HPV Innate Response

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

The innate immune system is the body’s first response to infection. When the body is breached by a pathogen, cells called leukocytes engulf, or phagocytose, the bacteria or virus. Since there is a wide range of viruses and bacteria, which are constantly evolving to escape their hosts’ defenses, leukocytes that would recognize specific pathogens would not be very effective when encountering a different type or strain of pathogen. Instead, leukocytes recognize general characteristics that are common to most pathogens, called pathogen-associated molecular patterns (PAMPs). This way, the body does not have to expend energy in generating and maintaining a wide variety of leukocytes that would quickly become obsolete in their fight against infection. Another type of innate immune cell, the natural killer (NK) cell, helps destroy papillomavirus-infected keratinocytes (Scott et al. 2001). NKs are more effective against infected cells in which the virus has begun to synthesize the L1 coat protein (Oldak et al. 2004).

Upon recognizing the pathogen, leukocytes also release soluble chemical signals –cytokines – which signal other leukocytes, NK cells, and cells involved in adaptive immunity to move to the infection site. Cytokines produced by keratinocytes, namely class-1 interferons (IFN-α and -β), tumor necrosis factor (TNF), and transforming growth factor β (TGF-β), can slow or impede the papillomavirus’s growth through the autocrine signaling of the infected cell. As well, NKs must be activated by these and other cytokines in order to recognize infected cells; un-activated NKs do not appear to have an effect on most infected keratinocytes (Woodworth 2002). Research into these effects has shown, however, that the cytokines' inhibition ability fluctuates with the virus’s growth stage, although there is definite evidence that they lose their effectiveness once viral tumors become malignant. Malignant cells thus also resist NK destruction (Evans et al. 1993). The virus also attempts to evade these many effects of cytokines by downregulating their expression and secretion in the host cell (Scott et al. 2001).