Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) - Volume 10, Issue 1, 2010

A bidirectional circuit exists between the neuroendocrine and immune systems that functions to maintain and protect the internal homeostasis of the organism. In this context, interactions between thyroid hormones (TH) and the immune system are revealed mainly by the presence of specific receptors for TH on lymphocytes or by the frequent immune alterations associated with physiological or pathological fluctuations of TH. In this context, both hypothyroidism in humans and experimentally-induced hypothyroidism in rodents have been shown to diminish thymus activity, to lead to spleen and lymph node involution and to depress humoral and cell-mediated immune responses. All these effects are reversed by restoration of the euthyroid state. In contrast, in vivo up-regulation of TH levels, but not those of thyrotropic hormones, leads to an increase in lymphocyte reactivity and an increment of inflammatory and T-cell derived cytokines. Additionally, TH direct actions on T lymphocytes were recently demonstrated as well, showing that TH are able to increase T cell proliferation through the activation of both nongenomic and genomic intracellular signals. These actions point to the important role that these hormones play in regulating lymphocyte function. Additional studies are needed of the mechanisms involved in cellular interactions within the immunoneuroendocrine network, as well as the consequences of their alterations. Such studies may disclose contributions of TH to the pathophysiology of the immune system and thus suggest novel approaches to modulation of immunopathology via manipulation of endogenous TH.

Pattern recognition receptors (PRRs) recognize and respond to evolutionarily conserved microbespecific molecular patterns and therefore play a critical role in host defense towards pathogenic organisms. The current dogma is that the expression and activation of PRRs in innate immune cells serve as an essential link between the innate and adaptive arms of immunity. This has been demonstrated in studies on PRRs, in particular the toll-like receptors (TLRs) and C-type lectins, which revealed that innate recognition of pathogens results not only in the expression of innate response genes, to control or eliminate infectious agents, but also in the expression of chemokines and cytokines that promote and shape the acquired immune reaction. Recent reports of TLR and other PRR expression and the presence of functional TLR pathways in B and T cell subpopulations indicate that PRR signaling could also induce or modulate adaptive immune responses directly, suggesting that cytokine production and survival/proliferation of activated B and T cells could be finely tuned in a pathogen-specific manner. This review analyzes the available evidence on the expression and possible functions of TLR and other PRRs in adaptive immune cells.

Background: Organ transplantation is a life saving procedure in patients with end-organ disease. While improvement in surgical techniques made transplantation possible in the 1960s, advances in immunosuppressive therapies have resulted in lower rates of acute cellular rejection and consequently, significant improvements in patient and graft survival after solid organ transplantation. Aim: To discuss all immunosuppressant medications in organ transplantation. These medications are potent, have substantial drug interactions, and have acute and chronic toxicities. Conclusion: Immunosuppressive protocols must be balanced not only to minimize graft rejection, but also to avoid complications related to adverse effects. Further studies are needed to optimize optimal use of these medications in relation with immune tolerance. This article provides a general overview of efficacies and toxicities of current immunosuppressive therapies.

Mosquito-borne flaviviruses are a group of viruses belonging to the genus flavivirus and the family flaviviridae. Dengue Virus, Yellow Fever Virus, Japanese Encephalitis Virus and West Nile Virus are some examples of the medically important flaviviruses. The disease manifestations of these flaviviruses range from the mild febrile fever to the life-threatening encephalitis and hemorrhagic manifestation. Mosquito-borne flaviviruses are human pathogens of increasing global importance as they become more prevalent due to changes in the world climate and globalization. Extensive research has been carried out to understand these viruses and to devise ways to effectively treat the diseases caused by these mosquito-borne flaviviruses. However, no effective anti-viral treatment for these flaviviruses is currently available. Many novel anti-viral immunotherapy approaches are now being undertaken to find ways to effectively counter these viruses. This review will outline the potential anti-viral immunotherapies that can be used to treat these mosquito-borne flavivirus infections. Various strategies used for the discovery of potentially therapeutic antibody against these flaviviruses will also be discussed.