In vivo two-photon imaging and computational modeling of dendritic cell-migration and adaptive immune response. Debasish Sen

ISBN: 9781109606881

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NOOKstudy eTextbook

181 pages


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In vivo two-photon imaging and computational modeling of dendritic cell-migration and adaptive immune response.  by  Debasish Sen

In vivo two-photon imaging and computational modeling of dendritic cell-migration and adaptive immune response. by Debasish Sen
| NOOKstudy eTextbook | PDF, EPUB, FB2, DjVu, AUDIO, mp3, ZIP | 181 pages | ISBN: 9781109606881 | 4.49 Mb

Dendritic cells (DCs) initiate adaptive immune response by priming CD4 + T cells in lymphoid organs, via cognate interactions of CD4 + T cell receptors and peptide majorhistocompatibility complex class II (pMHC II) on DCs. Using two-photon imaging weMoreDendritic cells (DCs) initiate adaptive immune response by priming CD4 + T cells in lymphoid organs, via cognate interactions of CD4 + T cell receptors and peptide majorhistocompatibility complex class II (pMHC II) on DCs. Using two-photon imaging we have demonstrated that quantum dot (QD)-based antigen delivery to DCs as well as adjuvant-mediated peripheral DC migration modulate T cell priming and polarization inside draining lymph nodes.

Using computational modeling we have further evaluated whether scanning for cognate T cells by DCs is enhanced by intercellular affinities or chemotaxis. QD-pulsed DCs could be visualized up to 400 microm deep within draining lymph nodes. Moreover, antigen-conjugated QDs enhanced T cell priming by DCs compared to equivalent amounts of free antigen.

These results establish QDs as versatile probes for immunoimaging of DCs and as an efficient nanoparticle-based antigen delivery system for priming an immune response. DC subsets, dermal DCs (DDCs) and Langerhans cells (LCs) are distributed in a tissue-dependent manner, and are differentially mobilized, accompanied by homing to lymphatic vessels, during contact sensitization or after stimulation with adjuvants that induce Th1 (CpG and LPS) or Th2 (papain) responses.

The outcome of subsequent T cell priming and polarization is correlated with site-specific DC distribution and dynamics. Our results imply that LC mobilization is required to support a Th1 response and may inhibit a Th2 response, whereas mobilization of DDCs alone are sufficient to trigger T cell proliferation and to polarize initial T cell activation toward a Th2 response. Our computational simulations showed that increased T cell affinity for dynamic cells as well as chemotaxis mediated by dynamic DCs enhanced repertoire scanning.

Chemotaxis mediated by rigid DCs increased T cell persistence on DCs but reduced scanning efficiency. Thus, energetically favorable alterations in DC-T cell affinity as well as chemotactic mechanisms may be employed by DCs in vivo to enhance stochastic T cell repertoire scanning, and to induce prolonged interactions with T cells leading to efficient adaptive immune responses. Our findings would help in a better understanding of DC biology underlying T cell activation, and would assist in designing vaccines or immunotherapies in future.



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