Abstract/Details

Cellular characterization of the receptors for the C5a anaphylatoxin and their contributions to the innate and adaptive immune responses


2012 2012

Other formats: Order a copy

Abstract (summary)

Complement is a critical component of the innate immune system tasked with host defense against invading pathogens. Complement also serves a crucial bridge between the innate and adaptive immune systems by augmenting adaptive immune responses, including T cell-mediated immunity. The activation of the complement system leads to the generation of the anaphylatoxins, potent pro-inflammatory molecules. Of the anaphylatoxins, C5a is the most potent and plays numerous roles in innate host defense. C5a mediates its inflammatory functions by interacting with the G protein coupled, 7-transmembrane receptors C5aR (CD88) and C5L2. C5aR is a well characterized receptor that evoked myriad signaling pathways leading to the inflammatory response. C5L2 is an enigmatic receptor that seems to be uncoupled from G proteins and has, until recently, been considered a decoy receptor to limit the actions of C5a. However, recent evidence has suggested that C5L2 transduces functional signals in some settings.

The work herein is to clarify the functions of the receptors for C5a. C5aR has been implicated as a major component of the ability of complement to modulate T cell responses. However, the mechanism by which it does so remains obscure. Part of the difficulty lies in discrepancies within the literature regarding the cellular distribution of C5aR on T cells and related antigen presenting cells. We have developed a novel GFP knock-in mouse model under the control of the C5aR promoter to attempt to clarify this discrepancy. Our results suggest that C5aR signaling is not intrinsic to T cells, but rather functions through a proxy of other innate cell types to evoke functional responses on T cell immune responses. We also attempted to clarify the manner in which C5L2 may transduce a functional signal by examining the G protein coupling potential of C5L2 in a comprehensive fashion.

Indexing (details)


Subject
Cellular biology;
Pharmacology;
Immunology
Classification
0379: Cellular biology
0419: Pharmacology
0982: Immunology
Identifier / keyword
Biological sciences; Health and environmental sciences; Adaptive immunity; Autoimmunity; C5a anaphylatoxin; Complement; Innate immunity
Title
Cellular characterization of the receptors for the C5a anaphylatoxin and their contributions to the innate and adaptive immune responses
Author
Dunkelberger, Jason R.
Number of pages
142
Publication year
2012
Degree date
2012
School code
0175
Source
DAI-B 73/09(E), Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781267351159
Advisor
Song, Wenchao; Manning, David
Committee member
Muzykantov, Vladimir; Sunyer, Oriol; Whitehead, Alexander
University/institution
University of Pennsylvania
Department
Pharmacology
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3508994
ProQuest document ID
1018735435
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/1018735435
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.