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All cells containing a nucleus present MHC-I, while some specialized cells present MHC-II in addition to that. Since erythrocytes lack any MHC why do natural killer cells not attack them?

It is my understanding that any cell which starts presenting foreign peptides on MHC-I will undergo apoptosis after Th finds them, or if they stop presenting anything at all, they will be eliminated by the NKs.

So what mechanism prevents erythrocytes from being destroyed by the immune system?

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  • $\begingroup$ Too bad the duplicate has an answer, such as it is, only in a comment under one of the three "Answers". $\endgroup$ – mgkrebbs Jul 15 at 6:08
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    $\begingroup$ I'm voting to reopen. The linked question is not a duplicate and doesn't have a suitable answer for this specific question. $\endgroup$ – iayork Jul 15 at 11:09
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The question states, not quite correctly, that "if they stop presenting anything at all, they will be eliminated by the NKs". In fact, simply not having MHC is not enough to trigger destruction by NK cells.

NKs have a two-part trigger. Part 1 is an activator; part 2 is a suppressor. When the activator is present, and the suppressor is not present, then NK cells will destroy the target.

The suppressor is typically MHC class I, which is present on almost all normal cells. That means that NK cells will not destroy normal cells. There are many different activators, but most normal cells have at least one of the activators also present. That means that NKs are normally primed to destroy, but refrain from destruction because they also sense the suppressor.

With that explanation, it should be clear why RBC are not destroyed by NK cells. Even though they lack the suppressor, they also lack any activators. Since there are no activating signals, the NKs don't need to be also suppressed, so the lack of MHC doesn't lead to an attack.

Sample references:

It's also possible that RBC further protect themselves by showing a "marker of self" on their surface (Role of CD47 as a Marker of Self on Red Blood Cells) but that doesn't change the important point about NKs mode of activation.

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