Many of the more basic cells in the immune system just do their job without too much subtlety; run around, find bugs, kill them. Life is simple when you are a neutrophil.
The more sophisticated cells of the immune system like lymphocytes are under highly complex control, understandably so, because they can set off the alarm that sets a full-blown immune response into motion. After lymphocytes recognise another cell (“passport please”) their response to this recognition is influenced by dozens of further “handshakes”, a whole committee of checks and double-checks. These “checkpoints” have evolved to ensure that immune responses are always appropriate, and never occur without a good reason.
These checkpoints are pairs of proteins that line-up and face-off against each other when the surface of the lymphocyte and the surface of the cell it is interrogating are in contact. At the end of this arm-wrestle, a committee decision is made; either the lymphocyte turns on the alarm to set off an immune response, and tries to kill the cell in front of it, or the lymphocyte is satisfied that the other cell is not dangerous, allows it to pass, but most importantly allows all future identically identifying cells a “free pass”.
A few of the checkpoint proteins have become very important for the treatment of cancer (CTLA-4, PD-1 and PD-L1) and the remainder of them are being enthusiastically investigated to see if they too can be targeted to help people with cancer.