Adaptive Immune Responses and Immunity to SARS-CoV-2

Abstract

Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and translate it to the population of the whole world in record time. Following the infection with the viral antigen, adaptive immune responses are activated mainly by viral particle encounters with the antigen-presenting cells or B cell receptors, which induce further biological interactions to defend the host against the virus. After the infection has been warded off, the immunological memory is developed. The SARS-CoV cellular immunity has been shown to persist even 17 years after the infection, despite the undetectable humoral component. Similar has been demonstrated for the SARS-CoV-2 T cell memory in a shorter period by assessing interferon-gamma levels when heparinized blood is stimulated with the virus-specific peptides. T cells also play an irreplaceable part in a humoral immune reaction as the backbone of a cellular immune response. They both provide the signals for B cell activation and the maturation, competence, and memory of the humoral response. B cell production of IgA was shown to be of significant influence in mediating mucosal immunity as the first part of the defense mechanism and in the development of nasal vaccines. Here, we interpret the recent SARS-CoV-2 available research, which encompasses the significance and the current understanding of adaptive immune activity, and compare it among naive, exposed, and vaccinated blood donors. Our recent data showed that those who recovered from COVID-19 and those who are vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Additionally, we analyze the humoral responses in immunocompromised patients and memory mediated by cellular immunity and the impact of clonality in the SARS-CoV-2 pandemic regarding breakthrough infections and variants of concern, both B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.

Keywords: B cell; COVID-19; SARS-CoV-2; T cell; adaptive immunity; cellular response; humoral response; interferon gamma.

Figure 1

The figure shows an adaptive immune response to the first and second encounter with the SARS-CoV-2 antigen (spike protein). Following the first encounter, various antigens go through the process of phagocytosis and decomposition inside the antigen-presenting cells (APCs). APCs fragment the antigen into smaller peptides, which they present on their surface mediated by surface receptors called major histocompatibility complex class II (MHC-II) molecules. The antigens are then presented to several types of cells in the host, among which we emphasize CD4⁺ T helper cells (also B and CD8⁺ cells). B cells which differentiate into plasma cells, secrete antibodies that inhibit the entry of the viral particle into the healthy cells. The activation of T helper cells by APC causes them to differentiate into different subtypes with specific functions mediated by cytokine secretion and cell-to-cell contact. Th2-differentiated T helper cells help humoral responses mature by providing a second signal to B cells, mostly through IL-4 secretion and CD40/CD40L interaction. Some CD4⁺ cells also become T follicular helper cells (Tfh), which govern the important interactions in the germinal centers important for the maturation of memory B cells and long-lived high-affinity antibody-producing plasma cells. Another subset of CD4⁺ T cells differentiates into a pool of memory T helper cells. Th1 T helper cells play a crucial role in cellular response formation. They pivot the MHC-I activation of CD8⁺ cells (CTL, cytotoxic T lymphocytes) by interacting with APC’s simultaneously. Activated CTLs then act by causing apoptosis (by Fasl ligand–FasL binding) of the host cells that are infected with the SARS-CoV-2. Some CTLs differentiate into memory cytotoxic T cells, which have the role of fast restoration of the CTL response with secondary antigen contacts. A similar mechanism of destruction occurs when NK cells interact with the virally infected cell. They contain granules with IFNγ and TNFα in their cytoplasm, which, when secreted, cause programmed cell death. As well, the mechanism of activation of NK cells does not occur through MHC molecules is important because MHC is not always present on the virally infected cells.