Moreover, the presence of multiple phosphorylation sites enhances the probability of bistable behavior of the system when tethered with scaffold proteins. The properties of a bistable switch have recently been investigated to conclude that the mechanism must be distributive to generate multiple steady states and that bistability is more likely with a large number of phosphorylation sites. The phenomenon of ultrasensitivity has also been reported to increase linearly with the number of phosphorylated sites. Phosphorylation plays a critical role in the regulation of the immune system. However, there is a clear gap in the mechanistic understanding of the role of multisite phosphorylation in this process. Phosphorylation governs protein signaling via Signal Transducers and Activators of Transcription proteins. The STAT proteins are critical for many fundamental cellular processes such as proliferation, differentiation, cell growth and survival. They operate in the ubiquitous JAK/STAT pathway. There are seven mammalian STAT proteins each with a specific role in the immune system. A considerable amount of experimental evidence shows that dysfunction in the JAK/STAT signalling mechanisms leads to inflammatory diseases. The STAT proteins are activated by phosphorylation of their C-terminal transactivation domain by Januse Kinases at Tyr701 for STAT1 in LY2109761 response to type II interferons and Tyr705 for STAT3 in response to Interleukin 6 or 10. Phosphorylation at Tyr705 leads to the dimerization and regulates the activation of STAT3. There are three classes of STAT negative regulators: Suppressors of Cytokine Signaling, Protein Inhibitors of Activated STATs and the simplest class Protein Tyrosine Phosphatases, for instance SHP-1, which reverses the activity of the JAKs. Interferon Regulatory Factor 5 is a latent transcription factor involved in autoimmunity. IRF-5 is known to contain six phosphorylation sites: Thr10, Ser158, Ser309, Ser317, Ser451 and Ser462, but only the last two have so far been shown to be functional. Several models for STAT3 and IRF-5 phosphorylation as part of larger models have been published recently. A classical approach for the phosphorylation of STAT3 by JAK has been employed in. Another report proposed sigmoidal Hill functions for phosphorylation of STAT3. An explicit mathematical model for IRF-5 phosphorylation is not currently available, but the phosphorylation of IRF-3 as part of the TLR4 pathway has been considered. The cells that differentiate in the thymus and are involved in cell mediated immunity are known as T cells. They circulate in the lymphoid organs and the blood in the form of naive T cells, which have not been in contact with antigens yet. After the interaction with the antigen the naive CD4+ T cells are activated and can differentiate into the specific T cell phenotypes, namely T helper 1, Th17 and regulatory T cells. Each of these phenotypes has its own function in the regulation of the immune response and a specific cytokine signature. Th1 and Th17 cells play a critical role in the regulation of the activity of the immune response and inflammation. Tregs are known for their antiinflammatory properties and for maintaining the immune tolerance. Th1 cells are defined by expressing IFN-c, Th17 cells by IL-17 and Tregs by IL-10. The specific phenotype is induced by the production of the specific cytokines. For example Th1 is induced by IL-12, Th17 by IL-6 and Tregs by TGF-b. These cytokines activate specific transcription factors, involved in the differentiation of the T cell subsets. Thus, the differentiation of T cells is a complicated process involving a complex scheme of regulation by cytokines and transcription factors.