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    Cellular and Humoral Immune Response to COVID-19


    Long-term protective immune responses to viral infections or vaccines result from the combined actions of B lymphocytes (responsible for humoral antibody immunity) and T lymphocytes (responsible for cell-mediated immunity and assisting B lymphocyte responses). Usually, B cells produce IgM, IgG and IgA antibodies, as well as smaller amounts of IgD an IgE.

    In the specific case of SARS-CoV-2, the pathogen that cause the well-known Covid-19, the focus is primarily on IgM, IgG, and IgA antibodies, which can inactivate the virus by binding to the spike and other membrane proteins and, in that way, prevent infection.

    In this article we will underline the important role of T and B cells (humoral and cellular immunity) to covid-19, as well as their implications and possible contributions to immunology research of SARS-CoV-2 in the future.

    How humoral and cellular immunity fight against covid-19?

    Our body acts against pathogenic organisms (such as SARS-CoV-2) through a coordinated sequential response composed of innate immunity and adaptive immunity.

    Innate immunity is critical to protect against microorganisms in the first hours or days after infection. After this time, the adaptive immune response is activated

    Cellular immunity is mediated by T-lymphocytes; in cell-mediated immunity, micro-organisms and their toxins are attacked directly by cells. T lymphocytes, once the immune response has been activated, will give rise to memory T lymphocytes, so that in future infections by same microorganism, the immune system will be able to recognize it and act more effectively and quickly.

    A successful immune response to SARS-CoV-2 implicates at least four types of T cells subsets that we explain bellow:

    T helper cells (CD4) are responsible for cellular immunity and for helping B cells to produce neutralizing antibodies. CD4 T cells ensure all these components work together by secreting small short acting cytokines that bind to receptors on target cells.

    Cytotoxic or killer T cells (CD8) directly kill infected cells—aided by helper T cells

    Other T cells (including T-17 (Th17) cells) drive the inflammatory responses that help to control infections.

    And regulatory T cells (T regs) which help to contain the immune response, to prevent over-reaction and damage to tissues.

    On the other hand, humoral immunity will do so through antibodies produced by B lymphocytes, which are present in the blood and mucous secretions. B cells are excellent antigen presenting cells to help activate T cells.  Both responses will be crucial in our system protection.

    Like T-lymphocytes, B-lymphocytes also produce memory cells, which means that B cell and T cell types have immunological memory after a first encounter with a pathogen which enables a faster effective response after a second encounter with the same pathogen.

    Do T and B cells protect against future Covid-19 infection?

    Recent developments in Covid-19 immunology pay special attention at the roll of T and B cells in immune response to SARS-CoV-2 infection.

    Scientists worldwide have been working in order to characterize the immune response to SARS-CoV-2, and several studies have been published so far about this, several of them emphasize the importance of B cells and T cells in terms of the progression of the disease.

    In the case of SARS-CoV-2, as well as many other previously studied viruses, the immune response works firstly generating memory B cells that will produce different classes of antibody to inactivate the virus or virus-infected cells. Then our system will produce memory T cells which will support antibody production and also have a direct role killing virus-infected cells.

    In fact, in a long-term follow-up study of people infected with SARS-CoV-2, virus-specific memory B cells were identified early in the course of infection. While serum antibodies reached a peak 20 days after infection before declining, virus-specific memory B cells persisted for more than 242 days after symptom onset.

    Although virus-specific B-lymphocyte and T-lymphocyte responses are evident soon after infection recovering or vaccination, there are other studies that have shown how they have tendency to decrease through time.In this sense, development of new tools is required to understand B-cell and T-cell mediated immunity in Covid-19.

    The importance of B Cells in SARS-CoV-2 serology

    As we have addressed before in this article, B cells or B Lymphocytes are key players in adaptive immune response. Both T cells and B cells have essential roles in the clearance of viral infections, and everything starts with B cells.

    A recent study has shown that B Cell-mediated immunity is vital in the immune response against SARS-CoV-2. In this study total B cells, memory B cells, and total serum IgG, IgG1, IgG2, and IgA levels were shown to be associated with severity and mortality outcomes in patients with COVID-19.

    In this sense, examining levels of B-cell levels and serum immunoglobulin levels of patients during acute SARS-CoV-2 infection could be vital for the early detection of severe patients.

    But how B cells act in order to protect our system against SARS-CoV-2?

    Firstly, this Lymphocytes will be produced soon after the beginning of the viral infection, and B cells will produce antibodies that recognize parts of the pathogen, marking it in order to be eliminated by other immune cells. But the role of B cells does not end here, because some of these B cells are store as memory B cells, and they will be helping the system to start an attack and protect us against the same virus in the future.

    Additionally, the key role of humoral response (B cells response) regarding the control against covid-19 infection is mainly focused on causing plasma cells which produce neutralizing antibodies. These neutralizing antibodies will result in long-term immunity to covid-19 infections and can be used to see if a person has developed immunity to an infection after they have recovered from it. In this sense, SARS-CoV-2 specific memory B are crucial parts in the protective immune memory system.

    Therefore, after infection recovery, plasma cells will continue producing antibodies, which will recognize the viruses in order to fight against them forming serology memory. All of this means that long-term protection is mainly achieved via stimulation of long-lived plasma cells and memory B cells. However, development of protocols and reagents for the reliable detection and isolation of antigen-specific lymphocytes is still a pending challenge.

    Where the research about covid-19 humoral and cellular immunity is headed?

    Covid-19 have created a wide range of severity and symptoms profiles among different people around the world, and for this reason, immune response to this disease have probably also happen in different way between different infected individuals.

    Scientists around the world are still working and looking a way to understand all the mechanisms to be able to fight against this disease. Studies about long term implications of immune response of covid-19 will definitely imply a deeper assessment of T and B cells mechanisms, how much memory cells act to protect our systema, as well as whether and how T and B cells can protect against COVID-19 and what impact they may have on patient progression of disease.

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