Dynamic Behaviors of Langerhans Cells In Situ




Ward, Brant Russell

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The epithelial surfaces of the body, being constantly exposed to both innocuous and potentially harmful substances and organisms, are protected by an array of immune cells called Langerhans cells (LCs). As a bridge between the innate (non-specific) and adaptive (specific) immune responses, LCs sense injurious stimuli and contribute to tissue inflammation as well as initiate the antibody- or cell-mediated specific responses to pathogenic organisms. These events represent pivotal occurrences in the instigation of the immune response, and thus are important targets for experimental investigatation. To explore the dynamic behaviors of LCs within the epithelial tissues, LCs in living corneal and epidermal tissue were examined ex vivo and in vivo by multiphoton and confocal laser scanning microscopy. LCs at baseline exhibit a unique behavior characterized by rhythmic extension and retraction of the dendritic processes. To explore the responses of LCs to tissue injury, LCs in the cornea and epidermis were examined after pinpoint thermal or diffuse chemical injury. After these stimuli, LCs displayed more active dSEARCH and lateral movement through the tissue. These behavioral responses were dependent on the inflammatory cytokines IL-1 and TNFa, suggesting a requirement for these cytokines in LCs responses to injury. After infection of the epidermis with pathogenic bacteria in vivo, LCs displayed similar responses, showing increased dSEARCH and lateral migration. These results indicate that LCs in different tissues react to varying pathogenic stimuli with common behavioral responses and add a new dimension to our understanding of LC biology.

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The file named "wardbrant.pdf" is the primary dissertation file. Supplemental videos (Movies 1-27) are also provided (in RealPlayer Video format), and more information about each video is available in the file named "Legend.pdf".

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