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In the antibody-mediated immune response, when the helper T cell gets activated by the costimulus (IL-2 and TNF-α secreted by the APC) which in turn produces IL-2, IL-2 acts in an autocrine manner. I'm just wondering why does IL-2 have to be secreted? Why doesn't it just exert an affect while it's already inside the helper T cell? What's the point of autocrine signalling?

I hope the answer isn't going to be, "Well, that's just the way it is..." because paracrine and endocrine make sense and have advantages, but autocrine just seems a bit extra.

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Why doesn't it just exert an affect while it's already inside the helper T cell?

Because it interacts with membrane-bound receptors. Those are outside so there is no way IL-2 (or any autocrine factor) could signal while inside the cell. It has to exit.

Now, the next question is why the receptor is membrane-bound and outside. As far as I understand there are two parts to this answer:

  1. Receptors are evolutionarily related so they follow similar synthesis pathways.
  2. Membrane-bound receptors are (all?) transcribed while being secreted into the endoplasmic reticulum. This causes their agent-binding portion to reside inside the ER. From there, vesicles bud off, are transported towards the cell membrane, merge with it, and hence the formerly inside portion of the protein ends up on the outside.
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paracrine and endocrine make sense and have advantages, but autocrine just seems a bit extra.

Autocrine also have advantages compared to internal signaling. Even if when you study mechanisms you think at single cells, cells are never alone in the body. If the message (IL-2) would be internal, each cell will individually respond according to its internal signaling levels. With the 'extra' to secrete the message, and having it sensed at the exterior (the receptor is membrane-bound), all the cells in the nearby are going to contribute to the average signal and will respond with average magnitude. It's a form of communication between a single cell population that does not affect other cells populations (the ones that does not express the IL-2 receptor).

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