Those few effective clones are enough for protection on re-exposure, even though most of the memory pool is irrelevant. The system ultimately relies on randomness plus early self-tolerance safeguards, not perfect tracking of clonal performance.

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#immunology
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#memory

By the time an antigenic challenge occurs, self vs non-self is already sorted out. The result is many clones, most of them useless, doing little yet still entering memory as “junk memory,” and a small minority that actually mattered in clearing the antigen.

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So how does the system function? Mostly through stochastic processes. Avoiding self-reactivity is handled earlier during thymic negative selection or Treg-mediated control at birth not during each new antigenic encounter.

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If a clone like A were actually recognizing self through cross-reactivity, giving it a self-amplifying loop would be dangerous. So strong positive or negative feedback mechanisms can’t safely guide clonal selection during the response itself.

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There’s also no positive feedback loop to selectively amplify the clones doing the real work. Why? Because the immune system also can’t know whether an effective clone like A is attacking foreign antigen or accidentally reacting to self.

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Once the antigen disappears, all the system knows is that something worked, but not who did it. Clone A can’t signal “I handled this,” and C might get equal credit without contributing. The negative feedback of antigen loss treats all clones the same.

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How would it know whether B and D are useful? And even among effectors A and C, how can the system tell whether A or C actually did the work? C might expand yet do nothing, while A clears the antigen. Mechanistically, the system has no way to know.

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Maybe A and C become effectors while B and D head straight into memory. But if A and C die after the antigen is cleared, and B and D become memory without ever proving themselves, doesn’t that create a problem for how the immune system evaluates clones?

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