The sympathetic nervous system modulates antibody response to thymus-independent antigens

doi:10.1016/0165-5728(81)90012-6

Journal of Neuroimmunology

Volume 1, Issue 1, March 1981, Pages 101-105

https://doi.org/10.1016/0165-5728(81)90012-6 Get rights and content

Abstract

Sympathetic nerve endings were destroyed with 6-hydroxydopamine (6-OHDA) and the response to thymus-dependent and -independent antigens compared in 6-OHDA-treated and control mice. A significantly enhanced plaque-forming cell response to 2 thymus-independent antigens was observed in the 6-OHDA-treated mice; in contrast the response to a thymus-dependent antigen was normal. The findings point to selective modulation of antibody response by the sympathetic nervous systems.

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Cited by (107)

Neuronal regulation of B-cell immunity: Anticipatory immune posturing?
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Citation Excerpt :
On the other hand, it is also evident that whether and to what extent sympathetic signals enhance or inhibit antibody responses could not be predicted in a straightforward manner, at least not by simply adding together in vitro effects observed for each cell type. Mainly by the approach of chemical sympathectomy, numerous studies have indicated that sympathetic signals promote the T-dependent antibody response (Madden et al., 1989, 1994a; Hall et al., 1982) while inhibiting the T-independent response (Miles et al., 1981). A genetic approach of Adrb2 gene ablation fails to demonstrate dramatic defects in adaptive immunity (Sanders et al., 2003), while compensatory receptor signaling and canceling effects among different responding immune cell circuits cannot be ruled out.
The brain may sense, evaluate, modulate, and intervene in the operation of immune system, which would otherwise function autonomously in defense against pathogens. Antibody-mediated immunity is one arm of adaptive immunity that may achieve sterilizing protection against infection. Lymphoid organs are densely innervated. Immune cells supporting the antigen-specific antibody response express receptors for neurotransmitters and glucocorticoid hormones, and they are subjected to collective regulation by the neuroendocrine and the autonomic nervous system. Emerging evidence reveals a brain-spleen axis that regulates antigen-specific B cell responses and antibody-mediated immunity. In this article, we provide a synthesis of those studies as pertinent to neuronal regulation of B cell responses in secondary lymphoid organs. We propose the concept of defensive immune posturing as a brain-initiated top-down reaction in anticipation of potential tissue injury that requires immune protection.
Sympathetic modulation of immunity: Relevance to disease
2008, Cellular Immunology
Citation Excerpt :
Th cell-dependent antibody production can be modulated by the SNS in vivo, which indicates that NE is likely to be required for optimal antibody production, and may directly affect either B cells and/or Th cells that participate in the response. In vivo studies employing chemical sympathectomy in adult rodents prior to antigen challenge with a T-cell dependent antigen reduces [54,91,145,226–228] or enhances [13,229,230] antibody production. Chemical sympathectomy in C57Bl/6 mice, a strain with a predominant Th1 antibody profile, enhances Th1-associated serum IgG2a and Th2-associated IgG1 production after immunization with keyhole limpet hemocyanin (KLH).
Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far has focused on neural-immune modulation in secondary lymphoid organs, has revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS–immune interaction may enhance immune readiness during disease- or injury-induced ‘fight’ responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.
Adrenergic regulation of immunity
2007, Psychoneuroimmunology, Two-Volume Set
Adrenergic Regulation of Immunity
2006, Psychoneuroimmunology
Innervation of lymphoid organs: Clinical implications
2006, Clinical Neuroscience Research
Host defense against pathogens is regulated by cross-talk between two major adaptive systems of the body—the nervous and immune systems. This bidirectional communication is essential for maintaining homeostasis. Sympathetic nerves that innervate lymphoid tissues provide one of the major outflows from the brain to regulate tissue repair and host defense. This review focuses on the role of (sympathetic nervous system) SNS in neuroimmune regulation, an area that has received much less attention than the other major immunoregulatory pathway, the hypothalamo–pituitary–adrenal (HPA) axis. Research over the past 25 years has demonstrated that norepinephrine (NE) fulfills the criteria for neurotransmission in lymphoid tissue, with both primary and secondary immune organs receiving an extensive supply of sympathetic nerves that directly contact with immunocytes. Under stimulation, NE released from terminals in secondary lymphoid organs interacts with adrenergic receptors (AR) expressed on immune cells to affect the development, trafficking, circulation, proliferation, cytokine production, and the functional activity of variety of lymphoid and myeloid cells. Our knowledge of the role of sympathetic nerves in modulating hematopoietic functions of primary lymphoid organs (bone marrow and thymus) and mucosal immunity are extremely limited. While the immune system is not absolutely dependent upon signals from the brain to function, sympathetic-immune modulation may drive host defense toward protection against, or progression toward, immune-related diseases. Additionally, signals from the (SNS) may enhance immune readiness during disease- or injury-induced ‘fight-or-flight’ responses. A better understanding of neural–immune interactions may foster the development of strategies for treating immune-mediated diseases, particularly where neuroimmune cross-talk may be dysregulated.
Increased splenocyte mitogenesis following sympathetic denervation in Xenopus laevis
2005, Developmental and Comparative Immunology
Studies in mammals reveal that ablation of the sympathetic nervous system (SNS) can alter in vivo and in vitro parameters of immunity. To shed some light on the phylogenetic history of the interactions between the SNS and the immune system, we studied the effects of chemical sympathectomy on the proliferative response of frog splenocytes to mitogens. Adult Xenopus laevis were injected with 6-hydroxydopamine 3 days before removal of spleen cells for culture with mitogens. Splenocytes from sympathectomized frogs exhibited an increased proliferative response to the T cell mitogens PHA and ConA and the B cell mitogen, LPS. That sympathectomy appears to effect a release from tonic inhibition by the SNS in Xenopus is consistent with comparable experiments in mice. It also reveals a phylogenetically ancient origin for SNS-immune system communications.

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^☆: This work was supported in part by a training grant (5T32-NS-07113) from the National Institutes of Health (KM), a grant (No. 80-5) from the American Cancer Society, Illinois Division (EC-S and BGWA), a grant from the National Foundation of the March of Dimes (JQ), and NIH grant No. AI-14530 (JQ). Dr. Quintáns is the recipient of a RCDA from the NIH (AI00268).

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The sympathetic nervous system modulates antibody response to thymus-independent antigens☆

Abstract

Cell Immunol.

Cell. Immunol.

The occurrence in rabbit of an acute phase protein analogous to human C-reactive protein

J. Exp. Med.

Lymphocyte subpopulations in the thymus

Transplant. Rev.

Hypothalamic changes during the immune response

Europ. J. Immunol.

Modulation of inflammation and immunity by cyclic AMP

Science

Modulatory effect of the sympathetic nervous system on neuroblastoma tumor growth

Cancer Res.

Further improvements in the plaque technique for detecting single antibody-forming cells

Immunology

Cyclic nucleotides in lymphocyte function

Ann. N.Y. Acad. Sci.

The role of cyclic 3′5′-adenosine monophosphate in the specific cytolytic activity of lymphocytes

J. Immunol.