How does the immune system tell self from non-self?

The innate discrimination between self and nonself primarily relies on receptors that identify molecules unique to pathogens, distinguishing them from those found in the host's own cells. This distinction is made possible by the presence of antigens on the surface of all cells. These receptors are encoded in the organism's germline, meaning they are inherited and do not change during an individual's lifetime. Nonself antigens are vital molecules for the survival and virulence of pathogens. They are often conserved within entire groups or families of microbes. When microorganisms invade the body their surface antigens are recognized as foreign, enabling the immune system to begin a response against them. 

There are also crucial self-identification molecules in humans, known as human leukocyte antigens.  These molecules are called antigens because they can trigger an immune response if transplanted into another person, such as during a skin graft. Each individual has a specific combination of HLAs, which their immune system typically recognizes as self. When cells with surface molecules differing from those on the body's own cells are identified as foreign, the immune system mounts an attack against them. These cells include cells modified by cancer, cells infected by the harmful microorganisms, or transplanted tissue cells.