Comprehensive Physiology Wiley Online Library

Regional Neural Regulation of Immunity: Anatomy and Function

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 The Autonomic Nervous System
1.1 Overview
1.2 Central Control
1.3 Terminal Distribution of Fibers
1.4 Summary
2 The Neuroendocrine System
3 The Immune System
4 Acute‐Phase Response
5 Innervation of Primary, Secondary, and Tertiary Immune Tissues
5.1 Primary Immune Tissues
5.2 Thymus Innervation
5.3 Secondary Immune Tissues
5.4 Tertiary Immune Tissues
5.5 Summary
6 Summary and Conclusions
Figure 1. Figure 1.

ANS signals from nonmyelinated bundles of nerve fibers are dispersed between the stromal cells of peripheral glands. The varicosities release neurotransmitters into the interstitial space of the glands affecting many cells which express ANS transmitter receptors.

Figure 2. Figure 2.

Schematic representation of the postnatal anatomic developmental pathways of the education and migration of immunocytes. Precursor cells derived primarily from the bone marrow migrate to the thymus to be selected, or “educated,” as antigen‐presenting T cells. B cells (in the case of mammals) are selected in the bone marrow, whereas in Aves, such as chickens, B‐cell education is carried out in a specialized organ, the bursa. Educated T and B cells migrate from these primary immune tissues to the secondary and tertiary immune tissues. Accessory cells are also exposed to bone marrow factors and distributed to primary, secondary, and tertiary immune tissues. The ratio and type of immunocytes present in the different immune tissues at any given time is dependent on many events, such as the type of trauma (pathogenic, puncture wound, etc.), location and severity, as well as signal molecules derived from the immune, endocrine, and nervous systems.

Figure 3. Figure 3.

Simplistic schematic representation of the major pathway leading to and during the acute‐phase response (APR). Following trauma, a local response to the site of damage occurs. If the injury is severe enough, alarm cytokines released by activated macrophages and other local cell types precipitate a cascade of systemic molecular events comprising the APR. ICAM, intracellular adhesion molecule; IL, interleukin; TNF, tumor necrosis factor; TGF, transforming growth factor; MCP, macrophage chemotatic protein.

Figure 4. Figure 4.

The nerves that innervate the bone branch at the nutrient foramen before entering the bone. One segment of the nerve enters the marrow, divides and supplies the arterial component of the marrow's circulation and to some extent the sinusoidal parts and parenchymal elements. The release of ANS neurotransmitters into the bone marrow can influence cells which express sympathetic, parasympathetic and peptidnergic receptors.

Figure 5. Figure 5.

Schematic and photomicrographic representations of the innervation of the thymus. 1: A line drawn from level C‐2 in the spinal cord to a photomicrograph shows three cells labeled after simultaneous injection of fluorogold into the thymus and horseradish peroxidase (HRP) into adjacent tissue. The cells are not double‐labeled, indicating that the cells of the spinal cord project to independent structures in this region rather than sending collaterals of single nerve cells . 2: A line drawn from the nucleus retrofacial (E, NRF), to a photomicrograph of cells labeled after simultaneous injection of fluorogold into the thymus and HRP into adjacent tissue. Again, the lack of double labeling indicates a separate projection of these neurons to the thymus . 3: (a) Labeled neurons of the nodose ganglia following HRP injection into the thymus (55). (b) Acetylcholinesterase histochemistry of vagal nerves deep within the thymus. Note ramification of the nerve within the gland . (c) Neurons labeled with HRP in the superior cervical ganglia following injection of HRP into the thymus. (d) Catecholaminergic sympathetic innervation is derived from the superior cervical ganglia and other ganglia of the cervical sympathetic chain .

Figure 6. Figure 6.

Distribution of sympathetic nerves within a splenic lymph nodule. t, antigen‐sensitive T lymphocytes; T, activated T lymphocytes; b, antigen‐sensitive B lymphocytes; P, activated plasmacytes.

Figure 7. Figure 7.

Schematic and photomicrographic representations of the changes in calcitonin gene‐related peptide (CGRP) immunoreactivity in five damage models that target different regions of hippocampal formation. A: Photomicrograph showing the distribution of CGRP in the intermolecular layer (IML) of the dentate gyrus. Two models, adrenalectomy (B) and colchicine injection (C,D), involve neuronal death in the granule cell layer (GCL) of the dentate gyrus and in the polymorphic region of the dentate gyrus (PoMDG) . Note the change in CGRP immunoreactivity in the IML activity as compared to control (A) in these two models. The third model, kainic acid (E), induced seizures and caused damage to cells primarily in the region of CA3b and c and temporal change in CGRP immunoreactivity in cells of the PoMDG. The fourth model, utilizing the neurotoxin trimethyltin, shows a marked change in the CA1 hilus and CA3 regions of the hippocampus and intense CGRP immunoreactivity in neurons of the PoMDG. The fifth model, ischemia, induces a marked change in CGRP immunoreactivity within neurons of the dorsal subiculum (DS) and the CA1 region . In all five models, expression of CGRP immunoreactivity is associated with the region of injury .

Figure 8. Figure 8.

Schematic representation of the autonomic nervous system efferent (parasympathetic and sympathetic) distribution to the tissues and organs of the body. NS, nervous system; g., gland; mesen., mesenteric; n., nerve; c, cervical spine; t., thoracic spine, l., lumbar spine; s., sacrum.



Figure 1.

ANS signals from nonmyelinated bundles of nerve fibers are dispersed between the stromal cells of peripheral glands. The varicosities release neurotransmitters into the interstitial space of the glands affecting many cells which express ANS transmitter receptors.



Figure 2.

Schematic representation of the postnatal anatomic developmental pathways of the education and migration of immunocytes. Precursor cells derived primarily from the bone marrow migrate to the thymus to be selected, or “educated,” as antigen‐presenting T cells. B cells (in the case of mammals) are selected in the bone marrow, whereas in Aves, such as chickens, B‐cell education is carried out in a specialized organ, the bursa. Educated T and B cells migrate from these primary immune tissues to the secondary and tertiary immune tissues. Accessory cells are also exposed to bone marrow factors and distributed to primary, secondary, and tertiary immune tissues. The ratio and type of immunocytes present in the different immune tissues at any given time is dependent on many events, such as the type of trauma (pathogenic, puncture wound, etc.), location and severity, as well as signal molecules derived from the immune, endocrine, and nervous systems.



Figure 3.

Simplistic schematic representation of the major pathway leading to and during the acute‐phase response (APR). Following trauma, a local response to the site of damage occurs. If the injury is severe enough, alarm cytokines released by activated macrophages and other local cell types precipitate a cascade of systemic molecular events comprising the APR. ICAM, intracellular adhesion molecule; IL, interleukin; TNF, tumor necrosis factor; TGF, transforming growth factor; MCP, macrophage chemotatic protein.



Figure 4.

The nerves that innervate the bone branch at the nutrient foramen before entering the bone. One segment of the nerve enters the marrow, divides and supplies the arterial component of the marrow's circulation and to some extent the sinusoidal parts and parenchymal elements. The release of ANS neurotransmitters into the bone marrow can influence cells which express sympathetic, parasympathetic and peptidnergic receptors.



Figure 5.

Schematic and photomicrographic representations of the innervation of the thymus. 1: A line drawn from level C‐2 in the spinal cord to a photomicrograph shows three cells labeled after simultaneous injection of fluorogold into the thymus and horseradish peroxidase (HRP) into adjacent tissue. The cells are not double‐labeled, indicating that the cells of the spinal cord project to independent structures in this region rather than sending collaterals of single nerve cells . 2: A line drawn from the nucleus retrofacial (E, NRF), to a photomicrograph of cells labeled after simultaneous injection of fluorogold into the thymus and HRP into adjacent tissue. Again, the lack of double labeling indicates a separate projection of these neurons to the thymus . 3: (a) Labeled neurons of the nodose ganglia following HRP injection into the thymus (55). (b) Acetylcholinesterase histochemistry of vagal nerves deep within the thymus. Note ramification of the nerve within the gland . (c) Neurons labeled with HRP in the superior cervical ganglia following injection of HRP into the thymus. (d) Catecholaminergic sympathetic innervation is derived from the superior cervical ganglia and other ganglia of the cervical sympathetic chain .



Figure 6.

Distribution of sympathetic nerves within a splenic lymph nodule. t, antigen‐sensitive T lymphocytes; T, activated T lymphocytes; b, antigen‐sensitive B lymphocytes; P, activated plasmacytes.



Figure 7.

Schematic and photomicrographic representations of the changes in calcitonin gene‐related peptide (CGRP) immunoreactivity in five damage models that target different regions of hippocampal formation. A: Photomicrograph showing the distribution of CGRP in the intermolecular layer (IML) of the dentate gyrus. Two models, adrenalectomy (B) and colchicine injection (C,D), involve neuronal death in the granule cell layer (GCL) of the dentate gyrus and in the polymorphic region of the dentate gyrus (PoMDG) . Note the change in CGRP immunoreactivity in the IML activity as compared to control (A) in these two models. The third model, kainic acid (E), induced seizures and caused damage to cells primarily in the region of CA3b and c and temporal change in CGRP immunoreactivity in cells of the PoMDG. The fourth model, utilizing the neurotoxin trimethyltin, shows a marked change in the CA1 hilus and CA3 regions of the hippocampus and intense CGRP immunoreactivity in neurons of the PoMDG. The fifth model, ischemia, induces a marked change in CGRP immunoreactivity within neurons of the dorsal subiculum (DS) and the CA1 region . In all five models, expression of CGRP immunoreactivity is associated with the region of injury .



Figure 8.

Schematic representation of the autonomic nervous system efferent (parasympathetic and sympathetic) distribution to the tissues and organs of the body. NS, nervous system; g., gland; mesen., mesenteric; n., nerve; c, cervical spine; t., thoracic spine, l., lumbar spine; s., sacrum.

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Karen Bulloch. Regional Neural Regulation of Immunity: Anatomy and Function. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 353-379. First published in print 2001. doi: 10.1002/cphy.cp070417