Advances in Neuroimmune Biology - Volume 3, issue 3-4

Authors: Berczi, Istvan

Article Type: Research Article

Abstract: Adaptive immune reactions are based on lymphocyte proliferation, and are regulated by mechanisms which are involved in growth regulation of all cells in higher animals. Growth and lactogenic hormones (GLH) or type I cytokines (TICTK) are of fundamental importance for the development and function of the immune system and indeed for the entire organism. GLH/TICTK deliver the competence signal first to lymphocytes and other cells, which enable the cells to receive stromal or adherence signals that decide what the cell will do next, proliferate, differentiate, or function. This group of signals control cell growth, is delivered by cell-to-cell and cell-to-matrix …signalling. Adhesion molecules, tissue bound hormones, cytokines and matrix components mediate these signals. The antigen receptor belongs to the Immunoglobulin Family of adhesion molecules. Hence the antigen signal is capable to activate specifically the immune response, it can inhibit it also. Within the immune system antigen presentation represents the adhesion signal for which cell-to-cell interaction by adhesion molecules is obligatory. Adhesion molecules are fundamental to the organization of multi-cellular organisms and the signals delivered by them serve the basis of species, organ and tissue specific recognition. This recognition system has been perfected during evolution from self-recognition to individually specific antigen recognition. This system also plays a role in the elimination of degenerated and neoplastic cells. Cell-to-cell signaling has a dominant power over other signals to commit the cell to proliferation. The mitotic cycle is then completed by cytokine signals. Cytokines are tissue hormones which are usually, but not always, secreted by the same cells that deliver the second signal. IGF-I and insulin fulfil frequently this role, but cytokines may also deliver this third signal. The nature and combination of these three groups of signals will determine the fate of each cell, which may be survival, proliferation, differentiation and function or alternately apoptosis. Hormones and neurotransmitters, that alter signal delivery, modulate further this basic pattern of animal cell growth. It is concluded that GLH/TICTK maintain immunocompetence, which enables the immune system to respond to specific antigenic and mitogenic stimuli. Competence signalling comes from either the CNS or by TICTK, which is an autologous signal by the immune system. This dual signalling secures that the immune system is capable of surviving major disasters in the personal history of the host. Indeed memory T and B ells survive autonomously, and live trough major catastrophic events, and when the disaster is over, memory cells regenerate the adaptive immune system and bring back homeostasis of immune function which is the prerequisite for healing and homeostasis of the entire organism. The hypothalamic hormone, vasopressin (VP) regulates healing and recovery from disease. Show more

Keywords: Immunocompetence, growth hormone, polactin, adrenocorticotropic hormone, vasopressin, adaptive immune system, innate immune system, type I cytokines, competence signals, progression signals, cytokine signals, healing

DOI: 10.3233/NIB-012910

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 301-312, 2012

Authors: Berczi, Istvan | Quintanar-Stephano, Andres | Kovacs, Kalman

Article Type: Research Article

Abstract: Corticotropin releasing hormone (CRH) and Vasopressin (VP) are the hypothalamic immunoregulators. The CRH – adrenocorticotropic hormone (ACTH) - glucocorticoid (GC) and catecholamine (CAT) axis, jointly with Vasopressin (VP), stimulate innate immunity (INIM). During acute illness CRH activates the HPA-GC-CAT axis and INIM will be amplified up to 1000 times in 24–48 hours. GC and CAT stimulate directly INIM and also generate suppressor/regulatory T cells (Ts/r) which inhibit adaptive immune (ADIM) function. APR is a complex metabolic, endocrine and immune response which leads to a systemic inflammatory response. This is the last attempt to save the host organism from life threatening …disease/injury. In most cases healing and recovery will follow, so APR is a very effective in host defense. Show more

Keywords: Corticotropin releasing hormone (CRH), vasopressin (VP), adrenocorticotropic hormone (ACTH), cathecolamines (CAT), innate immunity (INIM), adaptive immunity (ADIM), acute phase response (APR), suppressor/regulatory T cells (Ts/r)

DOI: 10.3233/NIB-012909

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 313-328, 2012

Authors: Berczi, Istvan | Quintanar, Andres | Campos, Rafael | Kovacs, Kalman

Article Type: Research Article

Abstract: Vasopressin has emerged in recent years as a very important immunoregulatory peptide of the hypothalamus. Vasopressin is capable of maintaining immune function, both innate and adaptive immunity. This is due to the ability of vasopressin to stimulate both the hypothalamus-pituitary-adrenal axis and also prolactin. The hypothalamus-pituitary-adrenal axis is important for innate immune function, whereas prolactin and growth hormone maintain adaptive immunocompetence. Recent results show that vasopressin also has a direct regulatory effect on cytokines. During acute illness vasopressin will rise along with corticotrophin releasing hormone. In this case corticotrophin releasing hormone regulates the inflammatory process, and vasopressin supports this role. …Innate immunity is amplified by glucoicorticoids and catecholamines whereas adaptive immune function is suppressed. During chronic inflammation corticotrophin releasing hormone is repressed and vasopressin becomes the primary hypothalamic immunoregulator. Vasopressin gradually restores homeostasis by maitaining both the hypothalamus-pituitary-adrenal axis and prolactin secretion in balance and hence restores normal immune function and leads to healing and recovery of the organism. Therefore, the two hypothalamic immunoregulatory peptides, corticotrophin releasing hormone and vasopressin have different functions. Corticotrophin releasing hormone plays an important function in acute phase response, whereas vasopressin supports the acute phase response, but it is really the hypothalamic regulator of healing and of physiological immune regulation. Both corticotrophin releasing hormone and vasopressin exert numerous regulatory functions throughout the entire organism. It is beyond the scope of this review to present non-immune effects of these mediators. The first papers on oxytocin and growth hormone release go back to 1969–70. Little was done until recent times. It is now clear that oxytocin is an immunoregulatory hormone and it shows therapeutic value in the inhibition of septic conditions. This must be related of its immunoregulatory power. Oxytocin interacts with cytokines. So far oxytocin receptors were shown only on bovine T cells. The thymus and the pituitary gland produce oxytocin. Oxytocin injections to animals either stimulate (low dose) or inhibit (high dose) growth hormone secretion. Other evidence also supports the regulation of growth hormone by oxytocin. Oxytocin activates the adrenal corticotropic hormone axis in rats. Oxytocin will be released in response to sepsis, and other form of infections, inflammatory disease and in stress situations. On this basis we conclude that oxytocin is an immunoregulatory hormone and it participates in the acute phase response, it releases growth hormone, and activates the adrenal corticotropic hormone axis in rats. More work is required to appreciate fully the value of oxytocin in immune function. Show more

Keywords: Hypothalamus-pituitary-adrenal axis, innate immunity, prolactin, growth hormone, adaptive immunity, vasopessin, cytokines, acute phase response, oxytocin is immunoregulatory and active in acute phase reactions

DOI: 10.3233/NIB-012908

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 329-343, 2012

Authors: Santos-Argumedo, Leopoldo

Article Type: Research Article

Abstract: Natural antibodies are those antibodies present in the circulation of vertebrates that have not been previously exposed to specific antigens [1]. Natural antibodies were identified at the beginning of 20th century in the sera of humans or laboratory animals that had not been specifically immunized [1]. The best characterized and studied natural antibodies are those directed against blood group substances; it was reported that individuals with “0” blood group/type had sera/plasma antibodies against A and B antigens, whereas individuals of A group only have anti- B antibodies and vice versa [2, 3]. This puzzling observation was difficult to explain because …it was not known that blood group substances contain epitopes shared with microorganisms living in the gut of the individuals. Another observation was related to the relative “tolerance” of the individuals to their own blood group antigens because, at that time, no auto-antibodies were detected under normal circumstances. Using more sensitive methods it has been established that natural antibodies are present in the sera/plasma of normal healthy individuals and that these antibodies may have a physiological role connecting the immune system and may participate in the removal of aging cells, miss folded proteins, etc. [3–8]. Some characteristics of natural antibodies have been described over the years. Most natural antibodies are the IgM isotype, although other isotypes, such as IgG and IgA, are also present. Natural antibodies are germ line encoded, meaning that under normal circumstances they do not contain mutations in their variable regions. Natural antibodies have polyreactive binding sites, which imply that these antibodies may bind different epitopes with different structure/conformation. Due to their polyreactivity, natural antibodies often bind with low to medium affinity (105 –107 M−1 ) [4, 5, 9, 10]. As mentioned above, the specificity of these antibodies is directed against normal microbiota, but some clearly recognize self-antigens. Natural antibodies may also have a role in protection against invading microorganisms [7, 8, 11–15]. Show more

Keywords: B1 cells, natural antibodies

DOI: 10.3233/NIB-012912

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 345-352, 2012

Authors: Rybakina, E.G. | Shanin, S.N. | Fomicheva, E.E. | Dmitrienko, E.V. | Filatenkova, T.A. | Korneva, E.A.

Article Type: Research Article

Abstract: The authors analyzed the effects of short synthetic peptides and native DNA preparations on the function of the immune and neuroendocrine systems under various stress conditions. These preparations of peptides and nucleotides are known to be effective modulators of the immune and neuroendocrine systems. Here we discuss a new concept, which suggests that endogenous short peptides and their synthetic analogs bind to specific sequences of nucleotides in DNA strands. These site-specific peptide-DNA interactions modulate cellular genetic functions and form the basis of molecular-genetics of stress-protective short synthetic peptides. Protective action of nucleotide preparations on impaired functions of the immune and …neuroendocrine systems was shown. It seems that these effects are based on the ability of nucleotides to penetrate cells and subsequently splitting into nucleotides, which, after releasing from the cell, bind to purinergic P2 receptors. The results indicate that short synthetic peptides and native DNA preparations are capable of correcting stress induced impairment of neuroimmune function. Show more

Keywords: Stress, immune system, short synthetic peptides, nucleotides

DOI: 10.3233/NIB-012902

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 353-360, 2012

Authors: Fukuda, Sanae | Kuratsune, Hirohiko | Kajimoto, Osami | Watanabe, Yasuyoshi

Article Type: Research Article

Abstract: Chronic fatigue syndrome (CFS) is a disorder diagnosed following at least 6 months of disabling, unexplained mental and physical fatigue accompanied by other physical and psychological symptoms. Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology characterized by diffuse pain and tender points, which must be present for more than 3 months. These patients have the path similarity in psycho-neuro-endocrino-immunological system. In this paper, we introduce quantitative methods for assessment of fatigue developed by us. We then briefly summarize abnormalities found in CFS and FM, and show the neural and molecular mechanisms and introduce potential common biomarkers for CFS …and FM. Show more

Keywords: Chronic fatigue syndrome, fibromyalgia, psycho-neuro-endocrino-immunological system, fatigue-related problem scale

DOI: 10.3233/NIB-012906

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 361-366, 2012

Authors: Pukhalsky, Alexander | Shmarina, Galina | Alioshkin, Vladimir

Article Type: Research Article

Abstract: The brain and immune system being the two principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain, which is separated from the rest of the body by blood-brain-barrier (BBB), produces the cytokines by itself and the latter along with other neurotransmitters regulate various brain functions including cognition, memory, and neuronal differentiation. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain …where they begin to perform new functions. Long-term stress as well as physiological aging result in hormonal disturbance, first of all in the form of HPA axis depletion and dehydroepiandrosterone (DHEA) decrease. Thus, the changes observed in stressed subject form a picture typical of the aging brain. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. Clinical and experimental studies confirm efficiency of such choice although in some instances we can say only about indirect evidences. Show more

Keywords: Stress, cognitive dysfunction, HPA axis, glucocorticoids, dehydroepiandrosterone, cytokines, Tregs, inflammation, cyclophosphamide, macrolides, angiotensin II receptor blockers

DOI: 10.3233/NIB-012913

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 367-379, 2012

Authors: Berczi, Istvan | Quintanar Stephano, Andres | Nagy, Gyorgy

Article Type: Other

DOI: 10.3233/NIB-012919

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 381-386, 2012

Article Type: Other

Citation: Advances in Neuroimmune Biology, vol. 3, no. 3-4, pp. 387-388, 2012