T cell not because of its structure per se, but because its affinity allows it to bind the TCR for a lengthy enough time period, and the SAg mimics this temporal bonding. Low levels of Zap-70 have been found in T-cells activated by SAgs, indicating that the normal signaling pathway of T-cell activation is impaired. It is hypothesized that Fyn rather than Lck is activated by a tyrosine kinase, leading to the adaptive induction of anergy. Both the protein kinase C pathway and the protein tyrosine kinase pathways are activated, resulting in upregulating production of proinflammatory cytokines. This alternative signaling pathway impairs the calcium/calcineurin and Ras/MAPkinase pathways slightly, but allows for a focused inflammatory response. Direct effects SAg stimulation of antigen presenting cells and T-cells elicits a response that is mainly inflammatory, focused on the action of Th1 T-helper cells. Some of the major products are IL-1, IL-2, IL-6, TNF-α, gamma interferon (IFN-γ), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and monocyte chemoattractant protein 1 (MCP-1). This excessive uncoordinated release of cytokines, (especially TNF-α), overloads the body and results in rashes, fever, and can lead to multi-organ failure, coma and death. Deletion or anergy of activated T-cells follows infection. This results from production of IL-4 and IL-10 from prolonged exposure to the toxin. The IL-4 and IL-10 downregulate production of IFN-gamma, MHC Class II, and costimulatory molecules on the surface of APCs. These effects produce memory cells that are unresponsive to antigen stimulation. One mechanism by which this is possible involves cytokine-mediated suppression of T-cells. MHC crosslinking also activates a signaling pathway that suppresses hematopoiesis and upregulates Fas-mediated apoptosis. IFN-α is another product of prolonged SAg exposure. This cytokine is closely linked with induction of autoimmunity, and the autoimmune disease Kawasaki disease is known to be caused by SAg infection. SAg activation in T-cells leads to production of CD40 ligand which activates isotype switching in B cells to IgG and IgM and IgE. To summarize, the T-cells are stimulated and produce excess amounts of cytokine resulting in cytokine-mediated suppression of T-cells and deletion of the activated cells as the body returns to homeostasis. The toxic effects of the microbe and SAg also damage tissue and organ systems, a condition known as toxic shock syndrome. If the initial inflammation is survived, the host cells become anergic or are deleted, resulting in a severely compromised immune system. Superantigenicity independent (indirect) effects Apart from