CNS–immune system interactions: Conditioning phenomena

1985 ◽  
Vol 8 (3) ◽  
pp. 379-395 ◽  
Author(s):  
Robert Ader ◽  
Nicholas Cohen
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Immune Responses ◽  
Self Regulation ◽  
Immunosuppressive Drug ◽  
Conditioned Stimuli ◽  
Biological Impact ◽  
Experimental Conditions ◽  
Progression Of Disease ◽  
The Brain

AbstractConverging data from different disciplines indicate that central nervous system processes are capable of influencing immune responses. This paper concentrates on recent studies documenting behaviorally conditioned suppression and enhancement of immunity. Exposing rats or mice to a conditioned stimulus previously paired with an immunomodulating agent results in alterations in humoral and cell-mediated immune responses to antigenic stimuli, and unreinforced reexposures to the conditioned stimuli result in extinction of the conditioned response. Although the magnitude of such conditioning effects has not been large, the phenomenon has been independently verified under a variety of experimental conditions. The biological impact of conditioned alterations in immune function is illustrated by studies in which conditioning operations were applied in the pharmacotherapy of autoimmune disease in New Zealand mice. In conditioned animals, substituting conditioned stimuli for active drugs delays the onset of autoimmune disease relative to nonconditioned animals using a dose of immunosuppressive drug that, by itself, is ineffective in modifying the progression of disease. The hypothesis that such conditioning effects are mediated by elevations in adrenocortical steroid levels receives no support from available data. Despite its capacity for self-regulation, it appears that the immune system is integrated with other psychophysiological processes and subject to modulation by the brain.

scholarly journals Imd pathway-specific immune assays reveal NF-κB stimulation by viral RNA PAMPs in Aedes aegypti Aag2 cells

2020 ◽  
Author(s):  
Tiffany A. Russell ◽  
Andalus Ayaz ◽  
Andrew D. Davidson ◽  
Ana Fernandez-Sesma ◽  
Kevin Maringer
Keyword(s):  
Immune System ◽  
Aedes Aegypti ◽  
Immune Responses ◽  
Health Impact ◽  
Global Public Health ◽  
Toll Pathway ◽  
Experimental Conditions ◽  
Imd Pathway ◽  
Arboviral Diseases ◽  
Transgenic Insects

ABSTRACTBackgroundThe mosquito Aedes aegypti is a major vector for the arthropod-borne viruses (arboviruses) chikungunya, dengue, yellow fever and Zika viruses. Vector immune responses pose a major barrier to arboviral transmission, and transgenic insects with altered immunity have been proposed as tools for reducing the global public health impact of arboviral diseases. However, a better understanding of virus-immune interactions is needed to progress the development of such transgenic insects. Although the NF-κB-regulated Toll and ‘immunodeficiency’ (Imd) pathways are increasingly thought to be antiviral, relevant pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) remain poorly characterised in A. aegypti.Methodology/Principle FindingsWe developed novel RT-qPCR and luciferase reporter assays to measure induction of the Toll and Imd pathways in the commonly used A. aegypti-derived Aag2 cell line. We thus determined that the Toll pathway is not inducible by exogenous stimulation with bacterial, viral or fungal stimuli in Aag2 cells under our experimental conditions. We used our Imd pathway-specific assays to demonstrate that the viral dsRNA mimic poly(I:C) is sensed by the Imd pathway, likely through intracellular and extracellular PRRs. The Imd pathway was also induced during infection with the model insect-specific virus cricket paralysis virus (CrPV).Conclusions/SignificanceOur demonstration that a general PAMP shared by many arboviruses is sensed by the Imd pathway paves the way for future studies to determine how viral RNA is sensed by mosquito PRRs at a molecular level. Our data also suggest that studies measuring inducible immune pathway activation through antimicrobial peptide (AMP) expression in Aag2 cells should be interpreted cautiously given that the Toll pathway is not responsive under all experimental conditions. With no antiviral therapies and few effective vaccines available to treat arboviral diseases, our findings provide new insights relevant to the development of transgenic mosquitoes as a means of reducing arbovirus transmission.AUTHOR SUMMARYThe mosquito Aedes aegypti, found globally across the tropics and subtropics, transmits viral diseases with a significant global public health impact, including chikungunya, dengue, yellow fever and Zika viruses. There are no antiviral drugs to treat these diseases and few effective vaccines. One way of reducing the global burden of mosquito-borne diseases would be to develop genetically modified mosquitoes unable to transmit viruses. One approach would be to alter the mosquitoes’ immune system to allow them to better fight viral infections. To do so, we first need to understand how viruses are detected by the mosquito immune system. We developed new methods of measuring immune responses in laboratory-cultured mosquito cells and used them to show that one specific arm of the immune system, called the ‘Imd pathway’, can detect the RNA that constitutes the genome of mosquito-borne viruses. These findings pave the way for future immune studies that could inform the development of transmission-incompetent mosquitoes. We also found that another arm of the immune system, called the ‘Toll pathway’, is not functional under any experimental conditions used in this study. This finding has implications for how different laboratories interpret data from these particular cultured cells.

scholarly journals Serum bactericidal activity as indicator of innate immunity in pacu Piaractus mesopotamicus (Holmberg, 1887)

2013 ◽  
Vol 65 (6) ◽  
pp. 1745-1751 ◽  
Author(s):  
J.D. Biller-Takahashi ◽  
L.S. Takahashi ◽  
F. Pilarski ◽  
F.A. Sebastião ◽  
E.C. Urbinati
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Bactericidal Activity ◽  
Aeromonas Hydrophila ◽  
Activity Assay ◽  
Experimental Conditions ◽  
Piaractus Mesopotamicus ◽  
Colony Forming Unit ◽  
Serum Bactericidal Activity ◽  
Protective Proteins

The immune system of teleost fish has mechanisms responsible for the defense against bacteria through protective proteins in several tissues. The protein action can be evaluated by serum bactericidal activity and this is an important tool to analyze the immune system. Pacu, Piaractus mesopotamicus, is one of the most important fish in national aquaculture. However there is a lack of studies on its immune responses. In order to standardize and assess the accuracy of the serum bactericidal activity assay, fish were briefly challenged with Aeromonas hydrophila and sampled one week after the challenge. The bacterial infection increased the concentration of protective proteins, resulting in a decrease of colony-forming unit values expressed as well as an enhanced serum bactericidal activity. The protocol showed a reliable assay, appropriate to determine the serum bactericidal activity of pacu in the present experimental conditions.

Immune and Inflammatory Responses to Stroke: Good Or Bad?

2008 ◽  
Vol 3 (4) ◽  
pp. 254-265 ◽  
Author(s):  
P. A. McCombe ◽  
S. J. Read
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Regulatory Lymphocytes ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Inflammatory and immune responses play important roles following ischaemic stroke. Inflammatory responses contribute to damage and also contribute to repair. Injury to tissue triggers an immune response. This is initiated through activation of the innate immune system. In stroke there is microglial activation. This is followed by an influx of lymphocytes and macrophages into the brain, triggered by production of pro-inflammatory cytokines. This inflammatory response contributes to further tissue injury. There is also a systemic immune response to stroke, and there is a degree of immunosuppression that may contribute to the stroke patient's risk of infection. This immunosuppressive response may also be protective, with regulatory lymphocytes producing cytokines and growth factors that are neuroprotective. The specific targets of the immune response after stroke are not known, and the details of the immune and inflammatory responses are only partly understood. The role of inflammation and immune responses after stroke is twofold. The immune system may contribute to damage after stroke, but may also contribute to repair processes. The possibility that some of the immune response after stroke may be neuroprotective is exciting and suggests that deliberate enhancement of these responses may be a therapeutic option.

scholarly journals Immunoceptive inference: why are psychiatric disorders and immune responses intertwined?

2021 ◽  
Vol 36 (3) ◽  
Author(s):  
Anjali Bhat ◽  
Thomas Parr ◽  
Maxwell Ramstead ◽  
Karl Friston
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Psychiatric Disorders ◽  
Message Passing ◽  
Genetic Mutations ◽  
Active Inference ◽  
Sensory Attenuation ◽  
The Brain ◽  
Neuropsychiatric Conditions

AbstractThere is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this would require a step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems?

Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Associative Learning ◽  
Placebo Response ◽  
Immunosuppressive Drug ◽  
Immune Functions ◽  
Placebo Effects ◽  
New Therapeutic Approaches ◽  
Biological Variables ◽  
Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

Review of Self-regulation of the Brain and Behavior.

1985 ◽  
Vol 30 (12) ◽  
pp. 999-999
Author(s):  
Gerald S. Wasserman
Keyword(s):  
Self Regulation ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain

Effect of combined citicoline and glutamate antibodies on acute, generalized convusions induced by pentylenetetrazole in mice

2018 ◽  
pp. 24-29
Author(s):  
М.Н. Карпова ◽  
Л.В. Кузнецова ◽  
Н.Ю. Клишина ◽  
Л.А. Ветрилэ
Keyword(s):  
Drug Combination ◽  
Subcutaneous Injection ◽  
Seizure Activity ◽  
Experimental Conditions ◽  
Slow Progression ◽  
Experiment Control ◽  
Effective Doses ◽  
Experimental Justification ◽  
Series Of Experiments ◽  
The Brain

Цель исследования. На 2 моделях острых генерализованных судорог (ОГС), вызванных конвульсантом пентилентетразолом (ПТЗ), изучить эффективность сочетанного применения ноотропа цитиколина - препарата с противосудорожным действием, нейрорегенеративной, нейропротекторной активностью и антител (АТ) к глутамату, обладающих противосудорожной активностью. Методика. Эксперименты выполнены на мышах-самцах линии C57Bl/6 (n = 87) массой 22-28 г. Эффективность сочетанного применения цитиколина и АТ к глутамату изучали на двух моделях ОГС. Выполнено 2 серии экспериментов. В 1-й серии ОГС вызывали внутривенным введением 1% раствора ПТЗ со скоростью 0,01 мл/с. Для изучения эффективности сочетанного применения препаратов определяли минимальное противосудорожное действие цитиколина (Цераксон, «Nicomed Ferrer Internaсional, S.A.») и АТ к глутамату при их внутрибрюшинном введении. С этой целью цитиколин вводили в дозах 500 и 300 мг/кг за 1 ч до введения ПТЗ, АТ к глутамату - в дозах 5 и 2,5 мг/кг за 1 ч 30 мин до введения ПТЗ. АТ к глутамату получали путем гипериммунизации кроликов соответствующим конъюгированным антигеном. Во 2-й серии ОГС вызывали подкожным введением ПТЗ в дозе 85 мг/кг. Для изучения эффективности сочетанного действия изучаемых препаратов последние вводили в минимально действующих дозах, установленных в 1-й серии экспериментов. Контролем во всех сериях опытов служили животные, которым вводили в аналогичных условиях и в том же объеме физиологический раствор. Результаты. Показано, что сочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах (300 и 2,5 мг/кг соответственно) при моделировании ОГС не вызывало повышения судорожной активности мозга и усиления противосудорожных свойств препаратов. Заключение. Cочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах не вызывало повышения судорожной активности мозга, что свидетельствует о безопасности совместного применения препаратов. Проведенное исследование может служить также экспериментальным обоснованием возможности использования сочетанного применения данных препаратов при судорогах с целью замедления прогрессирования нейродегенеративных процессов и благоприятного влияния на когнитивные функции. Aim. To study the effectivity of a combination of citicoline, a nootropic substance with neuroregenerative, neuroprotective, and anticonvulsant actions, and glutamate antibodies (АB) with an anticonvulsant action in two models of acute generalized convulsions (AGC) caused by the convulsant pentylenetetrazole (PTZ). Methods. Experiments were conducted on C57Bl/6 mice (n = 87) weighing 22-28 g. Effects of combined citicoline and glutamate АB were studied on two models of AGС. In the first series of experiments, AGС was induced by intravenous infusion of a 1% PTZ solution at 0.01 ml/sec. In the second series, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate efficacy of the drug combination minimum intraperitoneal anticonvulsant doses of citicoline (Tserakson, Nicomed Ferrer Internacional, S.A.) and glutamate АB were determined. To this purpose, citicoline was administered at 500 and 300 mg/kg 1 h prior to PTZ, and glutamate АB was administered at 5 and 2.5 mg/kg 90 min prior to PTZ. Glutamate АB was obtained by hyperimmunization of rabbits with a respective conjugated antigen. In the second series of experiments, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate the effect of the drug combination, the drugs were administered at the minimum effective doses determined in the first series of experiment. Control animals were injected with the same volume of saline in the same experimental conditions. Results. The combination of citicoline and glutamate AB used at minimum effective doses of 300 and 2.5 mg/kg, respectively, did not increase the seizure activity in the brain and enhanced anticonvulsant properties of the drugs in two models of AGС. Conclusion. The combination of citicoline and glutamate AT at minimum effective doses did not increase the convulsive activity in the brain, which supported safety of the drug combination. Besides, this study can serve as an experimental justification for using the drug combination in convulsions to favorably influence cognitive functions and slow progression of neurodegenerative processes.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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