Term
| Streptococcus pneumoniae: Virulence Factors |
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Definition
Polysaccharide capsule: primary VF
-Over 90 serotypes
-Anti-phagocytic
-Prevents complement deposition
-Evasion of lung surfactant
-Abs to it confer immunity
Pneumolysin: sulfhydryl activated cytolysin
-Damages membranes (like SLO)
-Binds cholesterol on cell membrane
-Acts on several cell types (PMN, monocytes, pulmonary epithelium)
-Several functions (immune evasion, spread to bloodstream, inflammation via complement activation)
Cell Wall TA/PG: inflammation
-Causes fever and lung damage
-Activate alternative complement pathway
-Production of IL1 and TNF |
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Term
| Streptococcus pneumoniae: Etiology |
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Definition
Human pathogen only: many asymptomatic carriers
Transmission: person to person (droplet)
Most common cause of acute bacterial pneumonia: in all age groups |
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Term
| Streptococcus pneumoniae: Pathogenesis |
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Definition
Organism establishes in LRT:
-Aspiration from middle RT
-Compromised cough reflex permits entry (stroke, alcoholism, viral infection, anesthesia)
-Alveolar Abs NORMAY clear it
Acute Pneumonia: infection of lung parenchyma
-Cough with productive sputum (purulent and rusty red color)
-Inflammation ↑ vascular permeability fluid accumulation suffocation
Secondary Complications:
-Bacteremia (due to inflammation and damage to endothelial cells)
-Acute Purulent Meningitis |
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Term
| Streptococcus pneumoniae: Clinical ID |
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Definition
Sputum Gram Stain: issue because of contamination with polymicrobic saliva
Blood Culture: detects bacteremia
-Latex agglutination for Abs
Radiology: bronchopneumonia or lobar consolidation
Shape: G(+) lancet shaped diplococcic
Biochemical:
-Alpha hemolytic
-No Lancefield grouping
-Capsular serotyping
-Quelling reaction
-Optochin sensitive
-Bile soluble (distinguish from viridians strep) |
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Term
| Haemophilus influenzae: Virulence Factors |
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Definition
Polysaccharide Capsule:
-Anti-phagocytic
-Antigenic variation
-Serotype B most virulent |
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Term
| Haemophilus influenzae: Etiology |
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Definition
Normal Flora: common in URT
-Both encapsulated and non-encapsulated (more common)
Transmission: person to person (droplet)
Common Age: 2-5 years old |
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Term
| Haemophilus influenzae: Pathogenesis |
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Definition
Pneumonia:
Encapsulated: similar to pneumococcal pneumonia
-Higher virulence/blood culture more likely (+) with Hib infection
-Less common as normal flora
Non-encapsulated: less virulent
-Predisposing factors include chronic bronchitis, emphysema, COPD
Acute Epiglottitis: also possible |
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Term
| Haemophilus influenzae: Clinical ID |
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Definition
Samples:
-Sputum
-Blood cultures (positive in 10-15% of patients; higher with Hib)
Shape: G(-) coccbacilli
Growth: fastidious (requires X and V) |
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Term
| Legionella pneumophilia: Virulence Factors |
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Definition
Existence inside amoeba:
-More resistant to disinfectants
-Can survive winter inside cyst of amoeba |
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Term
| Legionella pneumophilia: Etiology |
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Definition
Parasite of freshwater and soil protozoa: found in cooling towers, AC systems, plumbing, respiratory equipment etc.
Transmission: inhalation (no person-to-person spread)
Generally low virulence in humans: most people have Abs because of ubiquity |
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Term
| Legionella pneumophilia: Pathogenesis |
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Definition
Legionnaire’s Disease: severe pneumonia with high mortality rate
-2 to 10 day IP
Pontiac Fever: nonpneumonic febrile illness (mild flu-like symptoms); may be due to inhalation of dead or low virulence strains
-1 to 2 day IP
Disseminated Disease: rare
Disease Process:
-Tropism for lung alveoli and bronchioles
-Surface protein binds C3 to enhance its own phagocytosis (“coiling”); can also have bacteria-induced phagocytosis (no C3 bound)
-Intracellular parasite in monocytes and macrophages (multiplication normally inhibited in activated MØ)
Protein Expression in MØ:
-Prevent phagolysosome fusion
-Prevent acidification of endocytotic vesicle
-Induce accumulation of ribosomes and mitochondria around phagosome
-Facilitate iron scavenging from transferrin |
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Term
| Legionella pneumophilia: Clinical ID |
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Definition
Urine EIA test for soluble Ag
Does not Gram stain well:
-Silver stain (thin, pleiomorphic G(-) rod with filamentous forms)
Growth (slow): requires L-cysteine, amino acids, and ferric ions; also needs buffered medium (pH rest.)
Organism rarely found in sputum |
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Term
| Acinetobacter spp.: Virulence Factors |
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Definition
| Antibiotic Resistance: innately resistant to many classes of antibiotics |
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Term
| Acinetobacter spp.: Etiology |
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Definition
Environmental organism: lives in soil, water and on the skin of healthy people (esp. health care workers)
Frequent cause of nosocomial infections |
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Term
| Acinetobacter spp.: Pathogenesis |
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Definition
Pathogenesis (in immunocompromise):
-Pneumonia
-Serious blood or wound infections |
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Term
| Acinetobacter spp.: Clinical ID |
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Definition
| Shape: G(-) coccobacillus |
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Term
| Mycoplasma pneumoniae: Virulence Factors |
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Definition
Adhesin: binds sialic acid containing glycolipids or glycoprotens on bronchial epithelial cells
Hydrogen peroxide: damages tissue
Superoxide: damages tissue
AutoAb generation: may occur; reactive to lymphocytes, smooth muscle, brain and lung tissue |
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Term
| Mycoplasma pneumoniae: Etiology |
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Definition
Common in teenagers
Transmission: droplet spread (low ID) |
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Term
| Mycoplasma pneumoniae: Pathogenesis |
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Definition
Walking Pneumonia: less severe than other bacterial pneumonia
Disease Process:
-Colonization of bronchial epithelium interferes with ciliary action
-Inflammation and exudates contribute to pathogenesis
Secondary infection site: otitis media (non-purlent)
Sequelae: immunopathology results due to cross reactive Abs
-Hemolytic anemia
-Aseptic meningitis
-Pancreatitis |
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Term
| Mycoplasma pneumoniae: Clinical ID |
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Definition
No Cell Wall:
-No Gram stain
-No B-Lactam treatment
Bound by triple membrane containing sterols
No organism in sputum
Diagnosis:
-Circulating Ag
-Complement fixing Ag
(ELISA) |
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Term
| Chlamydia pneumoniae: Virulence Factors |
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Definition
Life Cycle:
-Elementary body (infectious stage)
-Reticulate body (metabolically active and replicates in the cell) |
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Term
| Chlamydia pneumoniae: Etiology |
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Definition
| Humans are only host: over ½ of adults are seropositive but reinfection can occur |
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Term
| Chlamydia pneumoniae: Pathogenesis |
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Definition
Pharyngitis
Bronchitis
Atypical/Walking Pneumonia: school aged children and young adults
Similar clinical picture to M.pneumoniae |
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Term
| Chlamydia pneumoniae: Clinical ID |
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Definition
Shape: G(-) outer membrane with no cell wall; coccobacillus
Glycogen (-) inclusions
Detection: immunofluorescence of outer membrane proteins or PCR |
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Term
| Staphylococcus aureus: Etiology |
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Definition
| Causes infection secondary to some other lung insult: for example, a viral infection |
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Term
| Staphylococcus aureus: Pathogenesis |
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Definition
Acute Pneumonia
Empyema: purulent infection of the pleural space (spread from infected lung)
Lung Abscess: complication of acute or chronic pneumonia |
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Term
| Staphylococcus aureus: Clinical ID |
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Definition
Samples:
-Sputum
-Lung abscess aspirate (may also use radiology to diagnose)
-Blood culture (if disseminated)
Shape: G(+) cocci in clusters
Biochemical:
-Catalase and coagulase (+)
Antibiotic susceptibilities required |
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Term
| Mycobacterium tuberculosis: Virulence Factors |
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Definition
Mycolic Acid (Cord Factor):
-Resistance to drying/disinfectants
-Promotes hypersensitivity granuloma
-Promotes inflamm. response/tissue damage
Lipoarabinomamman: cell wall glycolipid
-Suppresses T cell proliferation
-Prevents MØ activation
Sulfolipids: inhibit MØ phagosome-lysosome fusion
Catalase: degrades hydrogen peroxide
Ammonia Production: prevents acidification in phagolysosome |
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Term
| Mycobacterium tuberculosis: Etiology |
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Definition
Incidence highest amongst AIDS patients and immigrants
XDR TB: ~1% are extensively drug resistant
Transmission: aerosol inhalation |
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Term
| Mycobacterium tuberculosis: Pathogenesis |
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Definition
Primary Infection: Gohn complex formation (granuloma) and enlarged LNs
-unapparent most of the time
Progressive Primary TB: ~5% of primary infections; infection does not resolve and disseminates (bloodborne or miliary)
Reactivation TB: commonly reactivates at the apex of the lung (highest O2)
-Increased risk with age, alcoholism, diabetes or decrease immune function)
Disseminated TB: either due to progressive primary or reactivated
-Via lymph or erosion of necrotic tubercle in lung
-Infects liver, spleen, kidney, bone, or meninges |
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Term
| Mycobacterium tuberculosis: Clinical ID |
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Definition
Tuberculin Skin Test:
-Inject PPD (autolyzed bacteria, lipid, polysaccharides and NSs)
-Causes DTH reaction (local induration and erythema) if (+)
PPD+:
-Current infection (granuloman formation)
-Previous exposure (but not necessarily disease)
-BCG vaccine
PPD-:
-No exposure
-Prehypersensitivity stage (within 6 weeks of exposure)
-Loss of sensitivity (disappearance of Ag from primary complex)
-Anergy (immunocompromise)
Specimen Collection: sputum, biopsy or blood (if disseminated)
Staining: Acid Fast Stain
Growth: very slow; Lownstein Jensen or Middlebrook agar
Rapid ID:
-rRNA/DNA probes
-PCR to detect common insertion sequence |
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Term
| Pseudomonas aeruginosa: Virulence Factors |
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Definition
Adhesins:
-Protein pilus adhesin (bind asialoGM1)
-Non-pilus adhesin (binds mucus)
Alginate: polysaccharide capsule for biofilm formation; regulated in response to environmental signals
Elastase: protease that degrades lung elastin
Exotoxin A: ADP ribosylation EF2
Multiple Drug Resistance:
-Mutations leading to loss or porins
-Alteration of LPS |
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Term
| Pseudomonas aeruginosa: Etiology |
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Definition
CYSTIC FIBROSIS!
Nosocomial infections: water borne |
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Term
| Pseudomonas aeruginosa: Pathogenesis |
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Definition
Acute pneumonia
Empyema
Abscesses
Infections in CF:
-CF patients have defect in CFTR leading to decreased sialylation of surface glycolipid (asialoGM1)
-Alginate gel + excess mucus leads to barrier to phagocytosis AND antimicrobials
-Anti-pseudomonal Abs may be defective
-Lung tissue damage due to persistent colonization and elastase release
-Rarely spreads beyond lungs! |
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Term
| Pseudomonas aeruginosa: Clinical ID |
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Definition
Sample: sputum
Shape: G(-) rods
Biochemical: oxidase (+), aerobic |
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Term
| Aspergillus spp. (Fungus): Virulence Factors |
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Definition
No dimorphic growth phase
Infectious conidia: germinate to mold form
Hyphae: bind fibrinogen and complement components |
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Term
| Aspergillus spp. (Fungus): Etiology |
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Definition
Common environmental mold: emerging cause of nosocomial infections
Predisposing Factors
-Asthma
-Chronic bronchitis
-TB
-Immunosuppression
Transmission: inhalation of infectious conidia
Farmer’s Lung or Allergic Aspergillosis |
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Term
| Aspergillus spp. (Fungus): Pathogenesis |
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Definition
Conditions caused:
-Acute pneumonia
-Lung abscesses |
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Term
| Aspergillus spp. (Fungus): Clinical ID |
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Definition
Samples:
-Lung aspiration
-Bronchial lavage
-Biopsy
Structure:
-Septate hyphae with conidia
-Mold form grows rapidly, easily identified
Radiology: fungus ball in pulmonary cavity |
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Term
| Histoplama capsulatum (Fungus): Virulence Factors |
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Definition
Dimorphic growth phase:
-Mold in the environment (produces infectious conidia)
-Pathogenic yeast in tissue |
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Term
| Histoplama capsulatum (Fungus): Etiology |
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Definition
Environmental source: bird and bat droppings (Central and Southeastern US)
Transmission: inhalation of conidia (no person to person) |
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Term
| Histoplama capsulatum (Fungus): Pathogenesis |
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Definition
Exposure is common but disease is rare:
-Primary infection site is lungs
-Grows inside MØ and produces granuloma similar to TB (can disseminate to organs of reticuloendothelial system)
Normal Immune Response:
-T cell activation of MØ prevents intracellular growth
-Long-term immunity to re-infection |
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Term
| Histoplama capsulatum (Fungus): Clinical ID |
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Definition
Radiology: granuloma similar to TB
Sputum: NOT USEFUL
Blood or biopsy required
Growth (Slow): BAP or Sabouraud agar
Structure: dimorphic; mold forms tuberculate maccroconidia (finger like projects with spores)
Detection: widespread exposure and cross reactivity to other pathogens
-DTH skin reaction to mycelial Ag
-Complement fixing Ab test
-Immunodiffusion
-DNA probes |
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Term
| Blastomyces dermatitidis (Fungus): Virulence Factors |
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Definition
Dimorphic growth phase: similar to Histoplasma
Difference: yeast cells exist extracellularly, NOT in MØ |
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Term
| Blastomyces dermatitidis (Fungus): Etiology |
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Definition
Distribution: middle and SE US
Transmission: inhalation of conidia
More common in males |
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Term
| Blastomyces dermatitidis (Fungus): Pathogenesis |
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Definition
Chronic Pneumonia: PMN infiltration and granuloma formation (mimics pulmonary tumor or TB)
Dissemination possible:
-Chronic infection of skin and bone most common
-Possible even in subclinical infections
Immune Response:
-T cell mediated
-Cytokine-activated macrophages
-Large yeast cells can resist oxidative and non-oxidative killing mechanisms |
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Term
| Blastomyces dermatitidis (Fungus): Clinical ID |
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Definition
Large yeast cells with broad buds
Slow growth: ~4 weeks
Serodiagnosis: hard because of cross-reactivity with other fungi |
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Term
| Coccidiodes immitis (Fungus): Virulence Factors |
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Definition
Dimorphic Growth Phase:
-Mold (produces arthroconidia)
-Spherule (invasive tissue form that produces reproductive endospores) |
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Term
| Coccidiodes immitis (Fungus): Etiology |
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Definition
Valley Fever: common in SW US
Transmission: inhalation of arthroconidia |
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Term
| Coccidiodes immitis (Fungus): Pathogenesis |
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Definition
Usually mild disease: acute pulmonary infection with cough, chest pain and myalgia
Chronic Pneumonia: if decreased T cell response
-Dissemination possible (skin, bones, joints, meninges), although rare
Disease Process:
-Arthroconidia inhaled and are phagocytosed (PMNs, MØs)
-Spherule grows too large for phagocytosis and bursts, releasing endospores, which are endocytosed and prevent phagolysosome fusion (inflammatory rxn)
-Inflammation results in granuloma formation
Immune Response:
-Cell-mediated immunity to arthroconidia and endospores
-T cell anergy can result in chronic infection (due to heavy pathogen load after spherule burst) |
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Term
| Coccidiodes immitis (Fungus): Clinical ID |
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Definition
Detection of spherules in histological sections
Complement Fixing Ab titers predict outcome:
-Low: good CMI response
-High: disseminated and T cell anergy
Skin test of limited value: due to common exposure
Other ID Methods:
-Immunodiffusion
-DNA probe |
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Term
| Pneumocytsis carinii/jirovecii (Fungus): Virulence Factors |
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Definition
Protozoan: based on morphology and drug susceptibility
Fungus: based on rRNA and sequence homology with other fungi |
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Term
| Pneumocytsis carinii/jirovecii (Fungus): Etiology |
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Definition
Very common infection of generally low virulence: causes PCP in immunocompromise
-Premature infants
-Chemo patients
-Organ transplants patients
-AIDS (presenting manifestation)
-Use of corticosteroids
-Leukemia |
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Term
| Pneumocytsis carinii/jirovecii (Fungus): Pathogenesis |
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Definition
-Progressive diffuse pneumonia
-Other concurrent infections are common
-Alveoli filled with desquamated cells, organisms, monocytes and fluid (foamy appearance)
Symptoms: typical pneumonia signs absent
-Mild/low grade fever
-Non-productive cough
-Progressive dyspnea, cyanosis, hypoxia
-Death by asphyxiation |
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Term
| Pneumocytsis carinii/jirovecii (Fungus): Clinical ID |
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Definition
Sample: sputum (induced with hypertonic saline)
-Only useful in AIDs b/c of ↑ number of organisms
-Extracellular cysts and trophs
-Scattered cysts in contact with alveolar cells (characteristic of latent infection) |
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