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The model I propose, in contrast, is conservative in that it embodies such a process of self—nonself discrimination. I believe this neglect undermines our ability to understand how the immune system functions. I wish to respond to these questions, to foster discussion, but I try not to be too elaborate, as this would render the few salient ideas I offer for consideration, less accessible. I have responded in two ways. Consider two CD4 T cells emigrating from the thymus, one specific for a peripheral self-antigen, pS, the other specific for a foreign antigen, F, in the circumstances where both are present. Selecting the item displayed will insert text that looks like this: The issue is whether PAMPs and danger are the critical elements in determining whether antigen activates or inactivates CD4 T cells, as proposed by Janeway and Matzinger 33 — Some self-antigens, typically and predominantly present in specialized organs, are not always present in primary lymphoid organs at the level required to reliably cause central tolerance. He pointed out how much of our knowledge, pertinent to the activation and inactivation of different lymphocyte types, was naturally accommodated by a Two Signal mechanism.
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