Targeted control for IS implies that in transplantations it may be better to block signal II instead of signal I. Several immunologists have reached this conclusion some years ago.
IS dynamics is called extremal dynamics (clones which are activated live longer while other clones die of neglect). It is known [6
] that such dynamics lead to an explanation for the long memory of IS without Ag persistence since this dynamics lead to the following relation: The probability of removal of a clone which has lived for time t is proportional to 1/(t+c) where c is a positive constant.
Integrated approaches for treatments imply that immunotherapy of cancer needs to be augmented by other treatment method. Also multi-drugs with independent modes of action should be used.
IS is a multi-functional multi-pathway system hence total failure of IS is rare.
In vivo experiments are significantly more reliable than in vitro ones to understand IS.
IS indicates some interesting topics mathematically e.g. decentralized systems, fractional order mathematics and extremal optimization etc.. Hence studying IS is quite interesting medically, biologically, physically, chemically, for computer scientists and even mathematically. The problem of protecting the data which faces computer scientists is almost identical to the one which IS has succeeded to solve. One expects that different approaches to the study of IS will be useful.
There is an extraordinary similarity between IS and insect swarms. Some of the principles of insect collective behavior includes [8
]: Non-selfish key individuals, positive and negative feed back, diversity and threshold responses. All
these characteristics exist in IS e.g. Th cells, high and low zone tolerance and the fact that most immune effectors have more than one function and almost all immune functions are done by more than one effector hence diversity is intrinsic in IS.
Some open questions
IS initiation is an important problem. Presently two theorems are proposed self-nonself and danger theory [9
]. Danger theory solves some problems in self-nonself theory e.g. lactation, pregnancy but is the correct theory one of them or a hybrid of them?
If danger is the only mechanism for IS initiation then what is the difference between autoimmunity and hypersensitivity? After all both are pathogenic immune responses to, normally, tolerated substances and cells.
The rejection of the second pregnancy due to Rh differences between fetus and mother, one thinks, poses a serious problem to self-nonself theory. But why the second pregnancy and not the first one is rejected. An answer is proposed that the danger signals result from the first child "birth". But one thinks that in this case the way of the birth (whether normal or cesarean) is expected to affect the duration of the second pregnancy before it fails (normal first birth gives a longer duration for the second pregnancy duration). Does agree or disagree with observation?
In anaphylaxes two mechanisms seem to be broken, the first is tolerance and the second is the control mechanism of the immune response. The immune response in the case of anaphylaxes may cause death!! The simultaneous breakdown of two mechanisms seems quite puzzling.
It is important to understand that what is proposed here does not replace the traditional approach to IS. It is proposed that few minutes spent on the design principles of IS may be helpful in trying to understand the huge amount of details that exists in IS.