More than 200,000 people died, almost half of the world’s population confined, social and economic consequences never imagined … And all this is caused by a microorganism, SARS-CoV-2, which only measures 120 nanometers (that is, 0.00000012 meters). It is clear that, in immunology, there is no small rival: despite its size, the coronavirus is capable of putting our immune system (and our world) in check.
Although the available data are still limited, knowing the mechanisms involved in the immune response to a virus like this can be crucial to understanding the disease and dealing with it forcefully.
We face a cell hacker
The confrontation between the human being and the virus begins when it enters our cells. For this, it is necessary that the S protein of the virus binds to its corresponding receptor on the cell surface, causing the virus to fuse with the cell membrane.
From this point on, the virus takes control of the cell’s operating system, producing copies of the viral genome like a runaway copier. These copies of the genome are assembled into “little packages” forming new viral particles , which are then released outside the cell and begin to infect neighboring cells.
The replication capacity of the virus is so high that each infected cell can produce tens of thousands of new virus particles. In experiments carried out in mice infected with the SARS coronavirus that emerged in 2002 – it is not usually measured in humans, since lung biopsies would need to be obtained – it was determined that up to 100 million viral particles can be reached per gram of tissue. Multiplying this figure for the average weight of the lung, we could have more than 100,000,000,000 viral particles in each human lung.
Innate immune system, a basic antivirus software
The attack of this hacker is fought by our immune system, which has nothing to envy the best computer security systems. Its operation can be compared to that of complex software made up of cells and molecules. It is classified into two types: innate and adaptive immune systems.
The first is in charge of stopping the attack of the virus in a non-specific way. That is, it detects suspicious microorganisms and keeps them at bay until the “expert computer scientist” arrives, that is, the adaptive immune system.
But how do you keep them at bay? Viruses are intracellular pathogens, which means that they reproduce and hide within our cells . This makes it difficult for the immune system to detect. When the virus infects us, molecules called interferons are produced, which trigger the activation of cells called Natural Killer (NK). These “killers” kill infected cells, disrupting viral replication.
This is followed by other cells of the innate immune system, macrophages and dendritic cells, which “eat up” the remains of infected cells and viruses. With the fragments of the virus exposed on their surface, they travel to the spleen and lymph nodes, where they are “taught” to computer experts: lymphocytes. The result is the activation of those lymphocytes that are specific for the virus.
Adaptive Immune System: The Computer Experts
There are two types of lymphocytes, T and B. T lymphocytes can also be of two types: CD8 or cytotoxic – which recognize cells infected by the virus and kill them – and CD4 or helper T lymphocytes – which coordinate the immune response-. The latter secrete substances that further activate macrophages, NK cells, and cytotoxic T lymphocytes. But they also directly activate B lymphocytes, those responsible for producing antibodies that bind to virus proteins and neutralize them.
The advantage of the adaptive immune system is that it saves memory of pathogens. Or what is the same, it keeps the IT experts on call so that, in the next infection, the response is faster and more efficient. In this way, they prevent the disease from developing a second time. Or, in case it’s unavoidable, they help make it milder.
Being a new virus, little is known about the specific characteristics of the immune response to SARS-CoV2. Hence, for example, the doubts about whether it is possible for recovered people to become infected again.
In this sense, it seems that there is good news: preliminary studies in monkeys suggest that, once they have recovered from the first infection, they do not develop the disease after a new exposure to the virus. And what is even more important, previous studies with the SARS virus – the closest relative of the current SARS-CoV2 – carried out in both mice and recovered humans indicate that there is immunological memory that protects in the long term. These studies suggest that, although the level of antibodies decreases dramatically after one year, the protective response mediated by CD8 T lymphocytes is maintained for several years after infection.
Cytokine storm: when the computer “hangs”
Although our immune system is currently the most powerful weapon we have to fight against the coronavirus, it is being proven that the overactivation of innate immunity is directly related to the severity of the disease. You could say that the antivirus goes crazy and causes the computer to crash.
Translated into medical practice, what occurs in the most serious cases of COVID-19 is an exaggerated increase in secretion of inflammatory substances (cytokines) by macrophages. This phenomenon is called a cytokine storm. The excessive amount of cytokines is toxic to our cells and aggravates lung damage. In addition, in these cases the number of lymphocytes decreases enormously, compromising the effective response against the virus.
Serological tests: access to the source code
A part of the defense against infection is, as has been said, the production of antibodies. They can be mainly of two types: IgM –which are produced during the active phase of the disease– and IgG –which are produced later and are kept in the memory phase.
These antibodies are those that are measured in serological tests and allow us to know if a person is developing an early response and the infection is active (it will only have IgM) or if the disease has already passed for some time (it will only be positive for IgG) .
Seroprevalence studies, such as those launched by the Government of Spain days ago, measure the presence of antibodies in the blood. The goal is to estimate how many people have been infected, have developed memory, and could therefore be protected.
When a large part of the population has a memory against a pathogen, its transmission is stopped, creating the so-called herd immunity. This herd immunity can be achieved in two ways. Naturally, due to the exposure of the population to the pathogen, a slow process that could lead to a much higher number of deaths. The second option is artificially vaccinating the majority of the population. That is why there are so many expectations placed on developing a vaccine as quickly as possible.
Like computer science, the biomedical sciences are advancing at an astonishing pace. Thousands of scientists are working on developing new tools to defeat the virus. We have the capacity, knowledge and motivation to spare to stop the pandemic.
Authors: Marina Bécares Palacios, postdoctoral researcher and honorary professor in the Department of Preventive Medicine, Public Health and Microbiology, Autonomous University of Madrid, and Elena Andrada Romero, Postdoctoral researcher, CNIO National Center for Oncological Research.
This article was originally published on The Conversation. Read the original.
