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.