Biomedical Engineering Reference
In-Depth Information
a
Establishment of infection
- Portal of entry
- heterogeneous vulnerability of mucosal and
epithelial barrier [e.g. 43]
- Target cells
- susceptible target cells are widely spatially
dispersed in the mucosa [e.g. 43]
- focal infections indicate need for close
proximity of target cells [76]
- Spread of infection
- migration of cells to other organs, such as
lymph nodes [e.g. 47]
epithelial barrier
dendritic cell
T cells
activation
b
During infection
(i)
blood
- Compartments for viral replication
- different HIV dynamics, e.g. rates for viral
replication and clearance in different ana-
tomical compartments [27,85,109,127,128]
lung
lymphoid
tissue
liver
(ii)
- Mode of viral transmission
- cell-to-cell transmission (requiring proximity
of susceptible cells) vs. diffusing viral
particles [22,70,113,117]
vs.
c
Immune responses / therapy
(i)
CD8
+
Tcell
- CD8
+
T cells - infected cells
- direct physical contact between immune cells
and infected cells required
infected cell
(ii)
- viral reservoirs
- cell populations capturing HIV virions pre-
venting clearance (e.g. folicular dendritic
cells) [46,48-50,115]
trapped virions
folicular dendritic
cell
(iii)
- Compartments for drug efficacy
- compartments with different rates of drug
efficacy (e.g. drug sanctuaries) [60]
drug effective
compartment
drug uneffective
compartment
Fig. 2
Spatial aspects during different phases of HIV infection: (
a
) establishment of infection,
(
b
) during the infection within a host, and (
c
) spatial aspects of immune responses and therapeutic
interventions. See the main text for detailed descriptions
others [
43
]. Areas where the epithelium is very thin are especially vulnerable to
viral invasion [
47
] and local physical abrasions enhance the probability of HIV to
overcome the mucosal barrier. Accessibility of a sufficient pool of lymphocytes for
replication at the portal of entry represents a second limitation for the establishment
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