Innate Immunity: the first line of defense

Phagocytosis (http://www.peterjurek.com/rbv_site/web_pages/homepage.html) West Nile Virus, one of many causes of viral encephalitis (inflammation of the brain) burst suddenly onto the scene in the U.S. in 1999. Although the virus had been known since the 1930s and is closely related to many encephalitis viruses already endemic in North America, the absence of immunity to West Nile resulted in rapid spread of this mosquito-carried virus. By 2003, WNV was a major topic of public interest in Illinois, where 884 human cases resulted in 64 fatalities1). Bird populations also suffered major losses, particularly among crows and jays. The virus has now spread coast to coast and has probably now joined the list of permanent, endemic encaphalitis viruses in the US. Fortunately, it is causing far fewer cases as more of the population is exposed and develops immune responses.

mosquito.jpgWest Nile Virus is a small, enveloped virus with a single-stranded, plus-sense RNA genome. While the structure and replication of this virus are interesting, this week we want to shift our main focus to how the human immune system responds to the virus. Even though few in the US had ever been exposed to the virus previously, as the virus began to spread, less than 0.1% of individuals bitten by infected mosquitoes developed any symptoms of disease. Of those, most contracted the mild “West Nile fever,” while only about 0.7% developed severe encephalitis. (However, the severe encephalitis has a not-insigificant fatality rate of about 10%!) Clearly, even in the absence of what we would consider immunity, there must be defenses that can thwart pathogens.

Innate immunity refers to defensive systems that are always in place, no matter what kind of pathogen is attacking and no matter whether or not we have encountered that pathogen before. This is different from the antibody response or the cell-mediated killing of infected cells: these are considered adaptive immunity, highly specific protection developed only after an encounter with a particular pathogen; we'll deal with adaptive immunity starting next week. Innate immunity includes barriers to keep pathogens from establishing an infection to begin with, chemical and physical defenses, inflammation, natural killer (NK) cells, and interferon (an antiviral protein). An important component of innate immunity is the ability to recognize an invading virus or bacterium as “non-self” and as a potential pathogen; this has been an especially active area of research in recent years.

Textbook reading

Virology (Carter and Saunders):

  • West Nile Virus, pp. 276-277 (section 21.3.1)
  • Outcomes of Infection for the Host, pp. 105-110 (section 9.2)

Basic Immunology (Abbas and Lichtman):

  • Innate and Adaptive Immunity, pp. 3-4
  • Innate Immunity, pp. 23-43

Key reviews

  • O'Neill, L. A. J. 2005. Immunity's early warning system. Scientific American 292(1):38-45. (Available online through the NCC library–use Find Articles | Browse Journals to find the Scientific American archive and get the PDF version.)
  • Takeuchi, O., and S. Akira. 2007. Recognition of viruses by innate immunity. Immunol. Rev. 220:214-224.
  • Akira, S., S. Uematsu, and O. Takeuchi. 2006. Pathogen recognition and innate immunity. Cell 124:783-801.

Other sources of information

Wednesday's PowerPoint slides

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