Abstract
Here, we outline an overview of the mammalian immune system that updates and extends the classical clonal selection paradigm. Rather than focusing on strict self-not-self discrimination, we propose that the system orchestrates variable inflammatory responses that maintain the body and its symbiosis with the microbiome while eliminating the threat from pathogenic infectious agents and from tumors. The paper makes four points: The immune system classifies healthy and pathologic states of the body—including both self and foreign elements—by deploying individual lymphocytes as cellular computing machines; immune cells transform input signals from the body into an output of specific immune reactions.Rather than independent clonal responses, groups of individually activated immune-system cells co-react in lymphoid organs to make collective decisions through a type of self-organizing swarm intelligence or crowd wisdom.Collective choices by swarms of immune cells, like those of schools of fish, are modified by relatively small numbers of individual regulators responding to shifting conditions—such collective inflammatory responses are dynamically responsive.Self-reactive autoantibody and T-cell receptor (TCR) repertoires shared by healthy individuals function in a biological version of experience-based supervised machine learning. Immune system decisions are primed by formative experience with training sets of self-antigens encountered during lymphocyte development; these initially trained T cell and B cell repertoires form a Wellness Profile that then guides immune responses to test sets of antigens encountered later. This experience-based machine learning strategy is analogous to that deployed by supervised machine-learning algorithms.We propose experiments to test these ideas. This overview of the immune system bears clinical implications for monitoring wellness and for treating autoimmune disease, cancer, and allograft reactions.
Highlights
We outline an overview of the mammalian immune system that updates and extends the classical clonal selection paradigm
4) Self-reactive autoantibody and T-cell receptor (TCR) repertoires shared by healthy individuals function in a biological version of experience-based supervised machine learning
Immune system decisions are primed by formative experience with training sets of self-antigens encountered during lymphocyte development; these initially trained T cell and B cell repertoires form a Wellness Profile that guides immune responses to test sets of antigens encountered later
Summary
It was taught that the function of the immune system was to distinguish between the self and the foreign— whatever was foreign was to be rejected and, in contrast, what belonged to the self was to be ignored [1]. We need not bother to define the tricky terms self and foreign [2] because we know that the functions of the immune system are much more varied than a simple self-not-self binary distinction [3, 4]: The immune system clearly protects the body from invading pathogens, but it welcomes and manages our symbiosis with the essential bacterial microbiome and viral components of the body [5]; the immune system heals wounds and repairs injuries to maintain us in the face of the accidents of life [6, 7]; it detects and destroys aged cells and transformed tumor cells [8, 9]; and it rejects tissues transplanted from allogeneic individuals, while tolerating our foreign symbionts [10]. The inflammatory process itself can be the cause of disease— autoimmune diseases result from such misguided inflammatory processes
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