Role of other systems and cells in allergy
Nonspecific allergy (nonspecific hypersensitivity and hyperreactivity) may occur due to the initial genetically and/or phenotypically altered reaction of various cells and humoral systems.
In allergic reactions, leukotrienes are involved. Under the influence of various pathogens on leukocytes, phospholipase A is activated, which involves in the metabolism arachidonic acid from phospholipids of cell membranes. The products of its metabolism – eicosanoids – are involved in the formation of leukotrienes andprostaglandins , inflammatory mediators that cause the development of hyperreactivity. LT-B4 is a strong chemoattractant for neutrophils and eosinophils, it stimulates inflammation, LT-C4 enhances edema and histamine release, prostaglandin PGD2 causes smooth muscle contraction.
Immunoneuroendocrine interactions determine overall body homeostasis and its reactivity. The cytokines of the immune system affect the functions of neurons, synapses, cells of the endocrine system. On the other hand, neurotransmitters and hormones alter the responses of the immune system.
Dysmetabolic – a dysregulatory nonspecific variant of allergy is characterized by the fact that with genetically determined metabolic abnormalities, pathogens and provoking factors induce the release of mediators and cytokines. The receptor-mediator imbalance in the regulation of the cumulative effects of the immune, nervous and endocrine systems on various impacts usually determines the development of nonspecific allergy.
An imbalance in the regulation of the nervous system can cause the occurrence of nonspecific allergy. The sympathetic nervous system through β-adrenergic receptors (β1 – constriction, β2 – dilatation), and the parasympathetic through M-cholinergic receptors (constriction) regulate smooth muscle tone and the release of mediators from cells. The predominance of the activity of the parasympathetic nervous system over the sympathetic, decrease in the activity and number of β2 receptors on the cells during stimulation by nonspecific agents leads to the predominance of M-cholinergic receptors and inflammatory mediators. The increased activity of non-cholinergic excitatory nerves causes the release of neuropeptides: vasoactive intestinal peptide (VIP) – substance P, neurokinin A, calcitonin gene-related peptide (CGRP), inducing edema, hypersecretion, bronchospasm, skin reactions.
Dysfunctions of the endocrine system (thyroid hormones, cortisol, estrogens, etc.) lead to a change in reactivity. Often there aredishormonal allergy variants caused by impairments in the relationship of the hypothalamus-pituitary-adrenal cortex, which leads to primary or secondary adrenal insufficiency and steroid dependence in the treatment of pathology, for example, bronchial asthma, chronic urticaria. In cases of impaired ovarian function and menstrual cycle, menopause, an imbalance of estrogen and progesterone develops, which is the cause of urticaria and asthma.
Any cells can participate in the development of allergy (Fig. 3).Nonspecific allergic reactions, apparently, can be triggered and carried out by those cells that have receptors that bind the pathogen, or signal structures that respond to the physical factor (light, cold). However, their response should be increased. Epithelial and endothelial cells, fibroblasts and other cells are capable of secreting cytokines, enzymes and other molecules under the influence of pathogens and, if their response is abnormal, increased, this can lead to the development of allergy (Fig. 2).
Epithelium stimulated by pathogens secretes IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). These cytokines mobilize the migration of dendritic cells to the lymph nodes, where they activate naïve T lymphocytes in Th2, which are involved in allergy.
Smooth muscle cells have receptors for mediators and cytokines of allergic reaction and their contraction is an important sign of allergic diseases (asthma, rhinitis, intestinal allergy).
Vascular endothelium responds to hypersensitivity mediators with an increase in permeability, which leads to edema, skin hyperemia, subendothelial leukocyte infiltration. Endothelial cells secrete a number of cytokines.
Fibroblasts, when activated by neurotransmitters and cytokines, secrete the precursors of collagen and elastin proteins, as well as mucopolysaccharides, and cytokines.
Therefore, allergy as pathologically altered reactivity may include immune and non-immune mechanisms.