Like its predecessor, Left 4 Dead 2 is set shortly after a worldwide pandemic of an infectious disease that rapidly transforms humans into zombie-like creatures and mutated forms that demonstrate extreme aggression towards non-infected (much like the ones in 28 Days Later). Few humans are immune to the disease, still carrying the infection but showing no symptoms.
The Source engine is a smooth experience at these settings, although we would notice some slight hitching from time to time.