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This is a variation of the "does the immune system run out of memory" question.

Here's a (possibly imperfect) thought experiment: You take two twins. One of them lives in a bubble from birth. One of them is Mike Rowe from Dirty Jobs, and gets exposed to all sorts of antigens as well as vaccines. When they are 30 years old, you expose both of them to an antigen that neither has seen before. What happens?

PS: Note that while this example is illustrative, my question is really about whether there is any way at all in which the response of a naive immune system to a novel antigen is different from that of a very educated immune system (which has also not seen the antigen before). For instance, would the same amount of antigen be required to stimulate the immune system? Would the antibody count several months or years post-exposure differ?

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  • $\begingroup$ Of course, we've never done this experiment (bubble boy without an immune deficiency), but I'd speculate that the regulatory environment for the immune response would be quite different. It's hard to say whether the 30 year old immune virgin would react to exposure like an infant, or something different entirely, but you can't just consider the novel antigen and the immune cell that recognizes it. In vitro, in standardized conditions, you would expect a naive B or T cell from either brother to react to a novel antigen in the same way, but that's not what you're asking. $\endgroup$
    – De Novo
    Sep 21 '18 at 22:11
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They will both go through a primary and secondary immune response. So first low affinity antibodies will bind, the corresponding b cells will undergo affinity maturation, somatic hypermutation until high affinity (perfectly fitting) antibodies are available and these antibodies will finally undergo class switching.

Depending on the antigen an innate immune response will also be triggered as part of the first line of defense. There is no difference in the immune response between these two hypothetical brothers.

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  • $\begingroup$ While the initial response would be the same because neither person has corresponding antibodies, would there be a difference in the amount of time that it takes the killer T cells to respond and destroy the antigen? Bubble boy never uses his killer T cells and Mike Rowe would use them all the time. Would that make a difference in response time or the quantity of killer T cells? $\endgroup$
    – bvderp
    Apr 19 '14 at 19:38
  • $\begingroup$ Not when we assume that both have never seen this antigen. $\endgroup$
    – Chris ♦
    Apr 19 '14 at 19:39
  • $\begingroup$ I think this is the right answer, barring cross-reactivity. In other words, Brother Ed (educated) may have not have seen a specific new antigen, but he may have been educated with another antigen such that his antibodies cross-react with the new one. So, on balance, I'd err on the side that Ed might indeed react. Feel free to add if it helps. $\endgroup$
    – PlaysDice
    Apr 20 '14 at 14:32
  • $\begingroup$ This answer neglects the general changes that occur in immune cell and antibody populations resulting from 30 years of exposure to the environment. Cross reactivity is one issue. There are many others, e.g., the regulatory effect of the entire population of the gamma fraction of plasma, and changing populations of $T_{reg}$ and Th17 cells. The adult immune system is quite different from an infant's immune system, and much of this appears to be related to cumulative exposure to non-self antigens. It's not as simple as whether or not you've been exposed to a specific antigen. $\endgroup$
    – De Novo
    Sep 21 '18 at 22:00

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