If we consider an insecticide coming into contact with an insect, it is easy to see where resistance may occur. Firstly, the insecticide has to enter the insect. If the insecticide is systemic i.e. taken up by the crop, this will be by ingestion. If the insecticide is a contact insecticide, it will enter the body by crossing the cuticular wall. So here we have the first possible mechanism, penetration. A modification of the cuticle such that the entry of the insecticide is decreased. This mechanism does not confer high resistance, but is often found in combination with other mechanisms.
After crossing the cuticle, the insecticide has to travel to its target, usually part of the nervous system. During this journey, the insecticide may undergo detoxification by metabolic enzymes present in the insects. These enzymes are present to detoxify xenibiotics that the insects will ingest normally in feeding. This is the second mechanism of resistance, metabolic, occurring when these detoxification enzymes are either modified or more abundant.
Finally, the insecticide reaches its target and binds to the protein. This is the third and final mechanism, target-site resistance. This resistance is the result of a mutation of the protein resulting in a loss of binding affinity.