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4.2
Simulated Bacterial Infection
Bacteria within the tissue multiply; their waste products, produced from a large
concentration of bacteria, can be damaging to the human body. Therefore it is
important that the immune system kills off bacterial invaders before this critical
concentration is reached. The following experiment demonstrates immune system
response processes during bacterial infection. The key players and their interac-
tions are outlined in Fig. 6. As this involves not only bacteria and macrophages
but also neutrophils that enter tissue from the vascular system, the simulation
space comprises a segment of a blood vessel (Fig. 7). The tissue-vessel interface
area is initialized with tissue cells, B cells, helper-T cells, macrophages, and a
number of bacteria acting as infectors. The blood vessel, lined with endothelial
cells, contains red blood cells and neutrophils.
Macrophages that engulf bacteria release TNF (tumor necrosis factor) while
lipopolysaccharides (LPS), which are major structural components of Gram-
negative bacterial cell walls, are released into the tissue area (Fig. 7a). Once
endothelial cells get in contact with TNS or LPS, they release selectin or inter-
cellular adhesion molecules (ICAMs), respectively (Fig. 7b). When a neutrophil
collides with an endothelial cell which produces selectin, it will start to roll
along the interior surface of the blood vessel. A neutrophil rolling along an
ICAM-producing endothelial cell will exit the blood stream and head into the
tissue area. Once in the tissue area, neutrophils—together with macrophages—
act as complementary hunters of bacteria (Fig. 7c). Notice the high number of
activated endothelial cells in the blood vessel wall. A bacterium colliding with
a neutrophil is engulfed and consumed, while LPS and TNF are again released
into the system. Finally, all bacteria have been eliminated and the number of
activated endothelial cells is decreased (Fig. 7d). Neutrophils will soon disappear
since the system has recovered from the bacterial infection.
5
Conclusion and Future Research
The IMMS:VIGO::3D simulation environment is currently used as a teaching
tool in biology, medical, and computer science undergraduate and graduate
classes. Due to its visual interface and the ability to specify many simulation
control parameters through configuration files, it serves both as an educational
device as well as an exploration tool for researchers in the life sciences. Students
seem to gain a more 'memorable' understanding of different aspects of immune
system processes. Although visualizations can also be misleading, they usually
help in grasping essential concepts, in particular in the case of an orchestrated
system of a multitude of agents. Consequently, from our experience, the visual-
ization component is important for a proper understanding of emergent processes
resulting from the interplay of a relatively large number of agents of different
types with simple but specific local interaction rules. Gaining a proper under-
standing and 'intuition' about emergent properties as in the immune system
plays a key role in building today's biologically accurate computer simulations.
 
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