C-INTRAVITAL · Analysing the role of complement in antigen trafficking using intravital microscopy
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-11-01 → 2007-08-31
- EU contribution
- €260,624
- Participants
- 2
- Scheme
- OIF
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Results in brief
Final Activity Report Summary - C-INTRAVITAL (Analyzing the role of complement in antigen trafficking using intravital microscopy)
The immune system continuously faces the challenge of fighting potentially harmful micro-organisms without mounting responses to the human body. These immune responses are orchestrated in lymphoid organs, which are localised at strategic positions in the body. Lymphoid organs bring together cells from the immune system and proteins from micro-organisms in a highly organised and strictly controlled manner. The details of this process remain incompletely understood. In recent years, multi-photon intravital microscopy (MP-IVM) made important contributions to the elucidation of mechanisms of immune regulation in lymph nodes. In the current project we used MP-IVM to study the role of complement in antigen trafficking in lymph nodes. This enabled us to identify a novel mechanism of antigen transport into the beta cell (ß-cell) areas of the lymph node via a system of very fine channels, named conduits. We were able to demonstrate that antigen transport via conduits resulted in rapid activation of ß-cells and display of the antigen on the surface of specialised stromal cells. During the crucial first hours after exposure to pathogens, antigen transport via conduits could therefore be an important mechanism to facilitate the initiation of an immune response to the pathogen as rapidly as possible. The presence of conduits in the ß-cell area of the lymph node had implications for vaccination strategies.
Data: CORDIS, © European Union
Project objective
The immune system is continuously faced with the dilemma of distinguishing between self and non-self antigens. The complement system, a set of more than 20 serum proteins and receptors, is one of the critical components of the immune system involved in making this choice. Upon activation of the complement system in the peripheral tissues by a foreign antigen, complement components are covalently attached to the antigen. Complement receptors on dendritic cells (DCs) and follicular dendritic cells (FDCs) are then involved in the trafficking to, and presentation and retention of the antigen in the peripheral lymph nodes (LN).The detailed microenvironment in the LN, where the antigen is presented to T and B cells, determines whether or not an immune response is mounted. While these general characteristics of antigen trafficking and presentation are widely accepted, the fundamental requirements for complement activation and its role in antigen trafficking have remained unclear. Furthermore, it has so far been impossible to address FDC biology in vivo.In the current project I propose to visualize for the first time FDCs in vivo using novel techniques for intravital microscopy in an FDC-reporter mouse generated in the Carroll lab. I will generate reporter mice for complement factor 4 (C4). I will generate bone marrow chimeras from complement deficient mice, in the FDC- and C4-reporter mice and investigate the cellular source of complement, the location of complement conjugation to Ag, and the role of complement in t he transport of Ag to FDCs in secondary and tertiary lymphoid tissue upon intradermal exposure to Ag. My work will provide new insight into the processes of immune regulation and tolerance.
Original text from CORDIS.
Participants
- VERENIGING VOOR CHRISTELIJK ONDERWIJS, WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG, WAARVAN UITGAAT VU MEDISCH CENTRUM (VU UNIVERSITY MEDICAL CENTRE) · AMSTERDAMCoordinatorCity levelNetherlands
- THE CBR INSTITUTE FOR BIOMEDICAL RESEARCH · BOSTONCity levelUnited States
Links
Data: CORDIS, © European Union