Advances in Neuroimmune Biology

Several authors professed in favor of an autonomous Immune System, which is capable of defending the host. This argument is debated here at length. The existence of the Neuroimmune Supersystem, where immune participation is obligatory, mitigate autonomy. Also, the immune system is involved in physiology: it regulates reproduction, menstrual cycle, neonatal development, brain development and function, exerts neuroprotection, sleep, pain, stress, ageing, and glucose homeostasis are all regulated by immune mechanisms. Recently it has been proposed that gut microbiota affects brain function. Abnormal microbes led to disease, when normal bacteria were given, the disease subsided. What is the meaning of this observation? Would the brain notice the bacteria in the gut? Yes indeed, brain cells and the associated nerves express toll-like receptors (TLR) and for this reason will directly sense intestinal bacteria. We do not know what are the consequences of such sensations? The immune system is also stimulated by gut bacteria. The immune system owes its existence to this stimulus. Would the immune system communicate this event to the brain? Most certainly! Finally mucosal epithelial cells, which represent an army of effector cells, also express TLR. These mucosal cells have tremendous value in host defense. They become activated, defend, and produce cytokines and chemokines, through which they communicate with the entire Neuroimmune Supersytem. We conclude that the entire Neuroimmune Supesystem is involved in the regulation of intestinal microbes. This is most powerful and very effective regulation indeed.

Pituitary hormones have a large number of functions such as the regulation of stress response, electrolytic balance and reproduction. These include prolactin, growth hormone, oxytocin, vasopressin and ACTH, among others. Their synthesis and function depends on signals, constituted by the binding of the same hormones to specific receptors and induce or inhibit their synthesis or secretion. However, this is not the only regulatory mechanism of the pituitary hormone pathway. It has been observed that the neuroendocrine axes also interact with the immune system. This multi-directional communication between these systems has currently been accepted: pituitary hormones can regulate the functions of the immune system, and molecules secreted by the immune system modulate pituitary hormone function. This is the case of cytokines, which are secreted by different immunological cells and regulate their function. These molecules play a key role in the regulation by direct or indirect communication between the immunological and neuroendocrine systems and their production is influenced by the direct action of pituitary hormones and neurohormones on immune system cells. The action of some of the main pituitary hormones on the immunological system is summarized in this review.

Adaptive immunity plays a crucial role of protection of our body from pathogens while its deregulation leads to allergy and autoimmunity. T cells represent a major branch of lymphocytes, which are responsible for adaptive immunity, which represent a major pathway of immune function, which depend on their T-cell regulation. Cytokines also contribute to regulation. Over the past two decades, epigenetic mechanisms have been increasingly recognized to play a fundamental role in the proper execution of genetic programs that regulate immune function. The role of epigenetics in T-cell development and function (collectively called T-cell biology here) has been intensively studied, and epigenetic machinery is emerging as a potential therapeutic target to cure allergy and autoimmunity or to enhance immune response and immunological memory. In this article, the current findings and progresses of epigenetic study in T-cell biology are reviewed, focusing on genetic studies of so called epigenetic “writers” and “erasers” that catalyze addition and removal of covalent DNA and histone modifications.

Background/Aim: There is growing interest in the possible role of orexin in pathophysiological processes of multiple sclerosis (MS) for these patients frequently complain of fatigue and sleep disturbances and orexin is a neuropeptide known to play the crucial role in sleep/wakefulness regulation as well as in many other physiological functions. The present study was aimed to investigate morpho-functional characteristics of hypothalamic orexin system during adoptive transfer experimental autoimmune encephalomyelitis (atEAE). Method: Immunohistochemical detection of orexin-containing neurons was carried out on frontal brain sections of intact and atEAE Lewis rats. Quantity and relative transmission density (RTD) of orexin-positive neurons were assessed in definite hypothalamic structures on different brain levels (Swanson's atlas). Preproorexin gene expression in hypothalamic cells was assessed by qPCR. Results: Though the total quantity of orexin-positive cells was decreased in atEAE animals, differential quantification of these neurons revealed discreteness of hypothalamic zones response. Three possible variants can be distinguished: reduction of orexin-positive neurons quantity without any changes in their RTD (DMHa, LHAd, LHAvm); increase of RTD with no alterations in the quantity (more medial hypothalamic structures); both quantity reduction and RTD increment (more lateral hypothalamic structures). The preproorexin gene expression in hypothalamic cells of atEAE animals was slightly increased, that evidence the possible raise of orexin synthesis. Conclusion: atEAE induction causes alterations in balance between processes of orexin synthesis and utilization with the predomination of the latter. Hypothalamic orexinergic system participates in central mechanisms of CNS response to atEAE induction that could be important for understanding the pathogenetic processes during multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE) is a T cell autoimmune inflammatory disease of the central nervous system (CNS) that is a widely used animal model for the human demyelinating disease, multiple sclerosis. Bacterial melanin has proved to be a potent neuroprotector. It supports regeneration and motor recovery after CNS lesions. It is established that bacterial melanin can induce suppression of inflammatory process. Studies have revealed the negative correlation between skin pigmentation, vitamin D and the prevalence of autoimmune disease. Therefore we analyzed the anti-inflammatory effects of bacterial melanin in a rat EAE model. EAE was induced in adult albino male rats by immunizing with a rat spinal cord encephalitogenic emulsion. The development of EAE and neurological signs were evaluated by a standard protocol. Walking track analysis was conducted to evaluate motor recovery. Histomorphological analysis was applied to show cell infiltration into the spinal cord and effects of BM on the EAE pathomorphology. Pretreatment of EAE rats with bacterial melanin inhibited the development of disease, providing significant protective effect compared to control rats. BM treated rats showed lower degree of neurological deficit and higher level of motor recovery than controls. In treated rats histomorphological analysis demonstrated that brain infiltration with mononuclears was less expressed in bacterial melanin treated rats. Results show that bacterial melanin has protective effects in EAE and ameliorates symptoms of EAE.

Epigenetic regulation of gene expression is important for normal biological processes like immune cell development, immune responses, and differentiation from hematopoietic stem cells. Furthermore, it is well understood that epigenetic mechanisms can include methylation, histone modification, and more recently, microRNAs. Interestingly, aberrant epigenetic modification can also promote pathology in many diseases like cancer. The effects of methylation on gene expression and its resulting phenotype have been extensively studied. In this review, we discuss the inhibition of innate immunity that occurs in humans and animal models post-stem cell transplant. In addition, we highlight the changes methylation and microRNA profiles have on regulating pulmonary innate immune responses in the context of hematopoietic stem cell transplantation in experimental animal models.