Biomedical Engineering Reference
In-Depth Information
￿ To model the processes involved in the early stages of HIV infection in order
to determine important factors for the establishment of infection, and to test and
propose appropriate intervention methods.
￿ To understand the importance of cell-to-cell transmission of HIV relative to that
of infection by cell-free virus.
￿ To explain the different HIV infection dynamics in different anatomical compart-
ments and to reveal the importance of specific compartments during the progress
of infection.
￿ To develop the “full picture” of the HIV disease dynamics by combining each
detailed aspect of the infection and immune processes as it is intended by the
ImmunoGrid -project [ 45 , 99 ].
Advances in computational and mathematical techniques have made it possible
to simulate complex biological processes in detail. This will allow us to address
the computational challenging tasks listed above. However, all these simulation
studies need to be accompanied and validated by experimental data. The already
mentioned two-photon microscopy technique has made it possible to investigate
infection and immune processes on a viral and cellular level in living tissue. It has
revealed the motility characteristics of naıve and activated T cells inside a lymph
node [ 73 , 77 - 80 ] and in the thymus [ 63 , 106 ], and the importance of the stromal
network of fibroblastic reticular cells for the motility and proper activation of T
cells [ 3 , 4 , 35 , 84 ]. Two-photon imaging has been applied to study the interaction
between various hosts and pathogens (reviewed in [ 24 ]), and resulting experimental
data have already been used to enhance and to corroborate computational models of
the immune system [ 10 , 37 ]. There are several other promising techniques which
might enhance our view of immune dynamics in the near future [ 5 ]. However,
despite these advances in observation technology, the newly gained data have to
be accompanied by careful mathematical analysis [ 11 ]. Although in vivo imaging
techniques give us an impression about the dynamics of immune cell interactions
in living tissue, artifacts might interfere with the robustness of the conclusions one
can make. For example, as two-photon microscopy only allows one to observe a
small fraction of the lymph node over time, fast moving cells move out of the field
of observation more readily than slow moving cells, which can bias estimates of the
mean motility and residence times [ 11 ].
Nevertheless, sophisticated computational models supported by experimental
data can help to resolve some of the “known unknowns” in HIV disease dynamics
that are currently preventing the development of a successful vaccine against this
threatening disease [ 122 ].
Acknowledgements Portions of this work were done under the auspices of the U.S. Department of
Energy under contract DE-AC52-06NA25396 and supported by the Center for HIV/AIDS Vaccine
Immunology and NIH grants AI028433 and OD010095.
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