Theoretical Models of Immune Processes - Immunological Computation: Theory and Applications - page 31

2.2.2 Second-Generation Immune Networks

h e second-generation IN (SGIN) refers to a specifi c class of networks that tries to
model natural autonomous behavior of the immune system (Varela and Coutinho,
1991). Experimental and theoretical studies on naturally activated T and B cells (cells
activated without the presence of antigens) shows that natural serum antibodies and
activated B cells infl uence other (activated B and T) cells, whereas resting B and
T cells do not have such eff ects. h e SGIN model postulates that interactions of B
cells in the network are determined by their a nity to preexisting soluble antibodies
and self-antigens and have distinct functional consequences, according to a bell-
shaped dose response curve, which empirically determined it (Varela and Coutinho,
1991). h us, both very low and very high levels of interactions lead to cell death,
whereas intermediate levels of interaction (for increased binding strength) result in

1. Cell survival in the resting state
2. Cell minimal proliferation

3. Cell proliferation with little or no antibody secretion

h erefore, SGINs try to model the immune system's autonomous behavior, that is,
its behavior in the absence of antigens. Also, these models involve the notion of net-
work “dynamics” and metadynamics, which include the rate of production of new
B cells, turnover rates in the resting lymphocyte compartment, and the rates of their
activation and diff erentiation to antibody-secreting plasma cells.
h e main contribution of SGIN model is that it brought two views of the immune
system into compatibility, clonal selection and network theories (Coutinho, 1989).
Although the clonal selection theory tries to explain the specifi city and amplifi ca-
tion of immune responses to external antigens, this IN theory looks for explana-
tions to the way “preimmune” repertoires are selected, how natural lymphocytes are
activated, self-tolerance, and the biology of autoreactive cells.
To summarize, the aspects of SGIN models are as follows:

• INs are made up of B lymphocyte clones, which are connected through
idiotypic interactions. Interactions of these INs with T lymphocytes are
neglected or not considered.
• h e streng t h of activation a nd popu lation dyna mic s of each lymphoc y te clone
is controlled by the strength of receptor ligation in soluble Ig molecules.
• Soluble Ig molecules are the main mediators of idiotypic interactions because
they can rapidly diff use through the body fl uids, in a much higher proportion
than those present as membrane Ig receptors in the lymphocytes.

Other versions of SGIN models (De Boer, 1989; Neumann, 1992; Wiesbuch et al.,
1990) do not distinguish between free and cell membrane-bound immunoglobu-
lins; however, it has shown that such assumption does not alter the main conclu-
sions of SGIN models.