As B cells require eTh cells to enter Module 3, MAPK inhibitor one can extrapolate to the T-cell level and reasonably begin construction of the composition of each effector ecosystem. The crucial aspect of this experiment is that a finding that switching of the unexpressed chromosome is random would rule out a Trauma Model. This after all is the test of a successful theory. There exists a family of peripheral S-components that is ectopically expressed in

thymus under the control of the transcription factor, Aire. In an Aire-defective mouse mutant at about 3 weeks after birth, a humoral autoimmune attack on these peripheral S-components is initiated. The question then is, What is the relationship between the Ig-isotype used for the autoimmune attack and a particular S-component? Appropriate ectopic expression in foetal thymus of a delayed expression peripheral S-component would permit negative PS-341 molecular weight selection of the iTh anti-that-S and the establishment of tolerance to it long before it is expressed as a physiological entity peripherally. The mature or responsive immune system treats

every de novo presented antigen, whether it be S or NS, as an NS-component. The autoimmune response to peripheral self in Aire-negative mice is presumably due to delayed expression S-components [49], which in these mutant mice are treated as NS. The experiment then is to isolate B-cell hybridomas from Aire-negative mice at various times after birth, select those that are specific to identified cell-surface components and determine the isotypes of their secreted antibodies. Under find more the Trauma Model, the prediction would be that all of the monoclonals mediating autoimmunity to distinctly different self-components would express the same Ig-isotypes. Initially or if no trauma signal

is involved, then they would all be IgM; if a trauma signal is involved that is the same for all self-components, then the switch would be to a given Ig-isotype. If each self-target induces a different Ig-isotype, then different trauma signals are involved and the immune system must chose its optimal ridding ecosystem dependent on the tissue attacked, not on any property of a pathogen–tissue interaction. This would be a striking result predicted by the Alarm Model as it implies that all pathogens interacting with a given tissue are ridded by the same effector ecosystem. ‘Independence’ in this case would be defined solely by the tissue, not the pathogen–tissue interaction. A self-component is not expected to trigger trauma signals. This expectation should obtain even if the self-component were treated as NS and placed under autoimmune attack.