HPV Cellular Response

This web page was produced as an assignment for an undergraduate course at Davidson College.

Electron microscope scan of a lymphocyte National Cancer Institute. 2001. http://visualsonline.cancer.gov/ details.cfm?imageid=1944

Part of the adaptive immune system, cellular immunity involves the activation and differentiation of T cells. T cells have one of two major effector functions: cytotoxic killers of infected cells, or helper cells that stimulate other cells to increase their immune functions. They are mostly activated by dendritic cells, which include Langerhans cells (LC). When an immature LC encounters a foreign antigen, it internalizes the antigen and travels to the lymph nodes. There, it presents a naïve T cell with the antigen, causing the T cell to differentiate into a cytotoxic or helper cell, depending on its lineage. The antigens that seem to cause the most T-cell activation in HPV are the E6 and E7 proteins, though this could be due to the fact that latent viruses do not express these proteins. That there are decreased levels of LCs detected in infected epidermis could be due either to their traveling to the lymph nodes or to an unelucidated evasion mechanism of the virus (Scott et al. 2001; Stanley 2006).

If the T cell becomes a helper cell, it must further commit to a T-helper 1 or 2 lineage; TH1 cells signal macrophages to destroy internalized pathogens, while TH2 cells stimulate B cells to produce antibodies against the antigen. The cellular response to HPV is dominated by TH1 cells (Stanley 2006), though it is unknown if clearance of the virus is due to these cells directly. Their importance in the clearance of the infection is demonstrated by the fact that cancerous cervical epithelium has lower levels of IFN-γ, a cytokine involved in TH1 differentiation, than normal epithelium (Scott et al. 2001).

Cytotoxic T cells (CTL), like natural killer cells, help clear the infection by killing infected cell. Infected keratinocytes upregulate adhesion molecules (specifically ICAM-1, VCAM-1 and E-selectin) that help the CTL bind to and kill the cell. (Scott et al. 2001).