Brammer, Clair Elizabeth; (2000) The effects of inflammatory stimuli on antigen processing by dendritic cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

For a vertebrate to survive and reproduce it must be able to fight infection efficiently throughout its life-span. The vertebrate immune system performs this function by recognising, responding to, killing and remembering pathogens. A crucial component of immunity is the dendritic cell, which responds to inflammatory signals such as cytokines which are produced in response to infection. The invading pathogen is captured and partially degraded by dendritic cells via a mechanism termed antigen processing. Dendritic cells are specialised to prime specific T cells against small regions (called determinants) derived from the pathogen by antigen processing. Dendritic cells also control the T cell response towards self antigens, and in this regard, organisms are thought to be most profoundly tolerant to dominant (well-presented) determinants. This thesis is a study of how antigen processing by dendritic cells can be affected by inflammatory stimuli. One cytokine interleukin-6 (IL-6), plays an important role in inflammation and infection in vivo. IL-6 has been shown to dramatically affect the processing and presentation of determinants from a model antigen. In our studies, simple addition of IL-6 had little affect on the processing of various proteins. Dendritic cells activated in vivo by infection with influenza A were investigated. Dendritic cells enriched from the mediastinal lymph nodes of influenza infected mice could present a cryptic (poorly presented) determinant of hen egg lysozyme. Control dendritic cells present only dominant determinants. These data suggest that inflammation may alter the processing of antigens such that cryptic determinants of an exogenous antigen can be presented. This may support the concept that viruses, cytokines and dendritic cells play a role in initiating anti-self immune responses. It may also support the idea that this may be beneficial to the infected host. If the immune system can present many antigenic determinants of a pathogen, it may lead to a tighter control of the infection and in the long term a benefit to the immunological memory of the animal.

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