 Hello and welcome to Physiology Open. Do you know that coronavirus has a mechanism to evade our immune system because of which our immune system becomes confused and over-activates creating all the havoc in our body? So basically in this video we will see about the pathogenesis of the disease caused by this novel coronavirus that is SARS-CoV-2. We will see it as two things. One, what the virus is doing to our body and second, what our immune system is trying to do against the virus and in turn start acting against our body. Most common way for the coronavirus to enter our body is through respiratory tract that is via mouth or nose. Our body is equipped with mechanisms to remove any foreign particle like these microorganisms from our body. That is the reason that not all of us get infected with the virus despite being exposed to an infected person. However if we are exposed to more dose of the virus or in case our immune system is not strong as in case of old people or smokers or immunocompromised people in that case the coronavirus manages to reach to the alveoli. Now the further outcome that whether the body wins or the virus wins depends on a tug-of-war between host cells and the virus. So you can very well infer from this that any immunocompromised people the virus is going to win the war right? Anyways once in alveoli, virus encounters macrophages. These macrophages ingest the virus that is phagocytosate. Now macrophages have a very strong bactericidal system but not so good antiviral system. However they can tell other immune cells about the invasion. So basically they call for help. So what they do is that they present a part of this virus to outside on their membrane telling everybody that this is the foreign particle which has invaded us. They actually tell this to helper T cells. This is known as antigen presentation. Also they release certain chemicals known as interleukin 1 and TNF alpha. These chemicals interleukin 1 and TNF alpha increase the permeability of blood vessels causing fluid to leak out of the vessels along with the fluid the neutrophils the T cells start migrating to outside the blood vessels to help the macrophages. So what has just happened? It is the start of development of pneumonia. In fact this is the first stage of pneumonia that is a stage of congestion where a lot of fluid and these WBCs start accumulating inside the alveoli. In the meantime some virion particles attach to ACE2 enzyme present on alveolar cells and enter into cells and start multiplying. Now not only the virus starts using the host machinery for itself it also stops its normal function which is required for synthesis of host protein. So host organelles basically start working for virus and becomes its slave. Now the cells are not easy to give up right? Whenever the cells are infected with virion the immune system starts various mechanism. One the helper T cells to which macrophages have presented the viral antigen start producing something known as interferons. Also these helper T cells help other type of T cells that is the cytotoxic T cells which have the ability to kill the virus infected cells because you see now the cells have become useless they are working for the virus so the body tries to kill the virus infected cell. Not only that the infected host cells are also capable of identifying the antigens of the virus in the cytoplasm like some intermediates in the replication cycle of the virus, lipoproteins on the surface of the virus etc and then they also release interferons. These interferons act on the infected cell itself as well as on nearby cells via jackstack pathway. It is a second messenger pathway leading to changes in the cytoplasm as well as in the nucleus. In infected cells the inhibit viral replication. Also the interferons act on nearby cells and make them resistant to infection by virus so it kinds of create protective ring around the infected cells. So basically we have talked about two things one the cytotoxic T cells and the interferons. Now although these antiviral cytotoxic T cells are crucial for killing the cells infected with the viruses but initial interferon response is very very essential since if it's successful it decreases the number of viruses produced inside the cells and hence decreases the viral load which the T cells have to handle. Now listen carefully the replication of the coronavirus occurs inside something known as double membrane vesicles inside the cytoplasm. So these infected cells are not able to identify that they are infected with the virus since the viral nucleic acid and lipoproteins are hidden inside the vesicle right and thus these infected cells are unable to produce interferons. Also the interference produced by these helper T cells also cannot act on these cells. Why? Because this virus does something more it blocks this jack stat pathway via which the interferons are acting. So what is the end result? The virus keeps on multiplying and hence increases the virus load tremendously. So as virus multiplies inside the cells more and more viruses are released which infect the nearby cells. Now these macrophages they keep on releasing more and more chemicals and activating other WVCs. Because of this you see these chemicals in the beginning we have seen that how they are responsible for development of pneumonia. So there is exaggeration of the pneumonia which is developed. So alveolar edema keeps on increasing because of this the thickness of alveolar membrane increases and hence now oxygen has to cross a thickened membrane. So it takes more time to cross it causing decrease in the partial pressure of oxygen in blood that is hypoxemia and due to oxygen deficiency cells start dying in the body. So that's how people infected with coronavirus come to the infection. Okay thanks for watching the video. If you liked it do not forget to subscribe to the channel Physiology Open. Thank you.