Editing T helper cell (section)

===Survival (signal 2)===
Having received the first TCR/CD3 signal, the naïve T cell must activate a second independent biochemical pathway, known as Signal 2. This verification step is a protective measure to ensure that a T cell is responding to a foreign antigen. If this second signal is not present during initial antigen exposure, the T cell presumes that it is auto-reactive. This results in the cell becoming [[anergy|anergic]] (anergy is generated from the unprotected biochemical changes of Signal 1). Anergic cells will not respond to any antigen in the future, even if both signals are present later on. These cells are generally believed to circulate throughout the body with no value until they undergo [[apoptosis]].<ref>{{cite journal | vauthors = Elmore S | title = Apoptosis: a review of programmed cell death | journal = Toxicologic Pathology | volume = 35 | issue = 4 | pages = 495–516 | date = June 2007 | pmid = 17562483 | pmc = 2117903 | doi = 10.1080/01926230701320337 }}</ref>

The second signal involves an interaction between [[CD28]] on the CD4<sup>+</sup> T cell and the proteins [[CD80]] (B7.1) or [[CD86]] (B7.2) on the professional APCs. Both CD80 and CD86 activate the CD28 receptor. These proteins are also known as [[Co-stimulation|co-stimulatory molecules]].{{citation needed|date=August 2020}}

Although the verification stage is necessary for the activation of naïve helper T cells, the importance of this stage is best demonstrated during the similar activation mechanism of CD8<sup>+</sup> [[cytotoxic T cell]]s. As naïve CD8<sup>+</sup> T cells have no true bias towards foreign sources, these T cells must rely on the activation of CD28 for confirmation that they recognize a foreign antigen (as CD80/CD86 is only expressed by active APC's). CD28 plays an important role in decreasing the risk of T cell auto-immunity against host antigens.{{citation needed|date=August 2020}}

Once the naïve T cell has both pathways activated, the biochemical changes induced by Signal 1 are altered, allowing the cell to activate instead of undergoing anergy. The second signal is then obsolete; only the first signal is necessary for future activation. This is also true for memory T cells, which is one example of [[Adaptive immune system|learned immunity]]. Faster responses occur upon reinfection because memory T cells have already undergone confirmation and can produce effector cells much sooner.{{citation needed|date=August 2020}}