Dear Science,
Can I actually build immunity to iocaine powder, or a similar substance that isn't made up?
Battle of Wits
Yes, depending on the substance, but only to an extent. The body can deal with toxins and poisons in a few different ways, most of which can be amped up with lucky genetics or some training. Still, you shouldn't count on them to win a contest with a Sicilian when death is on the line.
Antibodies produced by the immune system can grab up the toxin; this is how the tetanus vaccine (among a few others) works, capturing the tetanus toxin before it can cause damage. The senses of smell and taste, particularly the bitterness receptors, are decent at detecting many poisons; barfing is your next line of defense—a plus for survival, but a loss on style points. Another neat trick is to eat something like activated charcoal, which will capture the poison in the gut.
If you don't barf, don't have protective antibodies against the poison, and don't have something else in your gut that'll absorb the toxin first, the gut will transfer it into the blood. Still, all is not lost. Almost all of the blood from the gut first goes to the liver before hitting the rest of the body. The liver lives for this moment. As the blood trickles through the organ, legions of enzymes tweak almost all of the molecules and proteins absorbed into the blood—including most toxins. The CYP450 family of proteins is the key to victory—the major enzymes that protect you against all manner of toxins. Past exposure to poison can increase the amount and activity of these enzymes; thus, this is a way you can gain protection from a poison through prior exposure.
Ever wonder how chronic alcoholics can drink that much? Why does the Pill stop working when you take certain antibiotics? By turning up or down CYP450 enzymes. Your liver treats most medications like poisons, processing them with the same enzymes. As the number of drugs has increased, so has the number of weird interactions through the liver. Mevastatin, a cholesterol-reducing drug, is safe—unless you happen to be eating red grapefruit while taking it. The grapefruit inhibits a key CYP450 enzyme used to clean up after the drug; without the enzyme, the mevastatin builds up and starts destroying your muscles. Bizarre. Drug interaction is one of the more artful ways a physician can kill you.
So, if you wish to become immune to a poison, start designing vaccines or playing with your liver. In theory, it might work. Science recommends neither activity. Fencing or feats of strength seem a wiser choice. 
Inconceivably Yours, Science
