Biomedical Engineering Reference
In-Depth Information
(such as mycolic acid) of Gram-negative bacteria, and heat-shock protein (HSP)
epitopes that are characteristic of bacteria (1,8). Also see (9) for a discussion of
how bacterial CpG DNA motifs (unmethylated cytosine-guanosine dinucleo-
tides), acting as kill indicators, can guide an appropriate choice between Th1 and
Th2 helper T cells. An example of a harm chemical is a heparin sulfate fragment
resulting from the cleavage of the extracellular matrix by heparanase. Another
possibility is a host-specific epitope of heat shock protein. (1).
To monitor progress toward its two goals, the immune system must be able
to sense the presence of harmful pathogens (which should upregulate the im-
mune response). In addition, sensors must detect harm due to the immune sys-
tem (whose presence should downregulate the immune response). One way to
accomplish this is to assume that the harm H P due to pathogens is represented by
H P = H /(1 + kN ), k a constant,
[1]
where the complement to H P represents the harm H I done by the immune system,
via the noxious chemical N :
H I = H - H P .
[2]
Indeed, we see from [1] that when N is large H P is small and H I = H , i.e., almost
all harm to the host is done by the immune system. By contrast, if N is small, H
H P , and almost all the harm is done by the pathogens. "Killing harmful patho-
gens" can be sensed by monitoring KH P . If KH P is large there is much pathogen
killing (large K ) and pathogens are causing much harm (large H P ). Note that new
information is obtained by combining simpler information. Note also that such
combinations are well within the capability of the complex intracellular interac-
tions that characterize the internal affects of ligating a receptor on a cell surface.
Returning to our simple example, we implement as follows the assumption
that the immune response, in this case the noxious chemical secretion rate s ,
should be elevated by evidence ( KH P ) of killing harmful pathogens and should
be downregulated by evidence ( H I ) that the immune system is causing harm to
self:
sKH
2
p
ss
=+ ++
.
[3]
1
1
sH
sKH
3
I
4
p
(In Eq. [3], s 1 , s 2 , s 3 , and s 4 are constants.) To complete our model, we must spec-
ify the secretion and decay processes that govern the information chemicals H
and K . To that end, let H be produced at a rate that is proportional to the rate h P P
+ h N N at which harm is done to the host, and let K be produced at a rate propor-
tional to the rate aNPE at which pathogens are killed by effectors (compare Eqs.
[A4] and [A2]). Suppose further that both H and K have a finite half-life. In the
Appendix, these assumptions are translated into Eqs. [A5] and [A6] for the con-
centrations of K and H .
Search WWH ::




Custom Search