IMMUNOLOGY - Roit I. - Mir 2000

Chapter 13. Regulation of the Immune Response

NEUROENDOCRINE REGULATION OF THE IMMUNE RESPONSE

It has long been known that stressful situations can suppress immune Functions, such as the body's ability to fight off infections. Abundant evidence indicates a close interplay between the nervous, endocrine, and immune systems. In general, Central Nervous system processes can influence immune function through two primary pathways, as illustrated in Fig. 13.15.

✵ Most lymphoid Tissues receive direct sympathetic innervation, supplying both the Blood Vessels passing through the tissue and the lymphocytes themselves.

✵ The Nervous System directly or indirectly controls the secretion of various Hormones, notably corticosteroids, Growth Hormone, thyroxine, and adrenaline.

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Fig. 13.15. Potential pathways of communication between the endocrine, nervous, and immune systems. Blue arrows indicate sympathetic innervation, red arrows represent hormonal effects, and white arrows denote putative pathways whose effector molecules have not yet been identified.

Lymphocytes express receptors for a wide array of hormones, Neurotransmitters, and Neuropeptides, including receptors for Steroids, catecholamines (adrenaline and noradrenaline), enkephalins, endorphins, substance P, and vasoactive intestinal peptide (VIP). The level of receptor expression and cellular reactivity varies among different lymphocyte and monocyte subsets, meaning that the effects of various mediators also depend on context. Nevertheless, of particular importance to The Immune System is the regulation mediated by corticosteroids, endorphins, and enkephalins—agents released during stress that exert immunosuppressive effects in vivo. The in vitro effects of endorphins vary considerably depending on the experimental setup and dosage, being suppressive at some doses and immunostimulatory at others. However, corticosteroids undoubtedly serve as a critical feedback regulator of the Immune Response. Furthermore, lymphocytes can respond to corticotropin-releasing hormone by synthesizing their own АКТГ, which in turn induces corticosteroid secretion.

Evidence indicates that corticosteroids inhibit cytokine production by Th1 Cells without affecting the Th2 response. In addition, they induce The production of ТФРβ, which can suppress immune responses. It is hypothesized that low plasma corticosteroid levels in Lewis rats account for their heightened susceptibility to various autoimmune conditions; following experimental autoimmune encephalomyelitis (EAE) induction, spontaneous recovery in these animals correlates with rising blood corticosteroid levels, whereas adrenalectomized animals fail to recover. The Role of steroids in disease susceptibility is further demonstrated in PVG rats: while normally resistant to EAE, these animals become susceptible following adrenalectomy.

The crosstalk between the neuroendocrine and immune systems is bidirectional. Cytokines, particularly ИЛ-1 and ИЛ-6, act in both directions, serving as key modulators of this interaction. These cytokines are potent stimulators of adrenal corticosteroid production via their effects on corticotropin-releasing hormone. Besides being produced by macrophages (ИЛ-1) and T cells (ИЛ-6), both cytokines can be synthesized by Neurons, glial cells, and cells within the pituitary and Adrenal Glands. This further highlights the crucial role of these cytokines as bidirectional mediators during the body's stress response.