Question

Describe the cellular and humoral responses to viral (COVID-19) infection. Be sure to address the role of CD4 and CD8 cells, and the role of B cells and antibodies. What antibodies are produced in response to COVID-19 and when?

Answer 1

The immune response due to viral infection include both innate and adaptive immune response. First the innate immune response is activated which is non-specific including macrophages, dendritic cells and nuetrophils. This non-specific immune response is then followed by the adaptive immune response which includes both cellular and humoral. The innate immunity produces cytokines like interferon-alpha/beta which induces expression of Major histocompatibilty complex (MHC) on antigen presenting cell and activating the cell mediate immune response.

Once a virus has infected a cell and if it starts to synthesize viral protein, some of the viral protein are degraded into peptide fragments which binds to MHC class-I poteins and forms peptide-MHC complexes. This MHC class-I complexes activates the cell mediate immune response. Cell mediate immune response is by T cells which includes helper cell (TH cells) and cytotoxic cells (CTLs) . CD4 cells constitutes the helper T cells and CD8 constitutes the CTLs. The MHC class-I complexes is recognized by the TCR (T cell receptor) on CD8 or CTLs which later cause apoptosis of virus infected cells. During this process the MHC class-II proteins also binds to some extracellular antigens forming MHC-peptide complex. This complex of MHC class-II is recognized by the TCR of T helper cells. The helper T cells are of different types like TH1, TH2, T regulatory cells etc. The TH1 cells produces cytokine like IL-2 (Interleukin-2), Interferon (INF) gamma and TNF ( Tissue necrosis factor) as a response of viral infection. Here the interferon gamma has found to have direct antiviral activity whereas the IL-2 promotes the production of more CTLs. The Th2 cells, produce mainly IL-4, IL-5, and IL-13 which activates eosinophils, basophils, mast cells, and B cells.

The T helper cells further activates the humoral response by activating the B-cells. Activated B cells further diiferentiate into memmory cells and plasma cells. The plasma cells are the ones which produces the immunoglobulin/antibodies. these plasma cell differentiates to produce specific antibodies against the antigen. There are 5 classes of antibodies; IgA, IgD, IgE, IgG, and IgM which are defined by the amino acid sequence of the heavy chain. Of these 5 types IgG, IgA, and IgM are commonly produced after viral infection. During the primary infection IgM is first produced followed by IgA which is produced on the mucosal surface and then IgG is produced in the serum. Here the IgG is found to be very stable and is major antibody produced during viral infection. Hence IgM and IgG is used to diagnose COVID-19 in patients.

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