Cytotoxic T Lymphocyte-Induced Apoptosis of a Virus-Infected Cell
MHC-I molecules are designed to enable the body to recognize infected cells and tumor cells and destroy them with cytotoxic T lymphocytes (CTLs). CTLs are effector defense cells derived from naïve CD8 (T8) lymphocytes after their activation by antigen-presenting cells called dendritic cells.
The body marks infected cells and tumor cells for destruction by placing peptide epitopes from these endogenous antigens on their surface by way of MHC-I molecules. CTLs are then able to recognize peptide–MHC-I complexes by means of their TCRs and CD8 molecules and kill the cells to which they bind.
Binding of the CTL to the infected cell triggers the CTL to release pore-forming proteins called perforins and proteolytic enzymes called granzymes. Granzymes pass through the pores and activate the enzymes that lead to apoptosis, a programmed suicide of the infected cell. (Alternately, the granzymes and perforins may enter by endocytosis, not shown here, and the perforins then promote the release of the granzymes from the endocytic vesicle into the cytoplasm.)
Killing of the infected cell by apoptosis involves a variety of mechanisms:
- Certain granzymes can activate the caspase enzymes that lead to apoptosis of the infected cell. The caspases are proteases that destroy the protein structural scaffolding of the cell, the cytoskeleton, and degrade both the target cell's nucleoprotein and microbial DNA within the cell.
- Granzymes cleave a variety of other cellular substrates that contribute to cell death.
- The perforin molecules may also polymerize and form pores in the membrane of the infected cell, similar to those produced by MAC. This can increase the permeability of the infected cell and contribute to cell death. If enough pores form, the cell might not be able to exclude ions and water and may undergo cytolysis. A granule called granulysin can also alter the permeability of both microbial and host cell membranes.
Macromedia Flash Professional 8 was used in constructing this animation. Illustrations were drawn using Adobe Illustrator 10.0.3 and imported into Flash 8.
The first animation demonstrates a CTL binding to a virus-infected cell and delivering perforins and granzymes to that cell.
Slide 1 shows a virus-infected cell displaying viral peptide epitopes bound to MHC-I molecules.
Slides 2 and 3 show a CTL recognizing a viral peptide bound to an MHC-I molecule on the surface of the infected cell by means of its TCR and CD8 molecules.
Slides 4 and 5 show the bound CTL releasing granules containing pore-forming proteins called perforins and proteolytic enzymes called granzymes.
Slides 6 and 7 show granzymes passing through the pores created by perforins and activating the enzymes that lead to apoptosis, a programmed suicide of the infected cell.
The second animation demonstrates apoptosis of the virus-infected cell.
Slides 1 and 2 show destruction of both the cytoskeleton and nucleoprotein of the infected cell and the breaking up of the infected cell into membrane-bound apoptotic fragments.
Slides 3 and 4 show the apoptotic fragments being removed by a macrophage.
1. Abbas, A. K., A. H. Lichtman, and S. Pillai. 2007. Cellular and molecular immunology, 6th ed. Saunders/Elsevier Publishing, Philadelphia, PA.
2. Delves, P. J., S. J. Martin, D. R. Burton, and I. M. Roitt. 2006. Roitt's essential immunology, 11th ed. Blackwell Publishing, Malden, MA.