The effects of stress on the immune system and the periodontal diseases
Georgios Alexandros Vakirtzian and Alexia Karamini
1) Nowadays, stress is defined as psychological and metabolic disorder, which can be caused by many aggressive factors and psycho-physiological reactions where an organism faces the idea of a challenge or a threat. Normally our body regulates itself in order to maintain it’s normal function through homeostatic mechanisms. Despite the fact that can be beneficial it keeps us in alertness. However, it can pose a threat on our homeostasis causing pain, discomfort and pathological conditions. Stressors interfere in our adaptability to cope with diseases, as well as, they push out of the limits the homeostatic mechanisms generating illnesses. The stress expression can be defined as the incompetence of person to face the requirements of an extremely difficult condition
2) Stress can endanger our organism when it lasts more than it can be tolerated or when some factors of neuroendocrine reaction act on systems which already present pathological liability. Studies indicate the association between a stressful life and the increased danger of various diseases including infectious diseases. However, individual differences in the way individuals perceive and cope with stressful events is as important as the stressors themselves in determining health or disease. The state of learned helplessness in animals is associated with reduced natural killer cell activity (NK cell) and increased metastasis of cancerous tumors, leading to reduced survival time.
3) Recent research has provided evidence that chemical messenger substances, released from nerve endings (neurotransmitters and neuropeptides), endocrine glands (hormones), and immune cells (cytokines and peptide hormones) and their receptors, constitute a biochemical information network between and within the immune and neuroendocrine systems. It has also been shown that products from the nervous and the neuroendocrine systems, released by emotional stress, may influence immune activities and the outcome of diseases, including infectious diseases.
4) Physiological responses to emotional stressors have been shown to modulate the immune system through the neural and endocrine systems in at least three different ways:
- – through the autonomic nervous system pathways
- – through the release of hypothalamic and pituitary hormones
- – through the release of neuropeptides
To begin with, emotional stress leads to secretion of noradrenaline from sympathetic neural fibers of autonomic nervous system and participates in the hormonal secretion of noradrenaline, as well as the adrenaline derives from the cells of adrenal medulla. Adrenaline and noradrenaline result in cardiovascular and metabolic disorders, in interaction with adrenergic receptors. In addition, the sympathetic nervous system moderates the immune cells activities.
The noradrenergic nervous fibers are located on immune system tissues and participate in the release of noradrenaline. Noradrenaline takes part in immune system reactions. The adrenergic stimulation brings on the differentiation and the maturation of T- leucocytes, the development of cytotoxic T – leucocytes and the production of antibodies from the plasma cells. In addition the hormones from hypophysis, hypothalamus and the adrenal medulla influence the immune system.
During the immune response the higher brain centers of central nervous system cause the release of corticotropin – releasing factor ( CRF) and system arginine – vasopressin (AVP) from the hypothalamus. CRF acts alone or with the AVP when hypophysis is activated. Also CRF releases the ACTH hormone in the blood circulation then ACTH acts on adrenal cortex and that has as result the production and the deliverance of glucocorticoid hormones. The effects of GCs on the immune system are biphasic. An emotional stress stimulus will result in an initial inhibition of macrophages and T-cell development, but the prolonged release of GCs may stimulate the immune response. The clinical effects of GCs after a stress response are a decrease in the number of lymphocytes in the peripheral blood and a large increase in the number of neutrophilic granulocytes . The main function of GCs seems to suppress the acute stress response, including the immune response once it has been elicited. CRF stimulates the production of signal substances from immune cells (cytokines), such as interleukin-1 (IL-1) by monocytes. It increases the proliferation of T-cells, stimulates the release of IL-2, and promotes the upregulation of IL-2 receptors on helper T- cells. ACTH inhibits the production of gamma-interferon (IFN-γ) by T-cells and inhibits the expression of IFN-γ receptors on macrophages, thus blocking the activation of macrophages by this cytokine. ACTH also promotes B- cell proliferation, but inhibits antibody production.
Neuropeptides released from peptidergic nerve fibers also modulate the activity of the immune system and the release of cytokines. This includes SP, somatostatin, the endogenous opioid peptides (beta endorphin and enkephalins), VIP and nerve growth factor. Among these the neuropeptide SP, secreted from sensory C-type nerve fibers, may be of particular interest for immune reactions in the gingiva and the periodontium when triggered by dental plaque bacteria
5) The relationship between stress and periodontal disease can be manifested through the following mechanisms:
- The biological mechanisms: in which the stress may affect the tissues
- The behavioral changes: Stress can innovate bad habits in our life like smoking, bad oral hygiene that they may influence advisedly the periodontal health
Stress affects the hormonal function through hypothalamic- pituitary axis that has as result the stimulation of anterior pituitary (adenohypophysis), which causes secretion of corticosteroid from adrenal cortex. If the causative agent doesn’t dissociate the fatigue will continue and that will cause tissues damage. One of the most important consequences of corticosteroid secretion (especially of cortisol) is the modification of immune system’s action · cortisol suppress important processes of leucocytes , such as the presentation of antigens, differentiation of B-leucocytes to plasmocytes, chemo-taxis, the phagocytic ability of polymorph-nuclear leucocyte and the production of slgA and IgG.
Additionally stress stimulates the autonomic nervous system through hypothalamic- pituitary axis, that has as result the secretion of catecholamines (epinephrine, norepinephrine) from the adrenal medulla. Catecholamines participate in pathogenicity of periodontal diseases, influencing the production of prostaglandin and other inflammation moderators.
6) The gingiva and the periodontium are protected against inflammation in several ways. The secretory immunoglobulin A (SIgA) antibody is the most important in saliva as well as it may be the dominant antimicrobial factor in a healthy oral cavity. Studies have showed that the emotional stress may affect the secretion ability of immune system and the production of (SIgA), so the stress can affect the host defense of bacteria.
The immunological response maybe causes local destruction on the gum tissues, through cytokines. The cytokines stimulate mast cells and the fibroblast and those they can produce matrix metalloproteinases (MMPs). In addition (MMPs) can decompose extracellular matrix of connective tissue. The immune response does not operate autonomously, but in close cooperation with the nervous and neuroendocrine systems. When the body is in an acute stress or alarm state, there is a marked increase of immune cells in the plasma, the circulating concentration of T-helper leucocytes, cytotoxic T – leucocytes, NK and the levels of IgM , IgG also increase.
Psycho-immunological studies show that after stress presence there is repression in production of interleukin 2 and on T – leucocytes that mediate at immune and NK cells processes.
7) Stress is the most important predisposing factor at acute necrotizing ulcerative gingivitis. On the other hand, there are few studies that show us positive correlation between periodontal diseases and negative life events. Also, epidemiologic research on teams such as students or soldiers show that the appearance of this periodontal disease form is favored by situations like exams or great psychological and physical swallowing. This inflammation of gums is characterized by the necrosis of interdental papillae, bleeding, gum pain, the creation of false membrane and oral malodor. So psychophysical factors take an excellent place in pathophysiology of Acute necrotizing ulcerative gingivitis (ANUG). These factors leading in the decrease of oral hygiene, poor nutrition , increase smoking, and decline of immune system defense.
Although one important correlation pathogenetic mechanism between stress and (ANUG) is the activation of mechanisms that the act through autonomic nervous system and the neuroendocrine glands. Previous mechanisms leading in more secretion of corticosteroid and catecholamine. These have as result the decreasing of vascular microcirculation gum, saliva secretion, activity of polymorph nuclear neutrophil leucocytes and in the creation of the appropriate substrate nutrition for Prevotella Intemedia. All of them make easier the bacteria colonization of gum΄s tissues, that leads at destruction and necrosis of them.
Conclusively not only bacteria antigens, but also exterior stimulations can produce emotional and stressful reactions that they influence and modulate the immune system through nervous and neuroendocrine systems. The important issue is no longer whether the psyche influences immune cell activities, but rather how the interaction between nerve and hormonal stimulations regulates the immune cells within the tissue at cellular and molecular levels, and how this may influence the development and progression of chronic infections such as gingivitis and periodontitis. In humans, periodontal infections may act as models to study these psychosomatic interactions and the effects upon chronic inflammations in general.
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