CH 21 - Respiratory Infections Flashcards
Antigenic drift
(definition)
Minor changes that occur naturally in influenza virus antigens as a result of mutation
Antigenic shift
(definition)
Major changes in the antigenic composition of influenza viruses that result from reassortment of viral RNA during infection of the same host cell by different viral strains
Granuloma
(definition)
Collections of lymphocytes & macrophages found in a chronic inflammatory response
An attempt by the body to wall off & contain persistent organisms & antigens
Mucociliary escalator
(definition)
Moving layers of mucus propelled by cilia lining the respiratory tract that traps bacteria & other particles & carries them toward the throat
Otitis media
(definition)
Inflammation of the middle ear
Pharyngitis
(definition)
Inflammation of the throat
Pneumonia
(definition)
Inflammation of the lungs accompanied by filling of the air sacs with fluids (ex: pus & blood)
Sputum
(definition)
Thick fluid containing mucus, pus, & other material coughed up from lungs
Normal flora:
Nose
Staphylococcus aureus
Normal flora:
Throat
Non-pathogens:
- S. viridans
- Neisseria species
- S. epidermidis
Throat flora INHIBITORY to (pathogens):
- Streptococcus pyogenes
- Neisseria meningitidis
- Staphylococcus aureus
Normal flora:
Mouth
Streptococcus viridans
- S. mutans in dental plaque (precursor to caries & perhaps endocarditis)
Anaerobic bacteria (gingival crevices):
1. Bacteroides
2. Fusobacterium
3. Clostridium
4. Peptostreptococcus
Actinomyces israelii
- Fungal organism (gingival crevices)
- Abscesses of jaw, lungs, or abdomen
Normal flora:
Lower respiratory tract & alveoli
Sterile
(little to no microbes)
Normal flora:
Conjunctiva
Commonly have no bacteria
- Invading organisms swept into tear ducts & nasal pharynx
Lower Respiratory Tract Infections
(listed)
- Influenza
- Pneumococcal pneumoniae
- Klebsiella pneumoniae
- Mycoplasmal pneumoniae
- Whooping cough
- Tuberculosis
- Legionnaires’ disease
- Respiratory syncytial virus infection
- Systemic mycoses
Influenza:
Causative agent
Influenza A virus
- Orthomyxovirus
- ssRNA genome (8 segments)
- Spiked envelope
H spike = hemagglutinin
- Aids in attachment
N spikes = neuraminidase
- Aids in viral spread (leaving cell)
Influenza:
Symptoms
Short incubation period (~2 days)
- Headache
- Fever
- Muscle pain
- Dry cough
Acute symptoms abate within 1 week
- Cough, fatigue, generalized weakness may linger
Influenza:
Pathogenesis
- Acquired through inhalation of respiratory secretions (aerosols)
- Attaches to host cell via hemagglutinin (H) spikes
- Envelope fuses with host membrane & replicates within cell - Mature virus buds from host cell
- Picks up viral envelope - Infected cells die/slough off
- Destroys mucociliary escalator - Host immunity quickly controls viral spread
Influenza:
Epidemiology
Outbreaks each year in US
- 10-40,000 deaths
Pandemics periodically
- 1918 = “Spanish flu”
- Higher than normal morbidity
Spread caused by major antigenic changes
Influenza:
Antigenic drift
Consists of minor mutations overtime
- Particularly hemagglutinin
Minimizes effectiveness of immunity to previous strains
- Enough susceptible people for continued viral spread)
Influenza:
Antigenic shift
More dramatic/sudden changes
Virus strains drastically antigenically different from previous
- Often more virulent
New virus comes from genetic reassortment
- 2 viruses infect cell at same time
- Genetic mixing results
Influenza:
Prevention
Vaccine 80-90% effective
New vaccine each year due to antigenic drift
Influenza:
Treatment
Antiviral medications: amantadine & rimantidine
- 70-80% effective
- MUST be taken early (not sub for vaccine)
- Inhibit uncoating of viral RNA in infected cells (prevents from leaving capsule)
Antineuraminidase: Tamiflu (Oseltamivir)
- Prevents virus from leaving cell to infect others
Pneumococcal pneumonia:
Causative agent
1 cause of bacterial pneumonia
Streptococcus pneumoniae
- G+
- Diplococci/short chains
- Thick polysaccharide capsule
- NO Lancefield grouping
- Known for producing hemolysin
- Primary virulent factor = capsule
- > 90 different types of S. pneumoniae based on capsular Ag
Nasopharyngeal colonizer
- Biofilm formation = immunoquiescent state (commensal)
- Growth requires convering sodium pyruvate into acetyl-phosphate (hydrogen peroxide byproduct inhibits growth of other colonizers - H. influenzae)
Pneumococcal pneumonia:
Symptoms
Cough
Fever
Chest pain
- Aggravated with cough/breathing
- Breathing becomes shallow/rapid
- Poor oxygenation (dusky skin, supplemental needed)
Sputum production
Runny nose & upper respiratory congestion
- Precedes above symptoms
Symptoms abate in individuals who survive 7-10 days without treatment
Pneumococcal pneumonia:
Epidemiology
30% carry encapsulated strain in throat (biofilm form)
Bacteria rarely reach lung due to mucociliary escalator
- Risk increases when escalator destroyed (ex: after flu)
Underlying disease & age increase risk of disease
Pneumococcal pneumonia:
Pathogenesis
Bacteria inhaled into alveoli
- Inflammatory response in lung
- Capsule interferes with phagocytosis
Pneumococci that enter bloodstream lead to 3 often fatal complications:
1. Septicemia (infection of bloodstream)
2. Endocarditis (infection of heart valves)
3. Meningitis (infection of membranes covering brain & spinal cord)
Recovery usually complete
- Most bacterial strains do NOT destroy lung tissue
Pneumococcal pneumonia:
Prevention
Polysaccharide vaccine
- Immunity to 23 strains (of pneumonia only)
- Does NOT work in children under 2yrs
Conjugate vaccine
- Against 13 types (in 2010; 7 types in 2000)
- Available for children
- Recently approved for adults
- Prevents colonization
Pneumococcal pneumonia:
Treatment
Antibiotics: penicillin & erythromycin
- Successful if given early
- More strains becoming antibiotic-resistant
Pneumococcal pneumonia:
Pore-forming toxins (PFTs)
Pneumolysin
- PFT of Streptococcus pneumonia
- High concentrations causes lysis (tissue damage)
- Lower concentrations causes ion dysregulation (pyroptosis or necroptosis)
Klebsiella pneumonia:
Causative agent
Several species of Klebsiella
Klebsiella pneumoniae = primary cause
- G- bacillus (LPS)
- Encapsulated (avoids phagocytosis, recognitions, & complement)
- ESKAPE pathogen
Klebsiella pneumonia:
Symptoms
Most symptoms indistinguishable from pneumococcal pneumonia
- Cough
- Fever
- Chest pain
Other symptoms:
- Repeated chills
- Red/gelatinous sputum (bloody/”currant-jelly”)
50-80% mortality in untreated pts
- Tend to die sooner than other pneumonia
Klebsiella pneumonia:
Epidemiology
Normal flora of intestine (GI) in small population
Colonization of mouth/throat more common in debilitated individuals
- Very young/old
- Alcoholics
- Institutional settings
Klebsiella pneumonia:
Pathogenesis
- Colonizes mouth & throat
- Carried to lung with inspired air/mucus
- Survival in lung aided by capsule
- Interferes with phagocytosis - Causes tissue death
- Necrosis & formation of lung abscesses = necrotizing pneumonia - Infection in bloodstream leads to abscesses in other tissues
- DIC
Klebsiella pneumonia:
Prevention & treatment
NO specific prevention measures
- Disinfect environment (medical equipment)
Use antimicrobials ONLY when necessary
- Help control resistance
Mycoplasmal pneumonia:
Causative agent
Mycoplasma pneumoniae
- Small (found in some cell lines)
- Deformed bacteria lacking cell wall
- Slow growing
- Aerobic
- Distinctive “fried egg” appearance
Mycoplasmal pneumonia:
Symptoms
Onset typically gradual
1st symptoms:
- Fever
- Headache
- Muscle pain
- Fatigue
Later symptoms:
- Dry cough (resembling “atypical pneumonia”
Usually no hospitalization required
- “Walking pneumonia”
Mycoplasmal pneumonia:
Epidemiology
Spread by aerosolized droplets from respiratory secretions
- Survive long periods in secretions (aids in transmission)
- Small infecting dose
~1/5 of bacterial pneumonias
Peak incidence in young people
Mycoplasmal pneumonia:
Pathogenesis
- Attaches to receptors on epithelium
- Interferes with ciliated cell action
- Ciliated cells slough off - Inflammation initiates thickening of bronchial & alveolar walls
- Difficulty breathing
Produces toxin (thought to be possible cause of asthma)
Mycoplasmal pneumonia:
Prevention & treatment
NO practical prevention
- Avoid crowding in schools & military facilities (particularly dorms/barracks)
Cell wall synthesis inhibitors = INEFFECTUAL
- Ex: penicillin
Antibiotics of choice: tetracycline & erythromycin
- Must be given early
- Bacteriostatic (inhibit growth, don’t kill)
Whooping cough:
Causative agent
Bordetella pertussis
- G- bacillus
- ONLY infects humans (particularly young children)
Whooping cough:
Symptoms
Mild upper respiratory infection
Followed by paroxysmal coughing
- Series of hacking coughs
- Accompanied by copious mucus production
- End with inspiratory “whoop” (air rushes past narrow glottis)
Whooping cough:
Epidemiology
Spreads via infected respiratory droplets
- Most infectious during runny nose period
- Number of organisms decrease with onset of cough
Primarily occurs in infants & young children
- Milder forms seen in older children/adults
Whooping cough:
Pathogenesis
- Enters respiratory tract via inspired air
- Attaches to ciliated cells via filamentous hemagglutinin (Fha) - Mucus secretion increases
- Ciliary action decreases while ciliated cells sloughed off
- Cough relex = only way to clear secretions - Produces numerous toxic products
- Pertussis toxin
- Adenylate cyclase toxin
- Tracheal toxin
Whooping cough:
Pertussis toxin
A-B toxin
B portion attaches to cell surface
A portion enters cell & inactivates cAMP regulation (overproduction)
- Increased mucus formation
- Inhibits many leukocyte functions (chemotaxis, phagocytosis, respiratory burst)
- Impairs NK cell killing
- Contributes to bacterial binding to ciliated epithelial cells
Whooping cough:
Adenylate cyclase toxin
Increased production of cAMP
Increased mucus formation
Decreased phagocytic & NK cell killing
Whooping cough:
Tracheal cytotoxin
Causes release of NO from goblet cells
- Death of ciliated epithelial cells
Release of IL-1
- Fever causing cytokine
Whooping cough:
Prevention
Vaccination of infants
- Preventions disease in 70% of individuals
- Injections given at 6 weeks & 4, 6, 18 months
DPT = combined with diphtheria & tetanus toxoids
Whooping cough:
Treatment
Erythromycin
- Reduces symptoms if given early
Antibiotic eliminates bacteria from respiratory secretions
- Little bearing on course of disease due to toxin productive
Supportive therapy
- O2 therapy
- Suction of mucus (especially infants)
Tuberculosis:
Causative agent
1 respiratory bacterial infection in world (affects 1/3 of population)
Mycobacterium tuberculosis
- G+ rod
- Obligate anaerobe
- Mycolic acid in cell wall (acid fast staining)
Slow growing
- Generation time = 12 hrs or more
Resists most methods of control
Tuberculosis:
Symptoms
Chronic illness
- Slight fever with night sweats
- Progressive weight loss
- Chronic productive cough
- Sputum often blood-streaked
Tuberculosis:
Pathogenesis
- Inhalation of airborne organisms
- Taken up by pulmonary macrophages in lungs - Resists destruction within phagocyte
- Prevents fusion of phagosome with lysosome
- Allows multiplication in protected vacuole - Activated macrophages can kill bacteria
- Intense immune reaction occurs ~ 2 weeks post infection
- Macrophages fuse & form multinucleated giant cells
- Granuloma (tubercle) forms when macrophages & lymphocytes surround large cell to wall off infected tissue - Lysis of activated macrophages release contents into infected tissue
- Death of tissue & formation of “cheesy” material - Granulomas can contain live organisms & lead to reactivation TB
