| dc.contributor.author | Jawdat, Dunia M. | en_US |
| dc.date.accessioned | 2014-10-21T12:35:55Z | |
| dc.date.available | 2005 | |
| dc.date.issued | 2005 | en_US |
| dc.identifier.other | AAINR08399 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54729 | |
| dc.description | Langerhans cells are immature dendritic cells in the skin their function is capture intruding antigen mature and migrate to the draining lymph node where they present the antigen to T lymphocytes and initiate an adaptive immune response. Mast cells are critical effector cells in innate immunity, however their role in acquired immune responses is less understood. Upon activation, mast cells produce a number of mediators known to aid in the maturation and subsequent migration of Langerhans cells to the draining lymph node. In this study, the ability of locally activated mast cells to induce Langerhans cell migration was examined. Mast cells in one ear pinna were activated using IgE and specific antigen or S. aureus derived peptidoglycan and saline was injected as a control in the other ear pinna. We observed a significant increase in draining lymph node total cellularity and accumulation of Langerin-positive cells in the node draining mast cell activated side compared to control. In W/Wv mast cell deficient mice these responses were absent. However, this response was restored after mast cell reconstitution. Histamine receptor blockade with cimetidine or pyrilamine suggested that histamine is an important mediator in inducing Langerhans cell migration in response to IgE/antigen-mediated mast cell activation but not in response to peptidoglycan. However, experiments using TNF knockout mice suggested an important role of this mediator in response to peptidoglycan. To further examine possible mechanisms of peptidoglycan induced Langerhans cell migration we examined potential molecules or receptors involved. Surprisingly, the Langerin-positive dendritic cell migration response to peptidoglycan was retained in TLR2 and TLR4 deficient mice but was abrogated in complement C3 deficient mice. These data demonstrate novel and distinct mechanisms whereby mast cells participate in both lymph node activation and dendritic cell responses and may provide new strategies for modifying host immune responses in allergic disease and in response to infection. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2005. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Cell. | en_US |
| dc.subject | Health Sciences, Pathology. | en_US |
| dc.subject | Health Sciences, Immunology. | en_US |
| dc.title | Mast cell regulation of dendritic cell migration in vivo. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
