Viral entry and cellular tropism
Infection occurs via the aerosol mechanism. Having overcome non-specific defense factors (including mucociliary clearance and interferons), the virus reaches target cells.
Surface glycoprotein antigens play a key role in the entry process:
- Hemagglutinin (H) is responsible for attachment. It binds to specific receptors on the cell membrane — α-2', 6'-galactose-containing oligosaccharides.
- Neuraminidase (N) cleaves sialic acid, preparing receptors and facilitating the virion's movement through mucus. This enzyme also prevents newly formed viruses from clumping together upon exiting the cell.
Penetration into the epithelial cell occurs via receptor-mediated endocytosis. Genome replication (negative-sense RNA) takes place in the nucleus, while particle assembly occurs at the cell membrane.
Mechanisms of cytopathic action and inflammation
Influenza virus causes rapid death of infected cells. This occurs due to the complete depletion of cellular resources during replication and the direct induction of apoptosis by the viral protein PB1-F2. Massive epithelial cell death triggers a cascade of immune reactions.
Macrophages phagocytose destroyed cells, and mononuclear cells accumulate in the epithelium. A colossal amount of pro-inflammatory cytokines (interferons, interleukins, tumor necrosis factor) and other biologically active substances (histamine, serotonin, oxygen radicals) is released.
At the site of entry, serous-hemorrhagic inflammation develops:
- Blood vessels dilate (hyperemia occurs).
- Vascular permeability increases, leading to local edema.
- The sensitivity threshold of receptors in the areas of exposed submucosa decreases.
Clinical presentation
The incubation period lasts from 12 hours to 3 days, after which the disease rapidly progresses to the stage of full-blown clinical manifestations (up to 7 days).
Main syndromes:
- Respiratory syndrome: manifests with clinical features of acute laryngotracheobronchitis. A dry reflex cough, burning, and soreness behind the sternum occur.
- Intoxication syndrome: caused by massive viremia and the release of tissue breakdown products into the bloodstream. Characterized by fever, toxic encephalopathy, marked weakness, anorexia, and muscle pain (myalgia).
- Hemorrhagic syndrome: a consequence of vascular paresis and microcirculatory disorders. Manifests as epistaxis, petechial rash on the skin and mucous membranes.
Severe forms and complications
In severe influenza, metabolites dramatically increase the permeability of alveolocapillary membranes. Oncotic pressure in the lungs drops, fluid leaks into the interstitium, causing acute respiratory distress syndrome (ARDS) and hemorrhagic pulmonary edema.
Damage to type II alveolar epithelial cells leads to surfactant deficiency, alveolar collapse (atelectasis), and severe hypoxemia. Due to hypoxia and high vascular permeability, cerebral edema with intracranial hypertension (meningism) may develop.
Strains like the pandemic A/H1N1 swi pose a particular danger. They are capable of binding to α-2', 3' receptors in the terminal parts of the respiratory tract, causing primary severe viral pneumonia.
During the convalescence period, the risk of secondary bacterial superinfection persists due to the pronounced immunosuppressive effect of the virus.
Briefly: answers to topical questions
What is the fundamental difference between antigenic shift and antigenic drift of the influenza virus?
The fundamental difference lies in the mutation mechanisms and the scale of surface protein renewal.
| Characteristic | Antigenic drift | Antigenic shift |
|---|---|---|
| Mechanism of variability | Point mutations in the viral genome | Exchange of RNA segments (genetic reassortment) |
| Structural changes | Partial renewal of antigenic determinants | Complete replacement of hemagglutinin or neuraminidase |
| Epidemiological significance | Causes periodic epidemics every 2–3 years | Leads to pandemics due to a lack of population immunity |
Which drug classes are used for etiotropic therapy of influenza?
For etiotropic therapy of influenza, medications are conventionally divided into two groups.
1. Drugs with proven antiviral efficacy and a studied mechanism of action:
- Viral release inhibitor — oseltamivir.
- Endosomal viral release inhibitor — adamantanes, rimantadine.
- Viral entry inhibitor — umifenovir.
2. Drugs with antiviral effects based on a complex impact on the virus and the host's immune mechanisms:
- interferon-series drugs;
- endogenous interferon synthesis inducers.
Which extrapulmonary bacterial complications are most common in influenza?
The most frequent extrapulmonary bacterial complications of influenza are ENT infections, which rank second in frequency after bacterial pneumonias.
These include:
- sinusitis, including frontal sinusitis and maxillary sinusitis;
- otitis.
Additionally, among bacterial complications of influenza, sources note kidney damage — pyelitis and glomerulonephritis, central nervous system involvement — bacterial meningitis and meningoencephalitis, as well as septic conditions, including bacterial endocarditis and cryptogenic sepsis.
What are the clinical and laboratory criteria for severe influenza?
Clinical criteria for severe influenza:
- progressive worsening of the condition;
- hyperpyrexic fever;
- toxic encephalopathy with impaired consciousness;
- meningeal symptoms: increased headache, vomiting, hyperesthesia;
- signs of respiratory failure;
- cardiovascular collapse;
- worsening of hemorrhagic manifestations: epistaxis, skin hemorrhages, hemoptysis, risk of cavitary bleeding;
- focal changes in the lungs;
- signs of cardiovascular failure.
Laboratory and instrumental data used to assess severity and complications:
- in severe respiratory failure, hypoxemia may reach critical values: PaO2 less than 50 mmHg;
- chest X-ray may reveal bilateral confluent infiltrative opacities radiating from the lung roots.
Hemagglutinin (H) — "Grabs" the cell (ensures binding to the receptor). Neuraminidase (N) — "Chops" the mucus (cleaves sialic acid and releases the virion).
Class and exam questions
Why does the peak of influenza incidence occur in winter and spring?
During this period, the concentration of sialic acid, which is a natural inhibitor of viral neuraminidase, decreases in the respiratory secretions.
Which immune factors are the first to respond to virus penetration?
In the incubation period, non-specific defense mechanisms operate: infected cells and macrophages produce type 1 interferons ($\alpha$ and $\beta$), which protect neighboring cells and activate natural killer cells.
Why is there a high risk of bacterial superinfection in influenza?
Massive death and desquamation of the ciliated epithelium disrupt mucociliary clearance, and the preceding viral infection causes temporary immunosuppression, paving the way for opportunistic flora.
What else to study on this topic
- Mechanisms of viral variability: antigenic shift and drift.
- Features of antigenic structure and serotypes (types A, B, and C viruses).
- Principles of etiotropic and pathogenetic therapy for influenza.
- Virion morphology and genome: functions of internal proteins (NP, M).
- Specific and non-specific disease prevention.
Master the complete topic in the «Infectious Diseases» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Pathogenesis and Clinical Presentation of Influenza" and 3,312 more pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 41 video lessons on the subject
Other topics in the "Respiratory Infections" section
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.