Question

Type a 500-600 word response to this topic to be submitted for assessment:

While an immune response to a pathogen such as a Covid 19 will involve many features of immunity we have learn about, a critical aspect will be the T cell response. T cells, once activated can differentiate into one of the various effector T cell subsets that are known and in particular to this conversation, the CD4 T subsets, Th1, Th2 and TH17 cells and the CD8 cytotoxic T cell subset.

Now focusing mostly on the adaptive T cell immune response to a viral infection, describe the key immunological events that would occur upon infection with a virus (generic) that would lead to a effective cytotoxic T cell response and how this would assist in clearing the virus.

Answer 1

An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. Proper activation of these T cells depends on professional antigen-presenting cells, such as dendritic cells (DCs).

Once a virus infects a cell, the virus will use the protein-synthesis machinery of the host cell to synthesize its own proteins. During this process, some of the newly synthesized proteins will be degraded into peptide fragments and, if they have sufficient binding affinity, bind to MHC class I molecules. These MHC class I-peptide complexes will then be presented on the cell surface of an infected cell and activated CD8+ T cells, specific for the peptide, can recognize the MHC class I-peptide complex and induce apoptosis of the infected cell by releasing cytotoxic granules. Activation of these CD8+ T cells occurs in the draining lymph nodes, where antigen-presenting cells (APCs), such as dendritic cells (DCs), and naïve T cells encounter each other. In these lymph nodes, DCs and CD4+ T cells provide the co-stimulation necessary for proper activation of CD8+ T cells. During the initial phase of a viral infection, there is a significant increase in the number of CD8+ T cells. Priming of these naïve T cells will not only occur through the classical pathway via infection of a cell, directly leading to presentation of peptides on MHC class I molecules, but also through cross-presentation. Cross-presentation enables the presentation of viral peptides, taken up from extracellular sources, on MHC class I molecules. Several different cell types have been demonstrated to cross-present antigens in vivo, including professional APCs such as macrophages and DCs. CD8+ T cells, activated either through the classical or cross-presentation pathway, induce apoptosis of virus-infected cells by the release of cytotoxic granules and the production of TNF-α and IFN-γ. The cytotoxic granules contain perforins, granzymes, and granulysin. Perforins aid in delivering contents of granules into the cytoplasm of the target cell. Granzymes, such as granzyme B, and granulysin activate apoptosis of the target cell. TNF-α can interact with the TNFR-I receptor, which induces apoptosis of infected cells. IFN-γ is an important cytokine in the immune response to various viral infections, since it can induce an antiviral state in uninfected cells and enhance the cytotoxic function of CD8+ T cells. By the classical antigen presentation pathway or by the cross-presentation pathway, any form of virus can be presented on MHC class I and MHC class II and thereby stimulate antiviral responses by both CD8+ T cells and CD4+ T cells, respectively, leading to a broad cellular response to infection. After infection, some of these activated T cells will develop into memory T cells. In the event that a secondary infection occurs, these cells can rapidly mature into effector cells and respond to infection.

During chronic viral infections, when the host is not able to clear the virus, the main role of cytotoxic T cells is to limit disease severity and delay disease progression.