Theoretical Models of Immune Processes - Immunological Computation: Theory and Applications - page 38

In DKP GC simulation model, there are three basic chambers (proliferation,
selection, and memory), each providing the excitatory and inhibitory (optional) layers
to allow nontrivial oscillatory dynamics in each GC subunit (Pramanik et al., 2002).
2.5 DangerTheory
h ere has been a long-standing debate among immunologists on the validity of
the classical self/nonself (SNS) discrimination theory (Bretscher and Cohn, 1970;
Hoff mann, 1975) and its importance in the detection and recognition processes.
Some alternative views have been proposed, such as the danger theory (DT)
(Matzinger, 1994), integrity model (Dembic, 2000), and the self-assertion model
(Varela and Coutinho, 1991).
h e self-assertion model considers the danger as a result of the interaction
between external stimulus and current state of the immune system; also, the
same stimulus can produce diff erent responses at diff erent times (Bersini, 2002).
According to this approach, the reaction to an antigen will depend on the system's
evolution, which also includes the history of all previous external stimuli; thereby,
it is assumed that an organism is in a sate of homeostasis—some metabolic equilib-
rium actively maintained by complex biological mechanisms that operate through
autonomous behavior to counterbalance disrupting changes. h is approach sug-
gests that more attention should be devoted to self-regulation mechanisms, which
allow the immune system to maintain a viable organization, despite the presence
of numerous diff erent dynamic elements with complex behaviors (Varela and
Coutinho, 1991).
h e DT (Matzinger, 1994), which is claimed to be a more realistic approach
compared to the classical SNS discrimination model ( Von Boehmer and Kisielow,
1990; Bretscher and Cohn, 1970; Hoff mann, 1975), is discussed next. In an SNS
discrimination model, the word “foreign” is used to mean “that to which the
immune system should respond,” whereas the term “self ” means “that to which the
immune system should be tolerant.” In DT model, the self is considered as harmless
elements to which the body develops tolerance, which may also include antigens
such as commensal organisms and parasites that do not cause any cellular damage.
Accordingly, the immune system becomes tolerant to antigens that are not neces-
sarily the same as self, which do not pose any danger (Figure 2.6).
In DT, the immune response is determined by the presence or absence of alarm
signals; some “danger signals” such as tissue damage triggers a myriad of immune
reactions and responses and APCs are activated by endogenous cellular alarm sig-
nals from distressed or injured cells.
According to Matzinger (1994), our bodies are never completely tolerant. As
long as the thymus and bone marrow are producing new B and T cells, there will
be a few new circulating self-reactive lymphocytes. h us, a question that arises
is “what stimulates these self-reactive cells and what maintains the response.”