Life or Death: Complement Activation and Response to a Streptococcus pneumoniae Infection
by
Amber M. Smith
University of Utah
Coauthors: Frederick R. Adler, University of Utah, Jonathan A. McCullers, St. Jude Children's Research Hospital, Ruy M. Ribeiro, Los Alamos National Laboratory, Alan S. Perelson, Los Alamos National Laboratory

A Streptococcus pneumoniae infection in mice has three possible outcomes: (i) rapid clearance, (ii) acute infection with clearance, or (iii) acute infection ending in death. Which of these occurs depends on the initial dose of bacteria and their interaction with the complement system, one of the first lines of defense in the immune system. There are three biochemical pathways of complement activation: classical, alternative and mannose-binding lectin (MBL). Initiated by antigen-antibody complexes, bacterial surfaces and MBL, respectively, the complement cascade involves more than 30 proteins which act as opsonizers, anaphylatoxins, and initiators of other components of both the innate and adaptive immune system. The final product, called the membrane attack complex, can lyse and kill pathogens. The classical pathway initiates the response to S. pneumoniae infections, but is amplified by the positive feedback in the alternative pathway. We use differential equations to model the kinetics of initiation and amplification of the cascade, and to identify the factors which determine the outcome of a bacterial infection.

PDF

Date received: May 9, 2008