“…The steady state level of primer eTh anti‐NS is homeostatically maintained low compared to that of the iTh anti‐NS; it is just sufficient to get the response of the system started. These aspects of the S–NS discrimination have been previously discussed in detail .…”
Section: Extracting the Default Or Core Principles For Each Module Ofmentioning
The immune system is an anticipatory mechanism designed by evolution to protect the individual against noxious agents and harmful cellular debris. In order to recognize substances that it has never encountered, the immune system somatically generates an appropriately sized random (with respect to self and nonself [NS]) recognitive repertoire that is coupled to a biodestructive and ridding output. Consequently, a Self-NS discrimination is required in order to avoid autoimmunity. This essay is an attempt to highlight the core principles upon which this anticipatory mechanism depends in order to function.
“…The steady state level of primer eTh anti‐NS is homeostatically maintained low compared to that of the iTh anti‐NS; it is just sufficient to get the response of the system started. These aspects of the S–NS discrimination have been previously discussed in detail .…”
Section: Extracting the Default Or Core Principles For Each Module Ofmentioning
The immune system is an anticipatory mechanism designed by evolution to protect the individual against noxious agents and harmful cellular debris. In order to recognize substances that it has never encountered, the immune system somatically generates an appropriately sized random (with respect to self and nonself [NS]) recognitive repertoire that is coupled to a biodestructive and ridding output. Consequently, a Self-NS discrimination is required in order to avoid autoimmunity. This essay is an attempt to highlight the core principles upon which this anticipatory mechanism depends in order to function.
“…Bretscher and Cohn kindly wrote letters supporting my promotion. I had begun webpages in 1998, and a personal note from Cohn declared that my immunology “website has been so useful to me that I hope you update and maintain it.” When discussing their further development of the 1968 Bretscher‐Cohn paper in Nature , Cohn wrote in 2012:A choice between two pathways upon encountering an antigen requires, as a matter of logic, two linked epitope‐specific signals. It was much later that we learned that Forsdyke (1968) in an elegant paper had at the same time also fingered the logic of the decision step as requiring two signals.…”
Distinctive “two signal” paths in immunology, taken by researchers with different academic backgrounds, seem to have both contained facets of the truth. Having been influenced by education at a medical school where Almroth Wright’s early contributions were not forgotten, the author’s “path less followed” led to views that began to gain recognition late in the twentieth century when the intimate relationship between innate and acquired immunity became more apparent.
“…(1) Express the somatically generated repertoire on a one cell-one paratope basis (haplotype exclusion); (2) Be devoid of effector function; (3) Have two pathways open to them, inactivation and activation. The evolutionary selection pressure for haplotype exclusion is 1) to optimize specificity and 2) to minimize the production of functionless TCR/BCR.…”
Section: The Views Of the Workhop Participantsmentioning
A summary of the workshop with its laudatory goal 'to reveal the foundational concepts in immunology' was recently published in SJI with an invitation to outsiders to comment. In the end, a foundational concept is one upon which we can all agree. This requires debate and meaningful experimentation. The goal of this commentary is to provide some of that. Most of immunology is description of an observation (i.e. a fact). However, what ties all the facts together as a discipline is theory or conceptualization that gives a general context to observation and predicts the next step. This is what is meant by 'foundational concepts'.
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