7.5 Flashcards
Streptococcus pneumoniae
Gram posi5ve cocci – Diplococci
– Aerotolerant anaerobe – Non-‐spore forming
– Encapsulated
• Main cause of community-‐ acquired pneumonia worldwide
– >1,000,000 deaths annually
– >1.6 M new U.S. cases annually
Entry S. pneumoniae
Access to lower airway
– Usually cleared by barrier/innate immunity
• Risk factors for establishment of infec5on – Viral infec5on (esp. influenza)
– Smoking
– Loss of consciousness (aspira5on)
– Edema (fluid) in lungs for any reason
– High risk comorbidi5es, age, and demographics
• (e.g. elderly, HIV, alcoholism, african-‐american, certain
cancers)
– Seasonality (Winter/spring)
Mul5plica5on/Spread: Pathogenesis in 4 stages
I. Alveoli fill with fluid
II. Early consolida5on phase
– Suppura5ve (neutrophils) inflamma5on
III. Late consolida5on phase
– Alveoli and airways are packed with neutrophils
– Affected 5ssue is solid instead of spongy
IV. Recovery phase
– Macrophages phagocytose debris
– Normal architecture is re-‐established
hKp://www.meddean.luc.edu/lumen/MEdEd/ Radio/curriculum/Medicine/pneumonia1.htm
Other disease manifesta5ons
O55s media in children
• Poten5al sequelae to pneumonia in adults
– Pleural effusion = fluid in the chest outside lungs – Bacteremia à Meningi5s
Pneumococcus -‐ Therapy
Penicillins and other β-lactams
– Resistance is a concern unlike group A Strep. • Macrolides
– Erythromycin, Azithromycin
• Fluoroquinolones – Levofloxacin
Vaccine
Vaccine products are comprised of polysaccharide an5gens (capsular) from mul5ple strains of S. pneumoniae
• Children
– Rou5ne 4 doses 2-‐15mo
– Addi5onal protocols for older children with addi5onal risk factors
• Adults
– All >65 years old
– <65 years old with addi5onal risk factors
Legionella pneumophila
Gram nega5ve pleomorphic rod
• Obligate aerobe
• Fas5dious = special condi5ons for cul5va5on in lab
• Cysteine requirement is iden5fying characteris5c
Encounter L. pneumophila
Contaminated water
– L. pneumophila is a parasite of protozoa. – Biofilms with protozoa and other bacteria – Thermotolerant withstands 46∘ C – Environmental aerosols (Not spread by cough)
Mul5plica5on/Spread L. pneumophila
Bacteria in alveoli phagocytosed by alveolar macrophages
• Virulent strains mul5ply within autophagosomes (double membrane of rough endoplasmic re5culum)
• Inflamma5on -‐> Acute bronchopneumonia – Suppura5ve (neutrophils)
– Recruitment of more macrophages
– Abscess forma5on
Damage/Immune response L. pneumophila
Cell-mediated immune response
– Includes secretion of IFN-γ
– Causes iron sequestrationà decreases replication of bacteria
• Virulence/Proinflammatory mechanisms
– Survival in macrophages – LPS, Flagellin
• LPS has some cytotoxic effects
• FlagellinàEnhances inflammation via innate immune system (TLR-5)
(Toll-like Receptor 5)
Therapy L. pneumophila
An5microbial drugs with good intracellular penetra5on
– Macrolides
– Fluoroquinolones – Tetracyclines
• Penicillins are not effec5ve because they do not achieve therapeu5c concentra5ons in the macrophages.
Bordetella pertussis and parapertussis
Gram nega5ve rod • Obligate aerobe • Cause of whooping cough – Poten5ally fatal in infants – Morbidity in kids and adults • VERY CONTAGIOUS – AKack rate ~90% – 1 person can infect 12-‐15 others
Pertussis Encounter, Entry, Spread
Infected people
– Adults are believed to be reservoir
• Nasopharynx colonized • Organism accesses
trachea/bronchi
– Ciliary Adherence via
• Filamentous hemagglu5nin (Fha)
• Pili (a.k.a. Fimbriae) • Pertac5n (a protein)
Damage -‐ Toxin produc5on
B. pertussis P. parapertussis • NO PERTUSSIS TOXIN Damage -‐ Toxin produc5on • Pertussis toxin • Adenylate cyclase/ hemolysin à Both upregulate host cAMP à Decreased neutrophil func5on à Inc. capillary permeability à (results in edema) • Endotoxin (as with other G-‐ bacteria)
Clinical course: catarrhal stage
First stage = catarrhal stage
– Catarrhal means really really bad runny nose
• Looks like a bad cold at this point
• Organisms are spreading down the respiratory tract
• EXTREMELY CONTAGIOUS
Vaccines have
acellular Pertussis
– DTaP (Diphtheria, Tetanus, acellular Pertussis) – Rou5ne 5 doses (2, 4, 6 months, 15mo, 5 y)
– Tdap (Tetanus, Diphtheria acellular Pertussis) – 11-‐64 years old
– Pregnancy (3rd trimester)
– Lower doses of Diptheria and Pertussis components
Laboratory diagnosis is tricky
• Fewer organisms shed in paroxysmal phase
• (Clinical suspicion is lower in the catarrhal phase)
• Deep nasal swab – Bacterial culture
• Nasal flush – PCR
• Diagnosable <3 wks of cough onset
Bordatella bronchisep
• Canine infec5ous tracheobronch55s • Part of “kennel cough complex” • Very rarely affects human beings – HIV+ – Chemotherapy pa5ents
Mycobacterium spp.
Tuberculosis
– M. tuberculosis – Highly Contagious – M. bovis
– M. avium-‐intracellulare
• Leprosy
– M. leprae – Contagious
• Opportunis5c Disease caused by rapidly growing mycobacteria (RGM)
– M. smegma
Mycobacterium spp. are acid fast bacteria
Obligate aerobes • Non-‐spore formers • Thick, waxy cell wall • Mycolic acid binds carbol fuscin dye
Immunology of granuloma forma5on
Mul5plica5on in MΦs
• Ac5va5on of CD4+ (TH1) – Clonal TH1 expansion
• Cytokine profile of – IFNγ, IL-‐12, IL2
• Recruitment of more MΦs
Diagnosis Mycobacterium
Intradermal skin test – Use of killed an5gen “tuberculin” “PPD” – Relies on Delayed Type Hypersensi5vity • Ac5va5on of specific CD4+ • Local inflamma5on at injec5on site • False +s, False –s possible • Acid-‐fast sputum exam • Culture – Very slow growing PCR
M. Leprae
Granulomatous disease – Similarimmunology toTB
• Organism prefers lower temperature (skin)
• Spread via respiratory route
• Two forms of disease: – Tuberculoid Leprosy – Lepromatous Leprosy
Tuberculoid Leprosy
Milder form of disease
• May be self limi5ng
• Very few bacteria present in lesions
