The Neuroendocrine Immune Network

S. Freier

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315898094
• eBook ISBN: 9781351094092
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

This informative publication updates the study of interaction of the nervous and endocrine systems with the immune system in the body. It describes the anatomical basis of these interactions, reviewing the innervation of lymphoid tissue and mast cells. The book discusses the effect of the endocrine system on immune function, including the relation of sex to the immune response. Emphasis is given to opioids, substance P, neurotensin, vasoactive intestinal peptide, somatostatin and cholecystokinin. Also addressed is the immunoregulatory effect of leukotrienes and platelet-activating factors. Scrutinized within are stress as an aspect of neuro-immune interactions, and the central role of the hypothalamus in this context. The book reviews the eye and the gastrointestinal tract with respect to the coordination of the nervous, endocrine, and immune systems in serving these organs. This work is of particular value to those in immunology, endocrinology, gastroenterology, and developmental biology.

Chapter 1

THE ROLE OF THE NEURAL CREST IN THE DEVELOPMENT OF THE IMMUNE SYSTEM AND ENDOCRINE ORGANS

Dale E. Bockman and Margaret L. Kirby

TABLE OF CONTENTS

I.	Introduction
II.	Central Role of Thymus in Development of the Immune System
III.	Development of the Thymus, Thyroid, and Parathyroids
	A.	The Primitive Pharyngeal Region
	B.	Derivatives of Pharyngeal Epithelium
IV.	Development and Contributions of the Neural Crest
	A.	Formation
	B.	Neural Contributions
	C.	Mesenchymal Contributions
V.	Defective Development of the Thymus and Endocrine Organs
	A.	Clinical Data
	B.	Experimental Data
VI.	Conclusion
References

I. INTRODUCTION

Development of the immune system is dependent upon proper development of the thymus. Proper development of the thymus, in turn, is dependent upon contributions from the neural crest. Like the thymus, certain endocrine organs are dependent upon neural crest derivatives for differentiation. Furthermore, neural crest plays a key role in the formation of the neural network which serves lymphoid organs, including their blood supply.

The development of these interdependent elements is accomplished through an exquisitely timed series of differentiative steps, migrations, and interactions.

This chapter will first discuss the salient features of the differentiation of these elements, including the interactive features which control them. Next, it will consider clinical observations which have been interpreted as the result of failures in proper development of the neural crest, and experimental studies in which developmental defects have been induced as a means of trying to understand the interactive mechanisms involved.

II. CENTRAL ROLE OF THYMUS IN DEVELOPMENT OF THE IMMUNE SYSTEM

The thymus is a central lymphoid organ¹ which is necessary for the full development of the immune system. Within its specialized microenvironment, lymphocytes proliferate and differentiate by a process which is not antigen driven. Differentiated cells migrate from the thymus to populate peripheral lymphoid organs and tissues and to provide them with the thymus-dependent component of the immune system. Here, antigen-driven proliferation and differentiation constitute immune reactivity; failure of the thymus to provide a population of reactive cells to the peripheral lymphoid organs causes severe deficiencies in immune capability.

Thymic lymphoid development is initiated when the thymic primordium attracts lymphoid stem cells which arise in other places and circulate in the blood.^2,3 At this stage, the thymus is an epithelial bud with surrounding mesenchyme (Plate 1).^* Lymphoid stem cells enter the circulation from the yolk sac and fetal liver, and later from the bone marrow. They migrate from the blood vessels and enter the thymic primordium, where they proliferate and differentiate in the spaces between thymic epithelial cells.

Several subpopulations of lymphocytes are generated within the thymus;^{4, 5, 6} most die there. A small percentage of cells, carrying marker antigens which indicate their differentiative fate, leave the epithelial framework of the thymus to enter the bloodstream, and seed spleen, lymph nodes, and other peripheral lymphoid organs.

III. DEVELOPMENT OF THE THYMUS, THYROID, AND PARATHYROIDS

A. THE PRIMITIVE PHARYNGEAL REGION

As the early embryo assumes a cylindrical shape, a blind-ending tube of epithelium derived from endoderm is folded into the head region. This primitive foregut develops into the upper part of the digestive system. The pharyngeal part of the foregut is elaborated rapidly. The primitive pharyngeal cavity is limited in extent from floor to ceiling, but is expanded laterally, where it forms four or five pouchlike projections on each side. Pouch five may be considered a posterior extension of pouch four.⁷

The primitive pharynx gives rise to a number of important structures. Most of these lose their connections with the pharynx as they migrate or change their relative positions, retaining no evidence of their pharyngeal origin. The structures derived from the primitive pharynx, which are pertinent to the present discussion, include the thyroid and parathyroid glands, the ultimobrancial bodies, and the thymus.

B. DERIVATIVES OF PHARYNGEAL EPITHELIUM

Regional specializations of the epithelium lining the primitive pharyngeal cavity mark the earliest primordia of the glands in question. The thyroid appears first as a ventral bulge in the midline of the floor of the foregut. As elaboration of epithelial cells continues, it forms a distinct mass which is located between the first pair of pharyngeal pouches. After losing continuity with the pharynx, it assumes a progressively more posterior relative location due to the forward growth of the pharyngeal area. A connective tissue capsule is formed around the developing thyroid from local mesenchyme. The connective tissue of the thyroid is derived from the neural crest, as will be described later. The epithelial cells organize into the follicles which are typical of the definitive thyroid and which elaborate the thyroid hormones.

The ultimobranchial bodies are epithelial elaborations from the endoderm of the fifth (or posterior fourth) pharyngeal pouches. They receive mesenchymal contributions from the neural crest. Their hormone-producing cells may be derived from the neural crest.⁸ As the thyroid assumes a relatively more posterior position, the ultimobranchial bodies fuse with it. The hormone-producing cells derived from the ultimobranchial bodies become the C cells or parafollicular cells of the thyroid, which produce calcitonin (thyrocalcitonin).

The parathyroid glands develop as epithelial elaborations from the dorsal portion of each of the third and fourth pharyngeal pouches. They acquire connective tissue septa and capsules from surrounding mesenchyme and separate from the pharynx. They become attached to the thyroid, but remain four separate organs.

The thymic primordia, derived from the ventral portion of the third pharyngeal pouches, are at first hollow epithelial structures. The lumina of the thymic primordia disappear as cell proliferation continues. The primitive condition in which thymic spaces are continuous with the pharyngeal cavity is therefore not maintained, and eventually, the primordia lose all contact with the pharynx. The epithelial component of the thymus is modified to form a closed reticular framework as lymphocytes proliferate and differentiate within the interstitial spaces (Plate 1). The left and right lobes of the thymus unite with each other in the midline, forming the definitive single organ; migration and relative growth of the thymus leads to its final position in the upper part of the thoracic cavity in most mammals (multiple cervical lobes are present in birds). The connective tissue of the thymus is acquired from neural crest-derived mesenchyme which surrounds the primitive pharynx (Plate 1).

IV. DEVELOPMENT AND CONTRIBUTIONS OF THE NEURAL CREST

A. FORMATION

The neural crest is a transient structure which is present during the early formation of the nervous system and which subsequently expands to produce much of the peripheral nervous system and a large number of definitive nonnervous structures in the head and neck region. It produces a population of mesenchymal cells which interact with epithelial structures to induce their differentiation.

The primitive neural tube is formed when a thickened region of ectoderm (the neural plate) curves upward until its edges meet in the midline and fuse. The edges of the neural plate are continuous with unthickened ectoderm. This region projects upward as the plate rolls into a tube, forming the neural folds. The neural crest forms from the neural folds. As the tops of the neural tube meet and fuse, cells in the region where the ectoderm and neural tube meet divide rapidly. The neural crest thus formed projects laterally; its cells migrate from the edges, through extracellular matrix, to supply progeny to all parts of the body.^7,9

B. NEURAL CONTRIBUTIONS

The neural crest, with contributions from neural placodes, provides much of the peripheral nervous system.^7,9 This includes sensory ganglia of the brain and spinal cord and the autonomic nervous system. The moto...

Table of contents

• Cover
• Title Page
• Copyright Page
• Table of Contents
• Chapter 1 The Role of the Neural Crest in the Development of the Immune System and Endocrine Organs
• Chapter 2 Peripheral Innervation of Lymphoid Tissue
• Chapter 3 The Innervation of Mast Cells
• Chapter 4 Reciprocal Interactions between Mast Cells and the Endocrine System
• Chapter 5 Signaling Pathways of the Neurotransmitter-Immune Network
• Chapter 6 Neuroendocrine and Immune Function in the Capsaicin-Treated Rat: Evidence for Afferent Neural Modulation In Vivo
• Chapter 7 Differential Sex-Associated Differences in Immune Responses to and Osteoneogenesis of Ectopically Transplanted Fetal Bone Allografts: Importance of H2 and Non-H2 Encoded Alloantigens
• Chapter 8 Augmentation of Natural Immunity by Conditioning and Possible Mechanisms of Enhancement
• Chapter 9 Hypothalamic-Immune Interactions: Modulation of Immune Function by Electrolytic and Chemical Lesions in the Central Nervous System
• Chapter 10 Immunoregulation by Leukotrienes and Platelet-Activating Factor
• Chapter 11 Immunoregulatory Activity of Endogenous Opioids
• Chapter 12 Stress Neuropeptides, Immunity, and Neoplasia
• Chapter 13 Modulation of Phagocyte Activity by Substance P and Neurotensin
• Chapter 14 The Role of Substance P, Somatostatin and Vasoactive Intestinal Peptide in Modulation of Mucosal Immunity
• Chapter 15 Hormonal Influence on the Secretory Immune System of the Eye
• Chapter 16 The Neuroendocrine-Immune Network in the Gastrointestinal Tract
• Index