Question

8. Illustrate and explain how a virus-infected cell is killed by a cytotoxic T lymphocyte.

Answer 1

Answer: When an immune system recognizes any foreign particle as an antigen, the humoral or cell-mediated immune response is provoked (both components are common in innate and adaptive immunity). The antigen is recognized by specific immune cells where they are processed and displayed on the cytoplasmic membrane. In the case of the virus-infected cells, the antigen-presenting cells recognize, process, and display antigen on MHC class I molecules. When normal cells are infected by microbes or get invariably damaged, they should be killed or repaired, otherwise, it may infect surrounding cells or tissues. When cells are infected with the viruses, the genetic material, and associated enzyme hijack cellular machinery and start to manufacture viral proteins essential for their assembly and further infection. The viral population gradually increases within the infected cell and at a specific point bursts cell and release into the surrounding so as to infect other cells. In this situation, the cytotoxic T lymphocytes (CTLs or Tc cells) recognize/interact with processed antigen displayed on class I molecules These cells start to release enzymes such as granzymes and perforins and kill the virus-infected cells. The activation of CTLs and the underlying killing mechanism can be explained as follows:

The CTL (CD8+) possess granular vesicles filled with enzymes such as granzymes and perforins. When they encounter with virus-infected cells (TCR-MHC class I molecule), there would be cytoskeletal rearrangement by the microtubule-organizing center in the CTLs. In response to this, the cellular organelles align in a specific plane. The granular vesicles fuse with the cell membrane and release the granzymes and perforins. The perforins form pores in the cytoplasmic membrane of the target cell. The granzymes enter the target cells through these pores. There would be pore formation in the mitochondrial membrane through the action of a truncated-BID (break-it-down) proteins. These protein fragments are produced due to the action of granzymes on BID proteins. The mitochondria release cytochrome c due to pore formation and it is the signal for apoptosis. In another process, the granzyme activates procaspase 3 into caspase 3 which in turn degrade inhibitor of caspase-activated DNase. It resulted in the activation of a caspase-activated DNase enzyme that will enter the nucleus and start to degrade the DNA. In this way, the cytotoxic cells kill the virus-infected cells.