Pulmonary defense

Question 1

What are the Upper respiratory host defenses?

Answer 1

– Anatomic barriers (epiglottis)

– Frequent branching of pulmonary tree • Aerodynamic filtration of inspired air

– Mucociliary clearance of particulates

– Cough Response

Question 2

what are lower respiratory tract defenses?

Answer 2

– Phospholipid surfactant

– Proteins (immunoglobulins, complement)

– Cellular defenses • Lymphocytes • Alveolar macrophages • Polymorphonuclear neutrophiles

Question 3

Explain the lung host defenses in the nasopharynx? What are the defects? What are the potential infection problems?

Answer 3

• Ciliated and squamous epithelium – Filtering system removes particles 10 mm or larger – Mucous layer with IgA, IgG to prevent epithelial attachment of bacteria
• Defects – Poor nutrition
• Potential infection problems

– Colonization with pathogenic GNB, Normal colonization is 2-6%, 4 days in ICU (40%), Colonization to infection (23%)

Question 4

Conducting Airways defenses?

Answer 4

• Mechanical barriers (larynx) and airway angulation
• Bronchoconstriction
• Mucociliary transport mechanisms – Tracheobronchial secretions – Cilia
• Local immunoglobulin coating – Secretory IgA major immunoglobulin upper airways – Prevent adherence and absorption – Antibody activity against viruses, bacteria, allergens

Question 5

Explain the defects and potential infection problems with Mechanical barriers in the conducting airways?

Answer 5

• Mechanical barriers (larynx) and airway angulation
• Defects – Endotrachael tube – Tracheostomy
• Potential infection problem – Aspiration • Direct entry of microorganisms into distal airway

Question 6

Explain the defects and potential infection problems with Bronchoconstriction?

Answer 6

• Bronchoconstriction
• Defects – Hyperactive airways – Intrinsic asthma
• Potential infection problem – Poor removal of secretions – Excessive thick secretions – Secondary infection

Question 7

Explain the defects and potential infections with Mucociliary transport mechanisms?

Answer 7

• Mucociliary transport mechanisms – Tracheobronchial secretions – Cilia
• Defects – Cilia toxic • Viruses, mycoplasma pneumonia – Intrinsic cilia defects • Chronic inflammation (smoking) • Kartagener syndrome

– Potential infection problem • Stagnant secretions • Bronchitis, bronchiectasis, sinusitis • Cystic fibrosis – Ciliatoxic factor secretions – Tenacious secretions – Infection (mucoid form pseudomonas)

Question 8

Explain the defects and potential infections with local immunoglobulin coating in the conducting airways?

Answer 8

• Local immunoglobulin coating – Secretory IgA major immunoglobulin upper airways – Prevent adherence and absorption – Antibody activity against viruses, bacteria, allergens
• Defects – IgA deficiency – Functional deficiency by bacterial breakdown (protease) • Sreptococcus pneumoniae, haemophilus influenza
• Potential infection problem – Sinopulmonary infection – Abnormal colonization with certain bacteria

Question 9

What are the special host defense mechanisms in the lungs?

Answer 9

1) . Surfactant
2) . • Antibody-Mediated Immunity
3) . • Immunoglobulins
4) . Complement
5) . Alveolar Machrophage

Question 10

What is surfactant secreted by what does it do? Potential defect? Potential infections problem?

Answer 10

Surfactant

– Secreted by type II pneumocytes – Antibacterial activity • Staph and GNB

– Potential defect • Decreased synthesis • Acute lung injury

– Potential infections problem • Loss of opsonization activity • Alveolar collapse (atelectasis)

Question 11

Explain uptake of antigen in the respiratory tract: conducting airways?

Answer 11

Conducting Airways

– Local defenses

– Mucosal defenses:

• Immunoglobulins • Local phagocytes • Into systemic circulation (blood, lymphatics) – Regional lymph nodes – RES system

– Peripheral Parenchyma (Alveoli) • Engulfed and processed by alveolar macrophages – Sent to T lymphocytes » Lymphokine production (enhance PMN, macrophages) » Direct cellular cytotoxicity

Question 12

Explain antibody mediated immunity specific mechanisms?

Answer 12

Antibody-Mediated Immunity

– Depends on B lymphocytes

– Recruits acute inflammatory cells

– Enhances phagocytosis

– Augments microbicidal activity

– Neutralizes toxins

– Inhibits microbial growth and adherence

– Activates complement cascade

Question 13

Explain the immunoglobulins in the lung?

Answer 13

– IgA • Neutralize reparatory viruses, exotoxins • Agglutinate microbial organism for mucociliary escalator • Prevent bacterial attachment to epithelial cells

– IgG and IgM • Most effective opsonizer (IgG) • Agglutinators of particulate antigens • Initiate complement cascade • Neutralize or lyse bacteria, viruses

– IgE • Host resistance to parasitic, viral infection

Question 14

Explain the complement in the lungs? potential defects? Potential infection problems?

Answer 14

Complement – Properdin Factor B • Direct lysis • Opsonization

– Defects •C 3 and C5 deficiency

– Potential infectious problem • Non life-threatening infection

Question 15

Explain the primary and secondary defenses of the alveolar macrophage?

Answer 15

• Primary Defense – Phagocytic against various antigens
• Secondary Defense

– Modulation of function of other inflammatory and immune responses • Presentation of processed antigen to T lymphocytes • Complement fragments • Chemotactic factors to PMN • Lymphocyte chemotaxin • Leukotrienes

Question 16

List intracellular bacteria that are contained in macrophages?

Answer 16

– Mycobacterium tuberculosis

– Mycobacterium lepraemurium

– Toxoplasma gondii

– Leishmania donovani

– Legionella pneumophilia

– Pneumocystis jiroveci

– Listeria monocytogenes

– Cytomegalovirus

– HIV

Question 17

List the role of the cell mediated immunity in the lungs?

Answer 17

Cell-Mediated Immunity – Depends on T lymphocytes – Recruits chronic inflammatory cells – Effects cytolysis of virally infected cells – Activates macrophages for enhanced intracellular killing – Induces granuloma formation

Question 18

What are the two major mechanisms of T cell functional activity?

Answer 18

– Two major mechanisms of T cell functional activity

• Lymphokine-mediated reactions
• Cell-mediated cytotoxicity – Cytolytic T effector cells (Neoplastic cells, viral infected cells) – Natural killer lymphocytes – Antibody-dependent cellular cytotoxicity (Macrophages binding to antibody-coated cells)

Question 19

What cytokines have a role in lung innate immunity?

Answer 19

– TNF-alpha

– IL 10, IL-12

– Chemokines

– Interferon-gamma

– G-CS

Question 20

expalin the role of IL-12 cytokines in the lung innate immune system?

Answer 20

IL-12

– Enhances CMI to intracellular pathogens

– Produced by AM, pulmonary epithelial cells, PMN

– Increased levels resulted in bacterial killing and improved survival

Question 21

Explain the role of TNF-alpha in the lung innate immune system?

Answer 21

TNF alpha

– LPS potent stimulus of TNF alpha

– TNF- stimulates AM to produce IFN -gamma to stimulate more cytokines

– Increase local levels in lung reduce bacterial counts and increase survival

– Increase systemically may worsen survival

Question 22

Role of IL-10 in the lung innate immune system?

Answer 22

IL 10

– Anti-inflammatory cytokine

– Down regulates production of TNF- , IFN-gamma, and chemokines

– Allows proliferation of bacteria

Question 23

Role of G-CSF?

Answer 23

G-CSF

– Maintain increase neutrophile delivery

– Increase neutrophile function

– Enhance clearance of bacteria and virulence faction

– Non-neutrophile mediated effects

– Antibiotic interactions • Increase levels of certain antibiotics into neutrophiles

Question 24

Explain Polymorphonuclear cells in the lung?

Answer 24

• Most numerous and important defense once fullblown inflammatory response occurs

– Sequestered in interstitial areas and capillaries

– Adherence to endothelium

– Chemotactic attraction to inflamed site

– Diapedesis into tissue

– Ingestion and destruction of microbes

Question 25

What are defects that occur in PMN's?

Answer 25

– Absolute deficiency – Decreased PMN adherence • Ethanol, steroids, anti-inflammatory agents – Decreased PMN chemotaxis • Deficiency of actin-myosin – Intrinsic defect • Unable to digest organisms • (chronic granulomatous disease)

Question 26

What is the normal amount of colonization in oral secretions?

Answer 26

* 10^7 organism/ml oral secretions – S. sanguis, S. mutans, S. salivarius, S. mitis * Oral mucosal colonization – Normal oral cell glycocalyx – Selective adherence of oral streptococci over GNB – Debilitated patients • Cell receptors change allowing GNB attachment and colonization

Question 27

What are determinants of bacterial clearance?

Answer 27

Inoculum Size – Important determinant of pathogenicity • 10 5 Pseudomonads cleared • 10 6 Pseudomonads resulted in multiplication in lung parenchyma – Phagocytic cell type vs. inoculum size • Small inocula of S. aureus (\<106) cleared by alveolar macrophages • Larger inocula require PMN Bacterial Virulence – Pathogenicity related to virulence factors – Virulence factors • Mucopolysaccharide capsule (Pneumococci, Haemophilus, K. pneumoniae) – Prevents phagocytosis in absence of effective opsonin – Extracellular products (Pseudomonas, S. aureus) • Extracellular enzymes, proteases (extensive destruction alveolar, bronchial, arterial walls with abscess formation) • Toxins • Antiopsonin factor (pneumococci)