvinner har dobbel oppsett av alt da de har to (XX) og menn har bare enn (XY)
Kvinner får/arver sin ene X kromosom fra mor, og sin andre X fra sin fars mor. Farmor.
Hvorfor den kalles "escaped gene" er for at i kvinnen blir en av kromosomerna (X) deaktivert i dna. Sånn att de bare har 1 oppsett av alle gener. Dette skjer i embryot.
Men ACE2 tilhør en av generna som av noen anledning kommer undan denne prosessen. Finnes flere.
Så kvinnen har 2, ACE2 typer, aktiva i sin kropp. Dette ser man som en stor fordel i kampen mot virus/patogener, da mannen har bare 1 type av ACE2.
Noen varianter av ACE2 "matcher" proteinet som Covid-19 benytter seg av for og ta seg inn i kroppen bedre enn andre varianter.
Man har forsket på forskjeller på typer av ACE2 og funnit at Italiensk population og Asiatisk population har en ACE2 type som Covid-19 lettere tar seg inn gjennom.
"in females’ cells, 50 percent are going to be using likely a slightly different version of the ACE2 than other cells. It’s much more difficult for a strain of corona to have a spike protein that could equally infect both populations of cells"https://www.discovermagazine.com/health/the-reason-more-men-die-from-covid-19-may-lie-in-their-chromosomes
Litt annen historie i mellom det, betakoronavirus kommer fra Flaggermusen, men ACE2 kommer fra foreldrene: ( blir litt sånn, når man surfer og tenker! :
De som er eldre, og mest sårbare er fra 70-90 år og oppover. De føddes på 1930-50 tal. Deres foreldrer levde da i tiden fra, 1910-1930. Dette var en stor tid for luftfart (Pioneer era,1903-1914) Santos-Dumont tegnet, bygde og fløy det første praktiske styrbare luftskip.
The Santos-Dumont's, Demoiselle (nr.19) was a series of aircraft built in France by world aviation pioneer Alberto Santos-Dumont. The name of the Demoiselle aircraft is a synonym for "jeune fille"—young girl or woman—but also the common name in French for a Damselfly (vannymfe) The Demoiselle No 19 could be constructed in only 15 days and became the world's first series production aircraft.
"jeune fille", Adolescens (lat adolescere = (att) växa upp, tillväxa) är övergångsperioden mellan att vara ett barn och att vara vuxen; åren efter puberteten. Demo: (music), a song recorded for reference rather than release
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19)
The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once.
These 4 are the
-the hyperinflammatory loop
-the non-canonical renin-angiotensin system (RAS) axis loop
-the hypercoagulation loop
The viral feedback loop includes evading the host’s innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response
The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(17)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS
The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.
..."Sometimes the pathogen (virus) could be a mere initiator more than an actual perpetrator and it is the host’s (patients) forces unchained by the pathogen’s presence, those which are to cause tissue and organ damage.
The first horseman: a sneaky virus (viral loop)
SARS-CoV-2, like SARS-CoV, requires the ACE2 as a receptor to enter the cells.
After the virus entry, the RNA genome (of virus) is released into the cytoplasm and translated into two polyproteins and structural proteins. The survival of SARS-CoV in host cells is eased by strategies to evade the immune response.
- SARS-CoV induces the production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles.
What are PAMPs and PRRs?
Summary: The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs).
- Furthermore, several structural and nsps encoded by SARS-CoV and MERS-CoV antagonize antiviral innate immune response. Interferon (IFN) and interferon-stimulated genes (ISGs) responses are counteracted
What do interferons do in the immune system?
Interferons are proteins that are part of your natural defenses. They tell your immune system that germs or cancer cells are in your body. And they trigger killer immune cells to fight those invaders. Interferons got their name because they "interfere" with viruses and keep them from multiplying.
This sequence of events, namely AECs infection, IFN signaling inhibition, and free viral replication depicts the viral vicious loop.
It was not long before aircraft were shooting at each other, but the lack of any sort of steady point for the gun was a problem. The French solved this problem when, in late 1914, Roland Garros attached a fixed machine gun to the front of his plane, but while Adolphe Pegoud would become known as the first "ace", getting credit for five victories before also becoming the first ace to die in action,
The second horseman:
a gathering storm SARS-CoV-2 infects primarily airway and alveolar AECs, especially type II pneumocytes, the cells that produce alveolar surfactant and are predecessors of type I pneumocytes. However, it can infect any cell expressing the receptor ACE2. SARS-CoV-2, in the face of unchecked replication because of dampened innate immunity, can replicate in high titres early after the infection.
Uncontrolled viral replication, because of a delayed innate immunity response, will cause cellular damage leading to an overexuberant and dysregulated immune kickback. This hyper reaction affecting the innate and adaptative immune responses will pave the way for immune-mediated damage of tissues and organs.
The third horseman: a helpless lung
Once SARS-CoV binds to its receptor, the abundance on the cell surface, mRNA expression, and the enzymatic activity of ACE2 are significantly reduced.
Ang II activates several cellular functions and molecular signaling pathways related to tissue injury, inflammation, and fibrosis. They involve calcium mobilization, free radical generation, activation of protein kinases and nuclear transcription factors, recruitment of inflammatory cells, adhesion of monocyte and neutrophils to endothelial and mesangial cells, upregulation of adhesion molecules and stimulation of expression, synthesis, and release of cytokines and chemokines.
The counterregulatory ACE2/Ang-(1–7)/Mas1R axis negatively modulates leukocyte migration, cytokine expression and release, and fibrogenesis pathways.
The loss of ACE2 results in a overreaction, a uncontrolled immuneresponse against the virus. A cytokine storm.
Resulting in enhanced inflammation and vascular permeability, leaving the lung defenceless in the face of the forthcoming raging cytokine storm.
it is the host’s (patients) forces unchained by the pathogen’s presence, those which are to cause tissue and organ damage.
Axis powers, coalition headed by Germany, Italy, and Japan that opposed the Allied powers in World War II. The alliance originated in a series of agreements between Germany and Italy, followed by the proclamation of an “axis” binding Rome and Berlin (October 25, 1936) Germany, Italy, and Japan now formed a triangle.
The fourth horseman: an epidemic within the pandemic:
Jeg ser et sambånd mellom Covid-19 som kommer fra flaggermusen og utviklingen innen luftfart.
ACE2 som er genen, som vi arvt fra menneskene som levde i tiden for luftfartens begynnelse, er idag "åpen" for en virus fra Flaggermusen.
Ser at i denna tid vi nu lever i, så har vi utviklet flyplan som idag nærmer seg flaggermusens evner (radar etc) Når vi nå nærmer oss flaggermusen evner, ser jeg som en mulighet at just dette er orsaken at vi nå er "åpne" via ACE2 genen, tils vi er i balanse, til og få Covid-19 fra Flaggermusen. Vi "matcher" (frekvensens)
Bat Flight Inspires Next Generation of Wing Design
Så på en måte er våre flyplan flaggermusen, og vi Sars-Cov.
Den dagen vi lær oss at håndtere den, som Sars-Cov kan håndtere flaggermusen idag, i symbiose og uten og skade den.
Frem hit, var ACE2 pilot for SarsCov