Respiratory Infections and Host-Pathogen Dynamics

Host and Pathogen Interactions in the Lungs

• Viral infections damage respiratory epithelium, impairing the mucociliary escalator and immune responses, increasing secondary bacterial infection risk.
• Strong respiratory defenses, such as immune response and mucociliary clearance, are crucial host factors influencing infection outcomes.
• Pathogen factors, including organism count, virulence, and host adaptation, significantly affect disease severity and infection likelihood.

Viral Infections and Respiratory Dysfunction

• Viral infections directly damage airway epithelial cells, compromising barrier integrity and exposing tissues to pathogens.
• The mucociliary escalator traps and removes pathogens; viral infections can alter mucus properties and damage cilia, reducing pathogen clearance.
• Viral infections can diminish macrophage numbers and impair their functions, facilitating bacterial colonization.
• Some viruses infect macrophages, triggering responses that further decrease immune effectiveness and risk of secondary infections.
• Changes in mucus production due to viral infections can lead to thicker mucus, trapping pathogens and promoting bacterial growth.

Immune Defenses of the Respiratory System

• Major defenses include physical barriers (coughing, sneezing), immune cells (neutrophils, macrophages), and soluble components like immunoglobulins.
• Factors such as age, nutrition, and immune status significantly influence susceptibility to respiratory infections.
• Stress can suppress immune responses through corticosteroid release, increasing vulnerability to infections.

Bronchus-Associated Lymphoid Tissue (BALT)

• BALT is located at airway bifurcations, mediating immune surveillance by transporting antigens to lymphoid follicles.
• Size of BALT increases during chronic respiratory infections due to lymphoid tissue hyperplasia.
• Variations in BALT presence exist among species, with humans having less compared to other mammals, birds, and reptiles.

Secretory IgA (sIgA) Characteristics and Functions

• sIgA is produced by plasma cells in BALT, consisting of two IgA molecules linked by a J-chain and protected by a secretory piece.
• It neutralizes viruses, prevents bacterial adhesion, and promotes bacterial agglutination for efficient clearance.
• Predominantly found in the nasal mucosa and upper respiratory tract, sIgA acts as a first line of defense against inhaled pathogens.
• Unique among immunoglobulins, sIgA can be secreted across epithelial barriers, contrasting with IgG and IgE.

Airway Epithelial Injury and Repair

• Airway injury often starts with ciliated cell damage, leading to cell death and denuded areas.
• Repair involves migration of healthy cells to cover exposed areas, followed by proliferation into ciliated and goblet cells.
• Goblet cell hyperplasia increases mucus production, providing some protection but potentially causing obstruction.
• Chronic injury can lead to metaplasia, compromising mucociliary clearance, and fibrosis in severe cases.

Bronchiectasis Explanation

• Characterized by abnormal dilation of the bronchi, typically due to chronic inflammation and infection.
• Structural changes include destruction of bronchial wall elements, resulting in weakened walls filled with pus.
• Clinical manifestations include chronic cough, purulent sputum, and recurrent infections.

Pneumonia vs. Acute Lung Injury (ALI)

• Pneumonia arises from infectious agents causing alveolar inflammation and consolidation, while ALI stems from non-infectious factors like sepsis.
• ALI leads to widespread alveolar damage and edema without the specific changes seen in pneumonia.
• Healing in pneumonia restores alveolar structure; ALI healing often results in fibrosis due to extensive damage.

Pulmonary Fibrosis Development

• Caused by chronic lung injury, leading to excessive collagen deposition by activated fibroblasts.
• Contributing factors include chronic inflammation and exposure to toxins.
• Key cells involved: fibroblasts, myofibroblasts, and Type II alveolar cells.
• Physiological changes include reduced lung compliance, impaired gas exchange, and restrictive disease due to thickened alveolar walls.### Restrictive Lung Disease and Pulmonary Fibrosis
• Restrictive lung disease is marked by challenges in lung expansion and oxygen absorption.
• Pulmonary fibrosis causes restrictive lung disease through thickening of alveolar walls due to excessive collagen.
• The thickened lung tissue reduces elasticity, complicating lung inflation, leading to lower lung volumes and impaired gas exchange.
• Pulmonary fibrosis is largely considered irreversible, as collagen deposition and tissue scarring create permanent changes.
• Treatment aims to slow progression and manage symptoms rather than reverse the condition.

Alveolar vs. Interstitial Emphysema

• Alveolar emphysema involves abnormal enlargement of air spaces beyond terminal bronchioles due to alveolar wall destruction.
• Microscopically, alveolar emphysema displays large, irregularly shaped alveoli with loss of septa, disrupting the capillary network and reducing gas exchange efficiency.
• Interstitial emphysema is characterized by air trapped in connective tissue due to alveolar rupture, often resulting from trauma or overinflation.
• Microscopic appearance can show air-filled spaces in interstitial tissue without significant alveolar wall destruction.

Mechanisms of Obstructive vs. Restrictive Diseases

• Obstructive lung diseases are defined by airway obstruction leading to airflow limitation, examples include asthma, chronic bronchitis, and emphysema.
• Restrictive lung diseases are characterized by reduced lung expansion due to stiffness or fibrosis, with examples including pulmonary fibrosis, asbestosis, and sarcoidosis.
• The primary difference lies in obstructive diseases causing airflow obstruction, while restrictive diseases result in reduced lung volumes.

Clinical and Microscopic Distinctions

• Alveolar emphysema is clinically more significant due to its severe effects on gas exchange and lung function, leading to notable symptoms like dyspnea.
• Interstitial emphysema is usually less symptomatic but can complicate other pulmonary conditions if severe.
• In obstructive diseases, pulmonary function tests indicate reduced FEV1 and a decreased FEV1/FVC ratio, while restrictive diseases show reduced total lung capacity and normal/increased FEV1/FVC ratio.

Management Approaches

• Management of obstructive diseases focuses on easing airway obstruction with bronchodilators, corticosteroids, and mucolytics.
• Restrictive disease management centers on reducing inflammation or fibrosis, often employing corticosteroids, immunosuppressants, and pulmonary rehabilitation efforts.

Major Host Defenses in the Respiratory System

• Defense mechanisms include physical actions like coughing and sneezing.
• The mucociliary escalator helps trap and expel pathogens.
• Immune cells involved are neutrophils and macrophages.
• Soluble mucus contains immunoglobulins, lysozyme, and complement proteins.
• These defenses collectively prevent pathogen colonization and infection.

Influence of Factors on Respiratory Infections

• Age impacts immune function; young and elderly are more susceptible.
• Nutritional status affects immune response durability.
• Immune status, particularly in immunocompromised individuals, lowers defense against pathogens.

Role of Stress in Host-Pathogen Interactions

• Stress triggers corticosteroid release, which suppresses immune function.
• Reduced immunity increases vulnerability to respiratory infections.

Pathogen Quantity and Infection Likelihood

• Higher pathogen counts can overwhelm respiratory defenses, enhancing infection risk.
• Crowded environments and deep inhalation increase pathogen exposure.

Pathogen Virulence Factors

• Virulence factors enable pathogens to adhere to and penetrate host tissues.
• These traits enhance the pathogen’s ability to cause infections, increasing severity.

Host-Adapted Pathogens

• Host-adapted pathogens evolve to infect specific species effectively.
• They can evade host defenses, leading to increased infection likelihood and severity.

Bronchus-Associated Lymphoid Tissue (BALT)

• Located at airway bifurcations and within airway connective tissue.
• Functions in immune surveillance and transports antigens to lymphoid follicles.
• Size increases with chronic respiratory infections due to lymphoid hyperplasia.

Secretory IgA (sIgA) Features

• Synthesized by plasma cells in the submucosa; transported through epithelial cells.
• Composed of a dimer linked by a J-chain, with a protective secretory piece.
• Functions to neutralize pathogens, prevent attachment, and facilitate bacterial agglutination.

Injury and Repair in Airway Epithelium and Alveolar Walls

• Airway injury begins with ciliated cell damage, leading to necrosis and repair via migration and proliferation of healthy cells.
• Alveolar injury damages Type I epithelial cells; repair involves Type II cell proliferation and differentiation, with potential progression to fibrosis.

Bronchiectasis

• Defined as irreversible dilation of bronchi, often due to chronic infection and inflammation.
• Results from destruction of bronchial wall components, leading to purulent material accumulation and infection cycles.

Comparison of Pneumonia and Acute Lung Injury (ALI)

• Pneumonia is caused by infections, leading to alveolar consolidation; acute lung injury stems from non-infectious factors, resulting in widespread damage.
• Healing mechanisms differ: pneumonia may clear exudate; ALI often results in fibrosis due to extensive tissue damage.

Pulmonary Fibrosis

• Develops from chronic injury leading to excessive collagen deposition by fibroblasts.
• Common causes include chronic inflammation, toxic exposure, and autoimmune disorders.
• Results in decreased lung compliance, impaired gas exchange, and restrictive lung disease.

Differences Between Obstructive and Restrictive Diseases

• Obstructive diseases are marked by airflow limitation (e.g., asthma, chronic bronchitis).
• Restrictive diseases feature reduced lung expansion due to tissue stiffness (e.g., pulmonary fibrosis).
• Obstructive disorders hinder exhalation while restrictive disorders limit inhalation.

Alveolar Emphysema Development and Microscopic Appearance

• Characterized by enlarged air spaces due to alveolar wall destruction from chronic irritants.
• Microscopically reveals large, irregular alveoli with loss of septa.### Alveolar and Interstitial Emphysema
• Alveolar spaces can become expanded, causing disruption in the capillary network and resulting in decreased perfusion and gas exchange efficiency.
• Interstitial emphysema is characterized by air accumulation in the lung connective tissue septa due to alveolar rupture.
• Causes of interstitial emphysema include forceful coughing, overinflation of the lungs, or physical trauma that allows air to escape from alveoli into interstitial tissues.
• Microscopic examination reveals air-filled spaces within interstitial connective tissue without significant destruction of alveolar walls; air may dissect through septa and accumulate beneath the pleura.
• Alveolar emphysema notably impacts gas exchange and lung function, presenting with symptoms such as shortness of breath and reduced exercise tolerance, while interstitial emphysema tends to be less symptomatic but may complicate other lung conditions.

Mechanisms of Lung Disease

• The primary mechanism of obstructive lung disease involves limited airflow due to airway narrowing or blockage, caused by conditions like asthma (bronchoconstriction), chronic bronchitis (inflammation and mucus), or emphysema (loss of elastic recoil).
• Air trapping occurs in obstructive diseases, leading to lung hyperinflation as patients find it difficult to completely exhale.
• Examples of obstructive lung diseases include asthma (reversible airway constriction), chronic bronchitis (persistent airway obstruction), and emphysema (destruction of alveolar walls).
• Restrictive lung disease primarily results from reduced lung expansion due to parenchymal stiffness or fibrosis, which limits lung inflation and decreases compliance during inspiration.
• Examples of restrictive lung diseases include pulmonary fibrosis, asbestosis, and sarcoidosis, all causing scarring that leads to reduced lung volumes and impaired gas exchange.

Pulmonary Function Tests (PFTs) and Management

• PFTs in obstructive lung diseases typically show decreased forced expiratory volume in one second (FEV1) and a low FEV1/FVC ratio, indicating airflow limitation.
• In restrictive lung diseases, PFTs reveal reduced total lung capacity (TLC) with decreased lung volumes, but normal or increased FEV1/FVC ratio, showing reduced lung expansion efficiency.
• Management strategies for obstructive lung diseases emphasize relieving airway obstruction and improving airflow with bronchodilators, corticosteroids, and mucolytics.
• Approaches for restrictive lung diseases focus on decreasing inflammation or fibrosis, typically with corticosteroids, immunosuppressive agents, and pulmonary rehabilitation to enhance lung function and quality of life.

Alveolar Vulnerability

• The alveolar region has a large surface area and thin tissue barrier essential for gas exchange but also increases susceptibility to toxic and infectious agents.

Respiratory Microbiome Composition

• Composition is influenced by microbial immigration, elimination, and reproduction rates.
• Healthy balance is disrupted during respiratory disease, leading to overgrowth of pathogenic organisms.

Defense Mechanisms in the Respiratory System

• Primary defenses include:
  • Cough/sneeze reflex
  • Mucociliary escalator
  • Neutrophils and macrophages
  • Immunoglobulins/complement
  • Overall immune response.

Factors Influencing Pulmonary Infection

• Determined by:
  • Number of inhaled organisms
  • Pathogen virulence, including survival and replication capabilities
  • Adaptation of pathogens to host conditions.

Mucociliary Clearance

• Mucociliary escalator removes particles by transporting mucus, which traps pathogens, upward to the pharynx.

Impairment of Mucociliary Clearance

• Can be impaired by:
  • Atropine administration
  • Airway injury, suction, or bronchoscopy
  • Prolonged coughing
  • Chemical pollutants and viral/bacterial infections.

Role of Alveolar Macrophages

• Engulf foreign debris, bacteria, and viruses.
• Can exit alveoli via the mucociliary escalator or migrate into lymphatic vessels.

Pulmonary Intravascular Macrophages

• Located in pulmonary capillaries, engulf circulating particles, and can trigger inflammatory responses upon encountering pathogens.

Recruitment of Neutrophils

• Alveolar macrophages secrete chemotactic mediators after engulfing bacteria, aiding neutrophil migration to the alveolar space.

Pulmonary Immune Response

• Dendritic cells sample airborne antigens and present them to T and B cells for an immune response, impacting bronchial mucosa.

Bronchus-Associated Lymphoid Tissue (BALT)

• BALT consists of lymphocyte nodules crucial for initiating immune responses to inhaled antigens.

Role of M Cells in BALT

• Specialized epithelial cells that transport antigens from airways to lymphocytes, enhancing immune response.

Structure and Function of Immunoglobulin A (IgA)

• IgA is a dimer linked by a J-chain, secreted into the airway lumen, and is vital for mucosal immunity by neutralizing and agglutinating pathogens.

Other Antibodies

• IgG is important for opsonization of bacteria, while IgE binds to mast cells to mediate degranulation and inflammation.

Viral Infections and Epithelial Damage

• Can destroy epithelial cells or cause cilia dysfunction, impairing mucociliary clearance and respiratory defenses.

Consequences of Viral-Induced Injury

• Epithelial damage leads to inflammatory cell accumulation and increased susceptibility to secondary infections.

Pathogen Attachment Mechanisms

• Virus particles attach to cilia, damaging them and compromising mucociliary clearance, increasing risks for other infections.

Immune Response Impact on Bacterial Defense

• Viral infections can temporarily weaken antibacterial activities, increasing the risk of subsequent bacterial pneumonia.

Stress and Mannheimia hemolytica in Cattle

• Transport stress significantly raises prevalence in cattle, leading to increased risks for bovine pneumonic pasteurellosis.

Mycoplasma Effects

• Causes structural alterations in respiratory cilia, impairing function and decreasing clearance, predisposing to secondary infections.

Bacterial Attachment Consequences

• Bordatella bronchiseptica attachment disrupts ciliary function, preventing effective mucociliary clearance and promoting infections.

Epithelial Injury Consequences

• Results in cilia loss, increased mucus production, and inflammatory cell recruitment, leading to respiratory function impairment and chronic conditions.

Goblet Cell Hyperplasia

• Increased goblet cells in response to airway irritation leads to excess mucus, which may protect but also obstruct airways and hinder clearance.

Features of Purulent Bronchitis

• Characterized by airways filled with neutrophils and mucus due to chronic infection, potentially leading to airway obstruction.

Airway Epithelial Repair

• Basal cells proliferate and migrate to replace damaged epithelial cells, restoring airway surface integrity.

Mechanisms of Airway Obstruction in Chronic Bronchitis

• Caused by mucus accumulation or airway wall thickening due to chronic inflammation and inability to clear irritants.

Bronchiectasis Development

• Chronic infection leads to airway wall damage, resulting in structural distortion and accumulation of purulent debris.

Emphysema Mechanisms

• Chronic inflammation from smoking activates neutrophils that degrade collagen and elastin, causing obstructive disease.

Airway Smooth Muscle in Asthma

• Smooth muscle constriction during asthma reduces airway lumen size, contributing to airflow limitation alongside mucus and inflammation.

Comparison of Asthma and Chronic Bronchitis

• Asthma features reversible bronchospasm without wall thickening, while chronic bronchitis is marked by persistent inflammation and irreversible airway obstruction.

Particle Size and Respiratory Deposition

• Large particles (>5 µm) are trapped in upper airways, medium particles (1-5 µm) settle in smaller airways, and fine particles (<1 µm) can reach the alveoli.

Alveolar Vulnerability

• The alveolar region has a large surface area and thin tissue barrier essential for gas exchange but also increases susceptibility to toxic and infectious agents.

Respiratory Microbiome Composition

• Composition is influenced by microbial immigration, elimination, and reproduction rates.
• Healthy balance is disrupted during respiratory disease, leading to overgrowth of pathogenic organisms.

Defense Mechanisms in the Respiratory System

• Primary defenses include:
  • Cough/sneeze reflex
  • Mucociliary escalator
  • Neutrophils and macrophages
  • Immunoglobulins/complement
  • Overall immune response.

Factors Influencing Pulmonary Infection

• Determined by:
  • Number of inhaled organisms
  • Pathogen virulence, including survival and replication capabilities
  • Adaptation of pathogens to host conditions.

Mucociliary Clearance

• Mucociliary escalator removes particles by transporting mucus, which traps pathogens, upward to the pharynx.

Impairment of Mucociliary Clearance

• Can be impaired by:
  • Atropine administration
  • Airway injury, suction, or bronchoscopy
  • Prolonged coughing
  • Chemical pollutants and viral/bacterial infections.

Role of Alveolar Macrophages

• Engulf foreign debris, bacteria, and viruses.
• Can exit alveoli via the mucociliary escalator or migrate into lymphatic vessels.

Pulmonary Intravascular Macrophages

• Located in pulmonary capillaries, engulf circulating particles, and can trigger inflammatory responses upon encountering pathogens.

Recruitment of Neutrophils

• Alveolar macrophages secrete chemotactic mediators after engulfing bacteria, aiding neutrophil migration to the alveolar space.

Pulmonary Immune Response

• Dendritic cells sample airborne antigens and present them to T and B cells for an immune response, impacting bronchial mucosa.

Bronchus-Associated Lymphoid Tissue (BALT)

• BALT consists of lymphocyte nodules crucial for initiating immune responses to inhaled antigens.

Role of M Cells in BALT

• Specialized epithelial cells that transport antigens from airways to lymphocytes, enhancing immune response.

Structure and Function of Immunoglobulin A (IgA)

• IgA is a dimer linked by a J-chain, secreted into the airway lumen, and is vital for mucosal immunity by neutralizing and agglutinating pathogens.

Other Antibodies

• IgG is important for opsonization of bacteria, while IgE binds to mast cells to mediate degranulation and inflammation.

Viral Infections and Epithelial Damage

• Can destroy epithelial cells or cause cilia dysfunction, impairing mucociliary clearance and respiratory defenses.

Consequences of Viral-Induced Injury

• Epithelial damage leads to inflammatory cell accumulation and increased susceptibility to secondary infections.

Pathogen Attachment Mechanisms

• Virus particles attach to cilia, damaging them and compromising mucociliary clearance, increasing risks for other infections.

Immune Response Impact on Bacterial Defense

• Viral infections can temporarily weaken antibacterial activities, increasing the risk of subsequent bacterial pneumonia.

Stress and Mannheimia hemolytica in Cattle

• Transport stress significantly raises prevalence in cattle, leading to increased risks for bovine pneumonic pasteurellosis.

Mycoplasma Effects

• Causes structural alterations in respiratory cilia, impairing function and decreasing clearance, predisposing to secondary infections.

Bacterial Attachment Consequences

• Bordatella bronchiseptica attachment disrupts ciliary function, preventing effective mucociliary clearance and promoting infections.

Epithelial Injury Consequences

• Results in cilia loss, increased mucus production, and inflammatory cell recruitment, leading to respiratory function impairment and chronic conditions.

Goblet Cell Hyperplasia

• Increased goblet cells in response to airway irritation leads to excess mucus, which may protect but also obstruct airways and hinder clearance.

Features of Purulent Bronchitis

• Characterized by airways filled with neutrophils and mucus due to chronic infection, potentially leading to airway obstruction.

Airway Epithelial Repair

• Basal cells proliferate and migrate to replace damaged epithelial cells, restoring airway surface integrity.

Mechanisms of Airway Obstruction in Chronic Bronchitis

• Caused by mucus accumulation or airway wall thickening due to chronic inflammation and inability to clear irritants.

Bronchiectasis Development

• Chronic infection leads to airway wall damage, resulting in structural distortion and accumulation of purulent debris.

Emphysema Mechanisms

• Chronic inflammation from smoking activates neutrophils that degrade collagen and elastin, causing obstructive disease.

Airway Smooth Muscle in Asthma

• Smooth muscle constriction during asthma reduces airway lumen size, contributing to airflow limitation alongside mucus and inflammation.

Comparison of Asthma and Chronic Bronchitis

• Asthma features reversible bronchospasm without wall thickening, while chronic bronchitis is marked by persistent inflammation and irreversible airway obstruction.

Particle Size and Respiratory Deposition

• Large particles (>5 µm) are trapped in upper airways, medium particles (1-5 µm) settle in smaller airways, and fine particles (<1 µm) can reach the alveoli.

Influence of Particle Size on Respiratory Deposition

• Large particles greater than 5 µm are primarily deposited in the upper airways, such as the nose and throat.
• Medium-sized particles, ranging from 1 to 5 µm, settle in the smaller airways; deposition occurs as airflow slows down in these narrower passages.
• Small particles smaller than 1 µm can penetrate deeper into the respiratory tract, potentially reaching the alveolar regions where gas exchange occurs.

Pulmonary Silicosis

• Develops from inhaling silica particles, which are engulfed by alveolar macrophages but resist breakdown.
• Leads to macrophage death, attracting neutrophils and causing chronic inflammation.
• Results in lung tissue fibrosis, increasing lung density and reducing compliance.

Effects of Asbestos Fibers

• Asbestos fibers are challenging for macrophages to degrade, resulting in persistent tissue damage.
• Causes chronic inflammation and fibrosis, leading to asbestosis, a restrictive lung disease.
• Characterized by decreased lung compliance and impaired gas exchange.

Pulmonary Hypertension

• Defined as elevated blood pressure in the pulmonary arteries.
• Can originate from chronic hypoxia, lung diseases, or heart failure.
• Associated with the proliferation of vascular smooth muscle around pulmonary arterioles, increasing vascular resistance and pressure.

Characteristics of Pulmonary Emphysema

• Marked by the loss of collagen and elastin in lung tissue, leading to large air-filled spaces.
• Results in diminished structural support, elasticity, and elastic recoil of the lungs.
• Leads to hyperinflation, making it difficult to expel air, resulting in respiratory distress.

Impact of Alveolar Emphysema on Lung Function

• Causes destruction of alveolar walls, reducing the surface area available for gas exchange.
• Loss of lung elasticity hinders ventilation and exhalation.
• Contributes to symptoms associated with chronic obstructive pulmonary disease (COPD).