Lecture 32 to 37 Respiratory system Flashcards
Single syndrome: multiple etiologies
Ex. Infectious pharyngitis
- Strep. pyogenes or unknown (most common)
- Rhinovirus, adenovirus, coronavirus, EBV
- HSV, HPIV, influenza virus Coxsackie virus, etc…
Defenses of respiratory system are often defeated by:
- smoking
- endotracheal intubation
- pollution
- suppression of cough reflex
- predisposing infection
- disruption of homeostasis: age, malnutrition, immunosuppression, etc…
Interplay bw a professional and secondary pathogen
Ex. flu & pneumococcal pneumonia
Suggested underlying mechanisms
- changes to RT
- epithelial damage
- airway function altered
- up-regulation and expsoure of receptors
- alteration of innate immune response
- not limited to flu virus; observed w multiple respiratory viruses with the top ones are:
- Strep. pneumoniae
- Staph. aureus
- Hemophilus influenza
Microflora (URT)
- corynebacterium
- enterobacteriaceae
- Staph
- Strep
Haemophilus
- Moraxella
- Mycoplasma
Tranmission & acquisition
Exogenous:
- inhalation of infectious droplets:
- small droples
- dried respiratory droplet nuclei w mucin
- self-inoculation of eyes, etc..
virus persistence on dry inanimate surfaces
Survival times
- adenovirus: 7 d to 3 mo
- rhinovirus: 2 h to 7 d
- coronavirus: 3 h; significant w regard to fomite-mediated transmission & survival in dropletss
- RSV: up to 6 h
Endogenous infections
- Endogenous infectons usually due to microflora
- situations that can predispose to RT infection
- nl flora move to unusual location, Ex. smoker, , COPD, CF, asthma, chronic bronchitis, age
- preceding infection causing damage -> secondary infection
- aspiration of URT flora, Ex. Enterobacteriaceae into lungs -> aspiration pneumonia
Some pathogens require specialised growth media that is not standard
- Bordetella pertusis: Bordet-Gengou
- C. diphtheriae: Tinsdale agar
- (slide 23 for rest)
6 major families of Viral agents of RT infections
- adenoviruses
- rhinoviruses
- coronaviruses
- HPIV
- RSV
- influenza viruses
- Emerging: non-polio picornaviruses
Some respiratory viruses do NOT exert their main pathology in respiratory tract
major examples
- measles: both rubella & rubeola
- VZV aka HSV-3
- smallpox
- coxsackie virus
- Norwalk virus
Taxonomy of respiratory infections
URT
- sinusitis
- rhinitis
- otolaryngitis
- laryngitis
- pharyngitis
LRT
- bronchitis
- bronchiolitis
- pneumonia: community-acquired (acute, subacute, & chronic) and nosocomial (acute)
Viruses directly involved in RTI
- Rhinoviruses: (+) RNA, type of Picorna virus
- Adenoviruses: linear ds DNA
- Influenza virus: segmented RNA
- RSV: (-) RNA
- Corona virus: (+)
- HPIV: (-) RNA
Infectious rhinitis: microbial causes
Viral agents
- rhinovirus
- adenovirus
- coronavirus
- Non-polio picorna virus Ex. EV-D 68
Bacterial agents: no significant bacteria
Rhinoviruses
- Sx: common cold, fever is rare in adults
- virus family: Picornaviridiae
- Medically signifiicant: Enteroviruses, polioviruses
- Icosahedral, non-enveloped
- Pathogenesis:
- Attachment to ICAM-1 cell receptor via surface clef/canyon
- viral replication & cell to cell spead
- cell damange, cilia immoblised, viral shedding
- Antigenic drift leading to 115 serotypes
- Epi: all ages, young children more severe, humans sole reservoir
- Transmisson: direct contact, respiratory droplets, survival time 2h to 7 d
- Rx: Diversionary care to treat common cold
Adenoviruses
- Sx: pharyngitis, conjunctivitis
- Family: adenoviridae
- Genus: Mastadenovirus
- Replication: Class 1 (nucleus)
- Etiopath: interference w host immune response
- E1A*: hijacks cell
- activates viral gene transcription
- binds cell growth suppressor: p105Rb promotes transformation
- deregulates cell growth
- inhibits activation of interferon response elements
- E1B: binds p53 & promotes transformation & blocks apoptosis
- E3: prevents TNF-alpha inflammation
- fibre protein: enables attachment to host cell receptor
- receptor varies w viral serotype
- Serotypes 2 & 5= Coxsackie Adenovirus Receptor (CAR)
- cell surface glycoprotein belings to IgG superfamily
- Penton base has toxic activity
- inhibition of cell mRNA synthesis
- cell rounding
- tissue damage
- E1A*: hijacks cell
- Epi: widespread, most infections occur in children
- can be associated w ocular, respiratory, or GI systems
- outcomes of adenoviral infection
- Lytic: ex. mucoepithelial cells
- Latent: ex. adenoid cells
- Transmission: swimming pools, aerosols, direct contact, fomites, fingers
- 7 d to 3 mo survival time
Coronaviruses
- Sx: common cold, SARS
- Family: Coronaviridiae
- HCoV-229E, HCoV-OC43, SARS-CoV, MERS-CoV, etc…
- enveloped, helical nucleocapsid, characteristic fringe=surface/”spike” glycoproteins
- Genetic material: ss (+) linear RNA
- class IVb replication
- Coronavirus S protein: “spike” protein
- Peplomers: 20 nm projecting surface proteins, define tissue tropism, attach to proteins or carbs, site of main antigenic epitopes: neutralising Ab
- Etiopath: specifics unclear
- replication optimal @ 33-34C
- occurs in ciliated nasal epithelium
- no good animal model for major CoV types; difficult to isolate & grow
- Epi: isolated from humans and animals (no cross-infect)
- total # serotypes undetermined
- re-infection by same serotype possible
- Transmission: mostly via droplet; fecal-oral route also possible
- surival time: 3 h

Infectious pharyngitis: microbial causes
Viral agents
- rhinovirus
- adenovirus
- coronavirus
Bacterial agents
- Strep. pyogenes Group A
- Strep pneumoniae
- Corynebacterium diphtheriae
Sx: strep. throat sx, fever, swelling and narrowing, etc…
Strep. pyogenes
- Sx: pharyngitis, strep. throat
- Group A strep.
- Pus formation due to leukocidin production
Virulence factors
- lack catalase (facultative anaerobes)
- Growth enhanced by CO2
- nutritionally fastidious
- nl culture medium=blood agar (BA)
- yeast extract + peptone +5% blood
- Beta -> hemolysin enzyme from bacteria to lyse cell membrane so true hemolysis
- (Alpha-> reduced (not true hemolysis) so green; A disk: Bacitracin inhibits growth of Group A)
- P disk: inhibits pneumococcus
- nl culture medium=blood agar (BA)
Corynbacterium diphtheriae
- Sx: severe pharyngitis (diphtheria)
- 4 biotypes: gravis, mitis, belfanti, and Gram +ve intermedium
- other non-pathogenic Corynebacteria spp. are members of nl flora in pharynx, nasopharynx, and on skin.
- other medically-important species:
- C. jeikeium: associated w bacteraemia, IV cath colonisation
- C. minutissimum: RTI, wound infections
- Etiopath:
- organism is non-invasive and does not enter into blood
- pharyngitis can be severe enough to block airway -> suffocation
- main virulence factor= diph. exotoxin
- genes for toxin acquired via lysogenic conversion.
- toxin is responsible for local and systemic sx
- inflammation & formation of pseudomembrane
- damage to organs
- Sample & Dx: throat/nasopharyngeal samples
- screen: CYS Tellurite plate
- Dx: CYS Tellurite plate + BA (CTBA) -> Tellurite inhibits the growth of most URT bacteria.
- Immunodiffusion asasy (Elek test): Gold
- growth = diagonal bands of precipitin = +ve test
- PCR for tox gene although non-toxigenic strains produce a repressor for gene -> risk of fp
- methylene blue (very non-specific)

Infectious sinusitis & otitis media: microbial causes
Viral agents: same as infectious rhinitis
- rhinovirus
- adenovirus
- coronavirus
Bacterial agents
- Strep. pneumoniae
- H. influenza
Hemophilus influenza
- sx: otitis media, pneumonia, epiglottitis
- H. influenzae, Gram -ve; pleomorphic, facultative anaerobe
- nl component of URT flora
- serotyped according to capsule (a -> f) or described as non-typeable
- Type b = particularly associated w invasive disease
- non-typeable strain carried by: 50-80% of people
- Etiopath:
- pili
- non-pilus adhesins Ex. P-2 outer membrane protein; attaches to sialic acid-containing mucin oligosaccharides
- LPS: impairs ciliary function
- antiphagocytic capsule composed of polyribose ribitol phosphate (PRP)
- IgA proteases: > 30 different proteases id
- Culture & Dx
- Caogulase: -ve
- Catalase: +ve
- Culture: requires chocolate agar w hemin & NAD
- will not grow on blood agar bc it cannot lyse the RBC to obtain hemin and NAD.
- is the only haemophilus species that requires both.
Infectious bronchitis & bronchiolitis: microbial causes
Viral agents
- influenza virus
- adenovirus
- RSV
Bacterial agents
- Bordetella pertusis
- Mycoplasma pneumonia
- Chlamydophilia pneumonia
Bordetella pertussis
- Sx: whooping cough (chronic bronchitis)
- B. pertussis: small, Gram -ve coccobacillus
- some Bordetella toxins
- TCT=tracheal cytotoxin
- PT=Pertussis toxin
- ACT=adenylate cyclase toxin
- DNT=demonecrotic toxin
- LOS
- Filamentous haemagglutinin (FhA)
- Etiopath: associated w virulence factors
- Adhesion: FHA, PT, fimbriae
- Growth & toxin release: PT, ACT, TCT
- Local & systemic pathology: TCT, PT, DNT, LOS
- Whooping cough: stages
- Incubation: 1 wk
- Catarrhal sx: common-cold (transient) leading to more serious sx
- Paroxysmal: inspiratory whoop so severe that the children will vomit
- Convalescence
- Culture & ID: nasopharyngeal swab or secretions
- flexible wire inserted into nasal passage; do not use cotton containing fats which is toxic to Bordetella
- organism is very susceptible to drying
- B. pertussis is nutritionally fastidious -> require charcoal blood agar + cephalosporin (Ex. Bordet-Gengou)
- PCR
- Prevention: part of DaPT vaccine (aP)
- Types of vaccines:
- whole cell (formalin-inactivated)
- Acellular components, ex. Fha, PT
- aP= acellular Pertussis
- lower rate of side effects
- Types of vaccines:
Human parainfluenza viruses (HPIV)
- Sx: croup; bronchitis
- Virus family: paramyxoviridae (-ve) ss RNA
- Subfamily: paramyxovirniae & pneumoviriniae
- Genera: HPIV 1 &3 (respirovirus), HPIV-2, HPIV-4 (Mumps), morbillivirus (measles), megamyxovirus, Hendra virus, Nipah virus
- Genus: RSV, mPV
- Enveloped, linear ss (-) sense RNA virus
- Glycoprotein with Hemagglutinin-Neuraminidase (HN)
- Fusion factor (F)
- Etiopath:
- Transmission: inhalation of large-droplet aerosols
- Fusion factor (F) involved in viral entry
- Release of nucleocapsid into cytoplasm occurs following fusion of viral and host cell envelope.
- Virulence factors (below) inhibit IFN-alpha & beta production and signaling pathways.
- Inflammation and mucosal edema can lead to narrowing of airway and stridor.
- Virulence factors
- P/F proteins: immune evasion
- F proteins (fusion proteins): role in syncytium formation
- HN protein: structural Hemagglutinin & Neuraminidase
- L protein: multifunction polymerase
- M protein: matrix structural protein
- P/F protein (non-structural protein): role in evasion of immune response by blocking IFN expression & signalling






