Coronavirus SARS-CoV-2 (golden spheres - false colors) emerging from the surface of cells cultured in the laboratory -
© NIAID-RML
The first sentinels of our body (mucus, cells, etc.) form “innate immunity” which can be supplemented by “acquired immunity” (globules, antibodies, etc.), according to a study published by our partner The Conversation.
Even before birth, the body is already capable of potentially recognizing all the existing “aggressors”.
The analysis of this phenomenon was carried out by Marcelo de Carvalho Bittencourt, professor at the immunology laboratory CHRU of Nancy, University of Lorraine, and Marie Christine Béné, head of the biological hematology department of the University of Nantes.
By impressively saturating resuscitation services and spreading like wildfire on the planet, the SARS-CoV-2 coronavirus, the source of the Covid-19 pandemic, has brutally disrupted our globalized societies.
Publicized as never before, this event gave rise to a thousand opinions on all aspects of the pandemic and how to deal with it.
In the midst of all this media noise, one topic in particular deserves our attention: the way our immune systems cope with SARS-CoV-2, and viruses in general.
What happens in our body when an invader enters it?
First, mucosal immunity
From the tip of our nose to our pulmonary alveoli and from our mouth to the end of our digestive tract, our mucous membranes are in constant contact with the environment.
They are perfectly equipped to locate, tolerate or destroy the elements that pass through their surface.
In fact, the majority of potential invaders (viruses, bacteria, fungi, parasites, various particles, etc.) enter the body through the nose, mouth or eyes, and a large part of them end up arriving in the digestive tract before being eliminated.
This "elimination" uses natural channels for anything that is not absorbed by the mucous membranes.
These "sort" the basic elements of the nutrients that the body needs and leave in the lumen of the digestive tract what is not usable.
It is also in the mucous membranes that the immune responses that target microorganisms begin.
The first barrier of protection involves “innate immunity”.
This includes not only physical barriers, such as the mucus that covers the mucous membranes and entangles certain invaders (also called “antigens”, a term designating any element foreign to the body capable of triggering an immune response), but also cells capable of triggering an immune response. quickly detect danger signals.
These are essentially dendritic cells and macrophages, which are able to ingest foreign elements to destroy them (this internalization is called "phagocytosis").
Dendritic cells phagocytosing porous silicon nanodisks © Brenda Melendez, Rita Serda / National Cancer Institute, National Institutes of Health (via The Conversation)
The varied and globally beneficial microbial flora that lives permanently on all surfaces of our body also participates in immunity.
This flora uses us to shelter it, but also participates in the production of certain food derivatives that we need (for example vitamin K, produced by bacteria present in the intestine).
It also prevents the proliferation of pathogenic microorganisms, while being tolerated by the immune system.
Many antigens detected in the mucous membranes are thus rapidly eliminated.
However, when this barrier is insufficient, systemic immunity, sometimes referred to as "acquired" or "adaptive" immunity, kicks in.
This involves elements of the immune system that are found in the blood: B lymphocytes and T lymphocytes (which are part of the specific "white blood cells" of vertebrates), immunoglobulins (the famous antibodies) and cytokines.
Our “Immunity” file
Sentries prepared before birth
There are two main types of lymphocytes, B lymphocytes, which produce antibodies, and T lymphocytes, which are involved in destroying infected cells, coordinating the immune response and memorizing infections.
All lymphocytes start in the bone marrow, but while B lymphocytes complete their maturation there (B for “bone marrow”), T lymphocytes complete their maturation in the thymus (T for “thymus”).
In addition to their origin, another common point exists between B lymphocytes and T lymphocytes: all of them have the ability to specifically recognize one, and only one, molecular motif present on the surface of potential invaders.
On the surface of lymphocytes there is indeed a particular type of receptor, the “receptor for the antigen” (called BCR for B lymphocytes and TCR for T lymphocytes).
This is complementary to a given antigen: it is able to attach to it, a bit like two puzzle pieces are able to fit together, or like a tenon is associated with a mortise.
What is extraordinary is that even before having encountered the slightest invader, the organism of a newborn baby is already capable of potentially recognizing all the existing antigens.
From before birth, millions of lymphocytes were each endowed with a random antigen receptor, capable of specifically recognizing a single molecular pattern.
Due to the large number of lymphocytes, all existing antigens are potentially detectable: the organism has generated a huge repertoire capable of recognizing everything, "just in case"!
At the time of birth, these millions of young lymphocytes have never encountered any antigen.
They are also called "naive" lymphocytes ... Their immune training begins in the first days of life, by chance of its encounters with the antigens present in the environment.
During this period, while the first multiplication of lymphocytes occurs in her brand new body, the newborn baby remains protected by the antibodies contained in her mother's milk, until her family can take over effectively.
When an antigen enters the body, it sometimes reaches the bloodstream or enters the lymphatic channels that drain lymph (a fluid between cells, which provides them with nutrients and evacuates wastes).
In both cases, the foreigner will find on his way a quantity of B and T lymphocytes stationed either in the spleen (organ which filters the blood), or in the lymph nodes.
When a "naive" lymphocyte encounters its assigned antigen, it begins to multiply.
The number of lymphocytes capable of recognizing this antigen therefore also increases, which is necessary to attack the invaders, which rarely enter the body alone (and which sometimes multiply rapidly).
Some of these new lymphocytes attack the "intruders" and help eliminate them: these are the "effector" cells.
Another part remains at rest, ready to multiply again, quickly during next contact with the same antigen: these are “memory” cells, which allow the body to remember the infection.
B lymphocytes, antibody factories
When a B lymphocyte in the spleen or lymph nodes recognizes an invader by its receptor for the antigen, the BCR, it begins to multiply.
Its innumerable copies begin to manufacture and secrete soluble copies of their BCR: these are antibodies (or immunoglobulins).
Produced in very large quantities, they flow into mucous membrane secretions or into the blood.
These immunoglobulins have the same specific complementarity as BCR.
They can therefore in turn recognize the antigen that induces their secretion, wherever it is found, including very far from the lymph nodes or the spleen.
They thus effectively contribute to its elimination.
Furthermore, with each new stimulation by the antigen, the level of antibodies increases in proportion to the number of proliferating lymphocytes, which continues to grow.
In the early stages after contact with an invader, M immunoglobulins are produced.
They are less specific for that invader than other types of immunoglobulins, and their concentration decreases rapidly.
But they will alert the immune system to the arrival of a new “invader” by trapping it in an immune complex (this expression is used to designate the result of an interaction between an antibody and an antigen).
A human B lymphocyte seen under scanning electron microscopy (false color) © National Institutes of Allergy and Infectious Diseases / National Institutes of Health (via The Conversation)
The first level of "specific" response, that is, the activation of antigen-specific lymphocytes, results in the production of particular antibodies, immunoglobulins A (IgA), which are released within a few hours into the body. mucous secretions by B lymphocytes that have spread throughout the body after being activated.
A little later the immunoglobulins G will be produced, which constitute the major part of the antibodies present in the blood.
They participate in the fight against invaders, notably by interacting with the complement system, a component of the innate immune response.
They are also able to cross the placenta, and therefore protect the fetus.
IgA and IgG are able to bind to invaders and prevent them from entering cells, especially in the case of viruses.
We then speak of “neutralizing” antibodies.
They also attract the attention of other cells of the immune system, such as macrophages, which will “eat” the viruses trapped by immunoglobulins, for example.
The day before T lymphocytes
T lymphocytes also have an "antigen receptor", the TCR, but this is different from the B lymphocyte receptor: it is not an immunoglobulin.
Their TCR enables T lymphocytes to recognize the antigen when the latter is associated with one of the molecules of the HLA system (acronym for “human leukocyte antigen”), which constitute the “major histocompatibility complex”.
Explanation: On the surface of all cells in our body, except red blood cells, are HLA class I molecules (there are three classes of HLA proteins).
These are in a way the "identity card" which tells immune cells that these cells do indeed belong to the body.
When a virus enters a cell, it multiplies there.
This reproduction is not perfect: it generates errors, and some viral proteins are poorly manufactured.
They are then cut into small pieces by a small cellular machinery.
Some of these small pieces of virus (also called "epitopes") associate with HLA class I molecules, and all of them rise to the surface of the cell.
This electron micrograph shows dendritic cells (green - false colors) interacting with T lymphocytes (red - false colors). Dendritic cells internalize antigens, “digest” them and then present fragments of them to lymphocytes © T. Victor Segura Ibarra, Rita Serda / National Cancer Institute, National Institutes of Health (via The Conversation)
If a T lymphocyte passes by, it will find that the HLA class I molecule has been modified (since it is now associated with a viral epitope).
Everything happens as if the cell presented it with a falsified identity card: the T lymphocyte will then react and destroy this infected cell.
In the human species, as in other mammals, the system of histocompatibility is extremely varied, making each individual almost unique.
This means that each of us has a personal way of presenting viral epitopes to our immune system, some doing it more effectively than others.
Like B cells, in the spleen and ganglia, specific T cells proliferate upon recognition of an antigen by their antigen receptor.
However, unlike B lymphocytes, they will not content themselves with generating a single category of lymphocytes, but three sub-populations: helper T lymphocytes, cytotoxic T lymphocytes and regulatory T lymphocytes.
After being activated by the recognition of an infected cell, each of these subpopulations reacts differently.
The helper T lymphocytes secrete numerous "cytokines", chemical messengers of the immune system, which will amplify the response of other lymphocytes, T such as B. Among these cytokines are molecules, some of which are involved in the fight against viruses and bacteria, such as interferons or various interleukins.
Cytotoxic T lymphocytes are in particular capable of killing cells infected with a virus.
Finally, regulatory lymphocytes control immune responses by eliminating or inhibiting the effector T and B lymphocytes which have played their role.
Immune system and SARS-CoV-2
When faced with SARS-CoV-2, which is a new virus, we all find ourselves in the situation of a small child.
Naive lymphocytes specific for antigens carried by this virus exist within our body.
They must multiply to eliminate it and generate an immune memory, which will also need to be amplified for the responses to be more and more effective.
Scanning electron micrograph of a cell (red - false colors) heavily infected with particles of the SARS-CoV-2 coronavirus (yellow - false colors) © National Institute of Allergy and Infectious Diseases / NIH (via The Conversation)
It is therefore theoretically possible to be "re-infected" by SARS-CoV-2, possibly with clinical signs, as long as this coronavirus persists in the environment and our immune system is not yet fast enough to eliminate it. quickly in case of new contact.
However, the different mechanisms of the systemic immune response are most often very effective, especially in subjects who have already been immunized.
They can then be completely silent, and the individual will not even realize that he has been in contact with the virus.
This is the goal of vaccination: to allow an encounter with viral or bacterial patterns in the absence of infection, to train the immune system in anticipation of its encounter with the true pathogen.
When this happens, his lymphocytes will be ready to react quickly and efficiently ...
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This analysis was written by Marcelo de Carvalho Bittencourt, professor at the CHRU immunology laboratory in Nancy, University of Lorraine, and Marie Christine Béné, head of the biological hematology service at the University of Nantes.
The original article was published on The Conversation website.
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