(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
Way back in Blog #9, we referenced the Idiotype-anti-idiotype Regulatory Circuit (or Loop) and postponed its full discussion because of its complexity and more so, its relevance to cancer therapy. Now we’ll take our best shot at describing this “Idiotype-anti-idiotype Regulatory Circuit (or Loop)” with the goal of “…making it as simple as possible, but not simpler” (Einstein). So, here goes.
This complex theory starts with part of an antibody (an “arm” of the “Y” shape of antibodies) binding with a specific antigen. (easy so far.) Generated B cells begin to produce genetically cloned antibodies with unique profiles of epitopes or idiotypes (surface receptors). These are antigen binding sites for the cloned antibodies. These idiotypes increase their immunogenic stimulation through chemical bioregulators. These cloned antibodies begin producing an abundance of (cloned) B-idiotype cells. These B-idiotype cells generate the set of epitopes (proteins that determine antigenicity) on the "V” region (of the “Y”) of additional antibody molecules. (The “easy part” didn’t last too long, did it?) This stimulation induces anti-idiotype and anti-anti-idiotype antibodies (called antibody-2, antibody-3, and beyond) ultimately suppressing continued immune stimulation by binding with compatible Ts (T suppressor cells). This binding produces a regulatory closed-loop suppressor system (or circuit). It provides a continuing supply of antibodies that can eliminate a persistent antigen, like the carcinogen or carcinogenic stimulus in the case of cancer (Fig. 6.2). These anti-idiotype antibodies have the potential to provide long-lasting immunity, like a vaccine for cancer and for COVID-19. And that’s the big takeaway!
This “Idiotype-anti-idiotype Regulatory Circuit (or Loop),” also referred to as the “idiotype network theory (INT)” was discovered and described by a Danish immunologist, N.K. Jerne, who was awarded the Nobel Prize for medicine in 1984 for his work. But, between you and me, many scientists (myself included) still don’t fully understand what it all means (I told you it was complex!). But its potential benefits in therapies for autoimmune disease (e.g., multiple sclerosis, myasthenia gravis) as well as cancers and COVID-19 vaccine development, to our public health and humanity definitely earns it a place in this discussion. Imagine, a vaccine for cancer? You’ve gotta wonder what the “anti-vac luddites” will say about that. By the way, if you have been following the Figures through the many blogs, you may have noticed an evolving diagram starting back in Blog #5 with progressive figures (1.2, 1.4, 1.5, 1.6, 2.1, 2.2, 2.3, 5.1 and finally, 6.2 here) completing the full immune system flow diagram described throughout the text. These diagrams represent the evolution of the human immune response from innate immunity to its completion as response resolution, chronic inflammation or autoimmunity. Quite a biomedical journey, and we're not quite finished.
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