Influenza: causes and pathogenesis

Causes of influenza

The cause of the flu is orthomixoviruses (the family Orthomyxoviridae) - RNA-containing complex viruses. They got their name because of the affinity for the mucoproteins of the affected cells and the ability to join the glycoproteins - the surface receptors of the cells. The family includes the genus Influenzavirus, which contains viruses of three serotypes: A, B and C.

The diameter of the virus particle is 80-120 nm. The virion is spherical (less often threadlike). In the center of the virion is nucleocapsid. The genome is represented by a single-stranded RNA molecule, which has 8 segments and 7 segments in Serotype C in serotypes A and B.

The capsid consists of the nucleoprotein (NP) and the proteins of the polymerase complex (P). Nucleocapsid is surrounded by a layer of matrix and membrane proteins (M). Outside these structures is located the outer lipoprotein membrane, carrying on its surface complex proteins (glycoproteins): hemagglutinin (H) and neuraminidase (N).

Thus, influenza viruses have internal and surface antigens. Internal antigens are represented by NP- and M-proteins; these are type-specific antigens. Antibodies to internal antigens do not have a significant protective effect. Surface antigens - hemagglutinin and neuraminidase - determine the subtype of the virus and induce the production of specific protective antibodies.

Serotype A viruses are characterized by a constant variability of surface antigens, and changes in H and N antigens occur independently of each other. There are 15 subtypes of hemagglutinin and 9 - neuraminidase. Viruses of serotype B are more stable (5 subtypes are distinguished). The antigenic structure of the viruses of serotype C is not subject to changes, neuraminidase is absent.

The extraordinary variability of serotype A viruses is due to two processes: antigenic drift (point mutations in genome sites that do not go beyond the strain) and a cipher (a complete change in the structure of the antigen with the formation of a new strain). The reason for the antigenic shift is the replacement of the whole RNA segment as a result of the exchange of genetic material between human and animal influenza viruses.

According to the modern classification of influenza viruses proposed by WHO in 1980, it is customary to describe the virus serotype, its origin, year of isolation and subtype of surface antigens. For example: the influenza A virus, Moscow / 10/99 / NZ N2.

Viruses of serotype A have the highest virulence and have the greatest epidemiological significance. They are isolated from humans, animals and birds. Viruses of serotype B are only isolated from humans: virulence and epidemiological significance are inferior to viruses of serotype A. Influenza viruses C low reproductive activity is inherent.

In the environment, the resistance of viruses is average. They are sensitive to high temperatures (more than 60 ° C), the effects of ultraviolet radiation and fat-soluble, but retain virulent properties for a time at low temperatures (they do not die at 40 ° C for a week). They are sensitive to table disinfectants.

[1], [2], [3],

The pathogenesis of influenza

The influenza virus has epitheliotropic properties. Getting into the body. It is reproduced in the cytoplasm of the cells of the cylindrical epithelium of the mucous membrane of the respiratory tract. Replication of the virus occurs quickly, within 4-6 hours, which explains the short incubation period. Affected by the influenza virus, cells degenerate, necrotic and are rejected. Infected cells begin to produce and release interferon, preventing further spread of the virus. Protection of the body from viruses is promoted by nonspecific thermolabile B-inhibitors and secretory antibodies of IgA class. Metaplasia of the cylindrical epithelium reduces its protective function. The pathological process covers tissues lining the mucous membranes and the vasculature. Epitheliotropy of the influenza virus is clinically expressed in the form of tracheitis, but the lesion can affect large bronchi, sometimes the larynx or pharynx. Already in the incubation period, viremia is manifested, lasting about 2 days. Clinical manifestations of viremia are toxic and toxic-allergic reactions. This effect has both viral particles and decay products of epithelial cells. Intoxication in influenza is due primarily to the accumulation of endogenous biologically active substances (prostaglandin E2, serotonin, histamine). The role of free oxygen radicals supporting the inflammatory process, lysosomal enzymes, as well as the proteolytic activity of viruses in the realization of their pathogenic action was established.

The main link of pathogenesis is the defeat of the circulatory system. The microvasculature vessels are more likely to change. Due to the toxic effect of the influenza virus and its components on the vascular wall, its permeability increases, which causes the hemorrhagic syndrome to appear in patients. Increased vascular permeability and increased "fragility" of the vessels lead to edema of the mucous membrane of the respiratory tract and lung tissue, multiple hemorrhages in the alveoli and interstitium of the lungs, and virtually all internal organs.

At an intoxication and caused by it disturbances of a pulmonary ventilation and a hypoxemia there is a disturbance of microcirculation: the speed of a vein-capillary blood flow slows down, the ability of erythrocytes and thrombocytes to aggregation increases, vascular permeability decreases, blood fibrinolytic activity decreases and viscosity of blood increases. All this can lead to disseminated intravascular coagulation - an important link in the pathogenesis of infectious-toxic shock. Disorders of hemodynamics, microcirculation and hypoxia contribute to the development of dystrophic changes in the myocardium.

Violation of blood circulation caused by vascular damage plays an important role in damage to the functions of the central nervous system and the autonomic nervous system. The effect of the virus on the vascular plexus receptors contributes to hypersecretion of the cerebrospinal fluid, intracranial hypertension, circulatory disorders, and cerebral edema. High vascularization in the hypothalamus and pituitary gland, performing neuro-vegetative. Neuroendocrine and neurohumoral regulation, causes the emergence of a complex of functional disorders of the nervous system. In the acute period of the disease there is sympathicotonia, leading to the development of hyperthermia, dryness and pallor of the skin, increased pulse, increased blood pressure. With a decrease in toxicosis, signs of parasympathetic excitation of the autonomic nervous system are noted: inhibition, drowsiness, a decrease in body temperature, a decrease in the pulse, a drop in blood pressure, muscle weakness, adynamia (asthenovegetative syndrome).

A significant role in the pathogenesis of influenza and its complications, as well as in the development of inflammatory changes in the respiratory tract belongs to the bacterial microflora, the activation of which contributes to epithelial damage and the development of immunosuppression. Allergic reactions in influenza arise on the antigens of both the virus itself and bacterial microflora, as well as the products of the disintegration of the affected cells.

The severity of the flu is partly due to the virulence of the influenza virus, but to a greater extent - the state of the immune system of the macroorganism.