Immunity system complexity: T cell differentiating enemies (Introduction)

by David Turell , Friday, May 20, 2022, 17:20 (709 days ago) @ David Turell

Ways to tell self from non-self:

https://www.sciencemagazinedigital.org/sciencemagazine/20_may_2022/MobilePagedArticle.a...

"An immune response involves a coordinated orchestra of antigenrecognizing cells (e.g., T cells) and signaling molecules to mount a specific response against a pathogen. Although systems immunology offers a growing list of molecular interactions that are involved in antigen-specific immune responses, an understanding of how a response is mediated by different antigen characteristics is still lacking.

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"Discriminating between an organism’s self-molecules and foreign (nonself ) antigens is the hallmark of adaptive immunity. To achieve such specificity, the current model of T cell development in the thymus proposes that cells with very high reactivity to self-molecules (strong agonists) should be negatively selected, those with no reactivity (nonagonists) should die from neglect, and those with moderate reactivity (weak agonists) should be positively selected and enter peripheral tissues. This classification has led to the concept of antigen quality as a predictor for the efficacy of adaptive immune responses.

"Antigen-specific immune responses are highly sensitive to even a small amount of foreign antigens. To achieve such a degree of sensitivity and specificity, T cells sense the level of immune activity in their environments (quorum sensing) through interactions with signaling molecules and use this collective information to gauge the severity of a threat associated with an antigen. As a result, a mechanistic model of antigen-specific immune responses could involve a large number of cellular and molecular interactions with feedback, which are at least partially unknown.

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"..antigen recognition by T cells goes beyond equilibrium binding and involves kinetic proofreading mechanisms, whereby two or more antigen recognition events are combined to assure the fidelity of a response (i.e., the interactions are kinetically proofread). This mechanism is particularly crucial because self-antigens are present at much higher concentrations than nonself antigens, and their dissociation time from TCRs is only a few seconds shorter than that of nonself antigens (i.e., they have comparable binding constants).

"The structure of the inferred latent representation reflects the amount of information encoded by biologically plausible immune profiles. Achar et al. found that the inferred latent representation can associate immune response profiles to six different classes of antigens, which goes beyond the three conventional antigen classes of strong agonists, weak agonists, and nonagonists. It remains to be seen how these six classes are related to the biologically meaningful molecular features of antigens." (my bold)

Comment: please read the above carefully. It describes how scientists are trying to fully understand T cell functions and find they can differentiate self from non-self in six levels. These are vital protections from infection. They must work properly or organisms will not survive. There is no way a trial and error approach will work. It can only appear i nits present form if it were totally designed, as is, from the beginning.