Neuroimmunology: is the immune system a sense organ?

Through antigenic recognition, the immune system (SI) perceives an external information which is not directly perceptible by the central nervous system (SNC). So, two roles can be assigned SI: immuno-surveillance and information. Since 1980, it was proved that activated lymphocytes and others elements involved in the expression of immune response are able to secrete hormones, neuromediators and peculiar secretions. Moreover, the immune elements possess receptors for SNC secretions. A direct relations between lymphocytes, hypothalamus, hypophysis and endocrine glands has been suggested with implications in the understanding of some mental diseases and conditioning of the immune response. This view of immunoregulation confers a role of mobile brain or sensory organ to the SI.     

Systemic and cerebral hemodynamics and mental activity in marked neuro-emotional stress]

Changes in efficiency of mental activity and general and brain hemodynamics in students of physico-mathematical faculty when they solve problems on math analysis for 3 hours under conditions of pronounced neuro-emotional tension (NET) during examination have been experimentally studied. The results obtained from these studies are considered. It is shown that relation of higher nervous activity and general and brain hemodynamics is determined by efficiency of the activity, its energy provision (intensity), the level of NET and the rate of automated psychic reactions. A conclusion is made that efficiency of the activity is a basic system-forming factor in a relation arising between higher nervous activity, on the one hand, and general and brain hemodynamics, on the other hand. The higher is the efficiency, the lower are power requirements and the level of NET and the higher is the rate of automated psychic reactions: mental working capacity.     

免疫细胞内源性儿茶酚胺的免疫调节作用

机体内儿茶酚胺（catecholamines,CAs）包括去甲肾上腺素（norepinephrine,NE）、肾上腺素（epinephrine,E）和多巴胺（dopamine,DA）。CAs由神经元和内分泌细胞合成和分泌,其主要功能是调节心血管、呼吸和消化等内脏活动。近三十年来的研究说明,CAs也参与调控机体的免疫功能,但CAs的这种免疫调节作用一般视为神经和内分泌系统调节的介导作用。然而,近年来的研究发现,免疫细胞也能合成CAs,这是对传统观念的一种补充和提高。免疫细胞内存在经典的CAs代谢途径,既有合成CAs的酪氨酸羟化酶（tyrosine hydroxylase,TH）又有降解CAs的单胺氧化酶（monoamine oxidase,MAO）和儿茶酚氧位甲基移位酶（catechol-O-methyl transferase,COMT）。免疫细胞合成的内源性CAs可以调控细胞的增殖、分化、凋亡和细胞因子生成等多种免疫功能。CAs的这些作用可能主要通过自分泌或旁分泌途径作用于免疫细胞上相应受体和细胞内环磷酸腺苷（cyclicAMP,cAMP）实现。细胞内氧化应激机制可能也参与免疫细胞内源性CAs的免疫调节作用。此外,一些自身免疫性疾病如多发性硬化、风湿性关节炎可能也与免疫细胞内CAs的代谢异常有关。上述发现不仅为免疫系统有可能成为除神经和内分泌系统以外的第三个CA能系统提供了证据,而且为免疫系统内源性CAs的功能意义拓展了认识。     

Interaction of psychoemotional state and activity of the immune system

As shown, there are direct and reverse functional connections between nervous and immune systems. Different shifts in psychoemotional reactivity induced by chronic stress or mental depression are accompanied with immunological disturbance, and on the contrary, disorders of immune state may be source of changes in mental functions. The pineal hormone melatonin, anxiolytic and antidepressant drugs simultaneously influences on the cerebral structures and immune system. These effects may be important part of specific psychopharmacological activity of the drugs.     

Does exposure to HLA alloantigens trigger immunoregulatory mechanisms operative in both pregnancy and AIDS?

The complex biological processes responsible for regulating the immune system are presently the subject of considerable interest and study. New insight into this process comes from a variety of observations and it is the purpose of this communication to develop the hypothesis that two seemingly quite disparate observations point to a common biological mechanism bearing on immunoregulation. The observations concern the unique immunologic relationship between mother and fetus and the immunoregulatory abnormalities encountered in HIV-induced acquired immunodeficiency syndrome (AIDS). Exposure to foreign (allo) major histocompatibility complex (MHC) antigens can potentially occur during pregnancy, the transfusion of blood or blood products, or anal insemination. The hypothesis, in its simplest form, states that such MHC alloantigenic exposure triggers a sequence of immunoregulatory mechanisms resulting in immunosuppression and that this response has evolved in placental mammals as a means of protecting the fetus from maternal immune rejection and promoting optimal fetal development.     

DC-SIGN与免疫调节

树突状细胞(DC)是目前所知体内功能最强大的专职抗原递呈细胞,它既能启动初始免疫应答,也能负向调控免疫反应,具有独特的免疫调节功能。DC-SIGN属于DC表面C型凝集素受体超家族成员,它既是DC病原体模式识别和黏附受体,又作为DC特征性多功能免疫分子,参与DC免疫调节作用。DC-SIGN在调节DC黏附迁移及炎症反应,激活初始T细胞及启动免疫应答,以及病原体与肿瘤的免疫逃逸等诸多方面发挥重要作用,已日益受到人们的关注。而对DC-SIGN在天然免疫和获得性免疫中调节作用及其相关机制的更深入研究,可为临床相关疾病机制探讨与防治进一步提供新的有力依据和干预途径。     

WHO ARE PROSPECTIVE NEUROTICS?

Emotions of any kind and experienced at any age are etiologic factors of neuroses only in predisposed persons.Predisposed persons are those of neuropathic and psychoneuropathic constitution. This is characterized by excessive excitability and abnormal reactivity of the nervous system. This involves, in various degree and proportion, the autonomic nervous system as well as the higher cerebral functions including associative and emotional mental reactions.Objective signs of autonomic nervous imbalance can be detected by physical examination. In the mental sphere, psychoneurotic constitution can be recognized by emotional imbalance, excessive, inadequate, untimely reactions (“psychic dysmetry”).Neuropathic and psychoneuropathic constitution per se is compatible with perfect health. It deserves attention, however, in that its carriers may play an important role in cultural and social life and so exert a great suggestive influence on the mass of people.The type of neurosis or psychoneurosis and the symptoms of it depend chiefly on the constitutional morbid predisposition (constitutional biologic inferiority) of certain organs or organ systems and on the kind of emotional situations which the patient is unable to cope with.The great number of neuroses, psychoneuroses and psychosomatic diseases among patients consulting them makes it imperative that internists and general practitioners be capable of making the correct diagnosis and of carrying out the indicated treatments by “minor psychotherapy.”     

Spontaneous IFN-beta production. A common feature of natural suppressor systems

Natural suppression has been described in several immunologic systems in which splenocytes are not only incapable of generating an immune response, but are also able to non-specifically suppress normal splenocyte reactivity. Natural suppressor cells exist in such transitory immune deficiency states as graft vs host disease, irradiation recovery, and during neonatal development. We have found that when splenocytes from each of these three systems were placed in culture, IFN was produced spontaneously without stimulus. This spontaneous IFN production was augmented by the addition of IL-2 or granulocyte-macrophage-CSF to cell cultures. However, these lymphokines induced little or no IFN from normal splenocytes. This unusual IFN production is especially interesting since all samples have been typed to be IFN-beta. Additionally, greater IFN-beta was produced by these spleen cells during active suppression of the MLR of normal spleen cells. In fact, antibody to IFN-beta was shown to partially reverse the natural suppression mediated by graft vs host disease splenocytes in the MLR. Thus, IFN-beta production correlates extremely well with natural suppressor states. As mice begin to recover normal immune responses in all three systems, IFN-beta ceases to be produced spontaneously in culture. These findings establish a previously undescribed IFN-beta-producing splenic phenotype and suggest that IFN-beta may contribute to the immunoregulation of natural suppressor systems.     

Insulin resistance,selfish brain,and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases

Insulin resistance (IR) is a general phenomenon of many physiological states, disease states, and diseases. IR has been described in diabetes mellitus, obesity, infection, sepsis, trauma, painful states such as postoperative pain and migraine, schizophrenia, major depression, chronic mental stress, and others. In arthritis, abnormalities of glucose homeostasis were described in 1920; and in 1950 combined glucose and insulin tests unmistakably demonstrated IR. The phenomenon is now described in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity. This paper delineates that IR is either based on inflammatory factors (activation of the immune/ repair system) or on the brain (mental activation via stress axes). Due to the selfishness of the immune system and the selfishness of the brain, both can induce IR independent of each other. Consequently, the immune system can block the brain (for example, by sickness behavior) and the brain can block the immune system (for example, stress-induced immune system alterations). Based on considerations of evolutionary medicine, it is discussed that obesity per se is not a disease. Obesity-related IR depends on provoking factors from either the immune system or the brain. Chronic inflammation and/or stress axis activation are thus needed for obesity-related IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR. The new considerations towards IR are interrelated to the published theories of IR (thrifty genotype, thrifty phenotype, and others).     

Lack of TIM-3 immunoregulation in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the CNS white matter associated with T cell infiltrates and alterations of immune functions that can be measured in the peripheral immune system. TIM-3 has been identified as a central regulator of IFN-gamma-secreting type 1 Th (Th1) cells and immune tolerance. In this study, using a newly generated mAb against human TIM-3, we examined TIM-3 function on ex vivo CD4(+) T cells isolated from the circulation of healthy subjects and patients with MS. Blocking TIM-3 during T cell stimulation significantly enhanced IFN-gamma secretion in control subjects but had no effect in untreated patients with MS, demonstrating a defect in TIM-3 immunoregulation. Treatment with glatiramer acetate or IFN-beta reversed this functional defect. Reduced levels and altered kinetics of T cell TIM-3 expression, which was restored in treated patients, is one mechanism that can explain the loss of TIM-3 regulation of T cell function in untreated patients with MS. These data provide functional, mechanistic data for dysregulated TIM-3 immunoregulation in a human autoimmune disease and suggest that approved therapies for the treatment of MS may function in part by restoring TIM-3 immunoregulation of T cell function.     

Salt intake and mental distress among rural community-dwelling Japanese men

Background

Activated mineralocorticoid receptors influence the association between daily salt intake and blood pressure. A relatively low mineralocorticoid receptor function is reported to be a risk for mental distress such as depression. Since mental distress is also a known risk for hypertension and cardiovascular disease, understanding of the association between estimated daily salt intake and mental distress contributing to hypertension is important for risk estimation for cardiovascular disease. However, no single study has reported this association.

Methods

We conducted a cross-sectional study of 1014 Japanese men undergoing general health check-ups. Mental distress was diagnosed as a Kessler 6 scale score ≥5. We also classified mental distress by levels of hypertension. Estimated daily salt intake was calculated from a causal urine specimen.

Results

Independent from classical cardiovascular risk factors and thyroid disease, we found a significant inverse association between estimated daily salt intake and mental distress. When we analyzed for mental distress and hypertension, we also found a significant association. With the reference group being the lowest tertiles of estimated daily salt intake, the multivariable odds ratios (ORs) of mental distress and mental distress with hypertension for the highest tertiles were 0.50 (0.29–0.88) and 0.46 (0.22–0.96).

Conclusions

Lower estimated daily salt intake is a significant risk of mental distress for rural community-dwelling Japanese men. Since depression is reported to be associated with cardiovascular disease, risk estimation for the lower intake of salt on mental distress, especially for mental distress with hypertension, may become an important tool to prevent cardiovascular disease.     

The semaphorins

Semaphorins are secreted, transmembrane, and GPI-linked proteins, defined by cysteine-rich semaphorin protein domains, that have important roles in a variety of tissues. Humans have 20 semaphorins, Drosophila has five, and two are known from DNA viruses; semaphorins are also found in nematodes and crustaceans but not in non-animals. They are grouped into eight classes on the basis of phylogenetic tree analyses and the presence of additional protein motifs. The expression of semaphorins has been described most fully in the nervous system, but they are also present in most, or perhaps all, other tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. More recently, they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. A common theme in the mechanisms of semaphorin function is that they alter the cytoskeleton and the organization of actin filaments and the microtubule network. These effects occur primarily through binding of semaphorins to their receptors, although transmembrane semaphorins also serve as receptors themselves. The best characterized receptors for mediating semaphorin signaling are members of the neuropilin and plexin families of transmembrane proteins. Plexins, in particular, are thought to control many of the functional effects of semaphorins; the molecular mechanisms of semaphorin signaling are still poorly understood, however. Given the importance of semaphorins in a wide range of functions, including neural connectivity, angiogenesis, immunoregulation, and cancer, much remains to be learned about these proteins and their roles in pathology and human disease.     

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

How did the 2008-11 financial crisis affect work-related common mental distress? Evidence from 393 workplaces in Great Britain

This paper analyses how the 2008-11 financial crisis relates to work-related common mental distress of those with continuous employment during the crisis. The literature connecting the 2008-11 financial crisis to common mental distress (anti-depressant drug use, suicide, etc.) generally estimates a negative effect. We used a sample of 393 workplaces from the 2011 Work and Employment Relations Study (WERS) for which employers and worker representatives agreed on that the crisis affected the workplace. WERS then provides detailed questions about how the financial crisis affected the workplace. We use these questions to show which crisis-induced work-changes are important for work-related common mental distress. In the British-context, increased workload and changes in nonfinancial benefits of work are most relevant worsening work-related common mental distress by 1.8 and 0.9 on a scale from 0-30 respectively.     

Statement on Cancer Cures by the Cancer Commission of the C.M.A

In recent months there has been a recrudescence in the daily press of claims for certain alleged cancer cures. Most of these receive the scant attention which they deserve and are soon forgotten. A few receive sensational publicity and are a source of considerable distress, both psychic and economic, to patients with cancer. In order to bring up to date the opinion of the Cancer Commission on this general question, it was resolved at the regular meeting of the Commission held in Los Angeles, May 1951, that a suitable statement bearing on this subject be prepared and issued to the press or to interested persons. The following is the statement as approved by the Commission:     

抗菌肽的作用机制、生物活性及应用研究进展

抗菌肽广泛存在于生物界,是辅助生物机体抵抗外来病原体入侵的重要防御分子。抗菌肽不仅能抑制、杀灭多种细菌,而且具有抗真菌、抗寄生虫、抗病毒、抗肿瘤和免疫调节等生物学活性。抗菌肽的作用机制与传统抗生素不同,不仅具有广谱抗微生物作用,而且不易诱导机体产生耐药性,因此,在治疗临床耐药菌株方面具有极大的开发潜力。     

PSYCHIATRIC ASPECTS OF PSYCHOMOTOR EPILEPSY

Psychomotor or temporal lobe epilepsy is a frequently missed diagnosis. It is often confused with grand mal and petit mal epilepsy. At times it is the first symptom of an organic neurological disease. It is often masked as a psychiatric disorder or is associated with a mental illness without clinically detectable seizures.These psychic manifestations simulate all of the neuroses and major psychiatric states. Excitement states with amnesia may lead to violent antisocial behavior. All these manifestations may be aggravated by alcohol.Thalamic epilepsy shows itself in similar psychiatric manifestations and accounts for behavior disorder in children more than temporal lobe epilepsy. Atypical seizures with vegetative or emotional aura and a characteristic electroencephalogram differentiate it from temporal lobe epilepsy.Proper understanding of the varied manifestations, with positive electroencephalographic findings, leads to the correct diagnosis in most cases. All patients with unusual or atypical personality or psychiatric-like states should have careful electroencephalographic examination. Anticonvulsant therapy and other psychiatric treatment procedures can relieve most cases. Surgical therapy sometimes is necessary.     

IL-27 imparts immunoregulatory function to human NK cell subsets

Interleukin-27 (IL-27) is a cytokine with multiple roles in regulating the immune response, but its effect on human CD56(bright) and CD56(dim) NK cell subsets is unknown. NK cell subsets interact with other components of the immune system, leading to cytotoxicity or immunoregulation depending on stimulating factors. We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets. More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner. There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. Thus, understanding the role of IL-27 in NK cell function has important implications for treatment of autoimmune disorders.     

Beyond Critique: Rethinking Roles for the Anthropology of Mental Health

The current supremacy of the ‘bio-bio-bio’ model within the discipline of psychiatry has progressively marginalized social science approaches to mental health. This situation begs the question, what role is there for the anthropology of mental health? In this essay, I contend that there are three essential roles for the anthropology of mental health in an era of biological psychiatry. These roles are to (i) provide a meaningful critique of practices, beliefs, and movements within current psychiatry; (ii) illuminate the socio-cultural, clinical, and familial context of suffering and healing regarding emotional distress/mental illness; and (iii) act as a catalyst for positive change regarding healing, services and provisions for people with emotional distress/mental illness. My argument is unified by my contention that a credible anthropology of mental health intending to make a societal contribution should offer no opposition without proposition. In other words, any critique must be counter-balanced by the detailing of solutions and proposals for change. This will ensure that the anthropology of mental health continues to contribute critical knowledge to the understanding of mental suffering, distress, and healing. Such social and cultural approaches are becoming especially important given the widespread disenchantment with an increasingly dominant biological psychiatry.