T helper cell
The first immunologic model was called the Self Non-self model and was suggested by Burnet and Frank Fenner in 1949, and refined over the years. It supposes that the immune system distinguishes between self, which is tolerated, and non-self, which is attacked and destroyed. According to this theory the chief cell of the immune system is the B lymphocyte, which is activated when it recognizes any non-self structure. Later it was discovered that in order to become activated, the B lymphocyte needs help from a CD4+ T helper cell, and that this T helper cell in turn also required a co-stimulatory signal from an antigen-presenting cell (APC) to be activated. The Self Non-self model developed according to these findings. Because APCs are not antigen-specific and are also capable of processing self structures, in 1989 Charles Janeway proposed a new theory, the so-called Infectious Non-self Model. It is based on the idea that APCs are activated via pattern recognition receptors (PRRs) which recognize evolutionary distant conserved patterns. These pathogen-associated molecular patterns (PAMPs) on such organisms as bacteria are recognized as infectious non-self, whereas PRRs are not activated by non-infectious self. However, none of these models can explain non-cytopathic virus infections, graft rejection or anti-tumor immunity.