Meta-Biol

• Pathways

The dual phosphorylated ITAMs recruit SYK kinase ZAP70 via their tandem SH2 domains (step 8). ZAP70 subsequently undergoes phosphorylation on multiple tyrosine residues for further activation. ZAP70 includes both positive and negative regulatory sites. Tyrosine 493 is a conserved regulatory site found within the activation loop of the kinase domain. This site has shown to be a positive regulatory site required for ZAP70 kinase activity and is phosphorylated by LCK (step 9). This phosphorylation contributes to the active conformation of the catalytic domain. Later ZAP70 undergoes trans-autophosphorylation at Y315 and Y319 (step 10). These sites appear to be positive regulatory sites. ZAP70 achieves its full activation after the trans-autophosphorylation. Activated ZAP70 along with LCK phosphorylates the multiple tyrosine residues in the adaptor protein LAT (step 11). PTPN22 can dephosphorylate and inhibit ZAP70 activity to downregulate TCR signaling (step 12).

Adaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with remarkable diversity tailored to recognize aspects of particular pathogens or antigens. During infection, dendritic cells (DC) which act as sentinels in the peripheral tissues recognize and pick up the pathogen in the form of antigenic determinants and then process these antigens and present them to T cells. These T cells of appropriate specificity respond to the antigen, and either kill the pathogen directly or secrete cytokines that will stimulate B lymphocyte response. B cells provide humoral immunity by secreting antibodies specific for the pathogen or antigen.

Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system.