Theoretical Models of Immune Processes - Immunological Computation: Theory and Applications - page 32

2.2.3 Third-Generation Immune Networks

As a result of criticizing SGIN models and questioning the assumption that T cell
help is never a limiting factor for B-lymphocyte proliferation or antibody produc-
tion, Stewart and Carneiro (1999) proposed an extended version of the model (pro-
posed by Varela et al., 1988), which is known as third generation INs (TGIN).
TGINs introduced the concepts of the central immune system (CIS) and periph-
eral immune system (PIS). h e CIS represents a group of activated, autoreactive, and
interconnected lymphocytes, which represents 10-15 percent of the total number of
lymphocytes. h e PIS contains the remaining 85-90 percent of all type of lympho-
cytes that are encountered in lymphoid organs (Stewart and Carnerio, 1999).
h e CIS is composed of a network of clones, which exhibits autonomous activ-
ity and integrates antigens into its ongoing regulatory dynamics. However, the PIS
is composed of lymphocyte clones, which remain in a resting state unless they are
specifi cally activated by an antigen resulting in immune response. h us, the PIS
only represents potential network targets for eventual recruitment through activa-
tion, in case this network space evolves to include them. h erefore, PIS takes care of
reactions with the immunizing antigens. In contrast, CIS deals with body antigens.
It is also assumed that resting lymphocytes are disconnected from regulatory infl u-
ence from the network, thus providing them ideal conditions to respond to external
antigens. h erefore, conventional antigens provide specifi c stimulation according
to Burnet's clonal selection theory (Burnet, 1959).
TGIN models incorporate B and T cell cooperation to accommodate both
structural and functional properties of CIS and PIS in a coherent way, and also
explain how the CIS and PIS distinction can emerge from the self-organizing
properties of the network. To defi ne the frontier between CIS and PIS, the TGIN
model (Stewart and Carneiro, 1999) assumed that any given lymphocyte clone
belongs either to the CIS or to the PIS at any given time; they showed distinc-
tion between the structure and function and exhibit cooperation between B and
T lymphocytes. New antibodies produced through antigenic experiences enter
the network and alter its organization, thus allowing the formation of a “sys-
temic memory.” However, expanded clones fi nd their internal legends in the net-
work structure for their long-term preservation, even in the absence of external
antigens.
In TGINs, the B cell activation is considered to occur in two steps:

• Induction . h e activation of lymphocytes based on the degree of stimula-
tion on a receptor by cross-linking agents such as anti-idiotypic circulating
antibodies or self-antigens. In this model, the induction is described by a
characteristic lognormal function, as in SGINs.
• Cooperation between an induced B cell and activated T cell . h is cooperation
leads to the “full” activation of the B cell. h us, a function that describes
the competition of B cells to get help from T cells is defi ned as a function of