Airborne Infections Flashcards
Human respiratory tract and its defence mechanisms
Physical defences:
- Filtration system: only small particles (<5um) will reach the alveoli
- mucociliary stream
- coughing
Alveolar macrophage
- primary defence of cells
- effector cells-phagocytic and microbicidal activities
- antigen presenting cells - induction of acquired T-cell responses
Alveolar inflammatory (innate) response
- influx of neutrophils (phagocytic and microbicidal) into the alveoli (diapedesis)
- in response to chemotactic factors such as complement to combat the infection
Adaptive response
- IgG and C - OPSONINS (promote phagocytosis)
- lymphois tissue providing T and B cells for the immune response
Humoral defences:
- IgA antibodies:
- predominant class in upper airways, more IgG in the lungs
- mainly dimer form, S-IgA, interacts with the mucin
- prevents attachment of microorganisms neutralisation of toxins
Other factors (of humoral defence)
- lung surfactant -may enhance bactericidal activity of macrophage and complement
- lysosyme - digests bacterial peptidoglycan
- Transferrin and lactoferrin - bind available iron
Diptheria
- once a major cause of death of children in UK in 1950’s
- controlled by vaccination
Corynebacterium diptheriae
- non-sporing, aerobic Gram +ve bacillus
- humans are only known reservoirs
- grows in the upper respiratory tract, usually throat, sometimes without harm to the host (carrier state)
- extracellular and does not invade the tissues
Pathogenesis of diptheria
-toxin-mediated disease
other factors: IgA protease - cleaves IgA
-Pili for mucosal colonisation
-consequence of inflammatory response- leathery pseudo-membrane of bacterial cells, dead inflammatory cells and fibrin
-cord factor (like M.tuberculosis) cell wall component, toxic for phagocytes
Diptheria Toxin
- tox gene is carried by lysogenic bacteriophage
- ADP ribosyltransferase for EF2 (elongation factor 2)
- -> involved in protein synthesis
- -> transfers ADP-ribose from NAD to EF2
- deaths in diptheria are due to a combination of partial suffocation & tissue-destroying effects of the toxin
Treatment (for diptheria)
- (horse) antitoxin - neutralises toxin
- Antibiotics - must be given early (penecillin, erythromycin)
Vaccine (for diptheria)
-triple vaccine DTaP
-formalin-treated diptheria toxin (toxoid) (D)
+ tetanus toxoid (T) and pertussis acellular vaccine (aP)
-vaccination does not prevent carriage and organism persists in community
Tuberculosis - a complex disease
1882 - Robert Koch identifies M.tuberculosis as causitive agent
-1 in 7 of all deaths in Europe due to TB
1993 - WHO declares that TB situation is a global emmergency
Mycobacterium tuberculosis
- slow growing, non sporing, gram +ve bacillus
- acquired by inhalation (tubercle bacilli survive for long periods in air/dust)
- from milk, bovine TB, before pasteurisation
Pathogenesis (M.tuberculosis)
- primarily a lung disease but may affect any organ including causing meningitis
- damage not due to toxin, but to host immune response trying to combat this persistant organism
Advanced TB
-lung tissue and lung function are permanently destroyed by these lesions
Antibiotics
-prolonged treatment (6-18 months) with combinations of isoniazid, rifampicin and other drugs
-emergence of resistant strains
MDR-TB (multi-drug resistant)
-resistant to at least isoniazid and rifampicin (two most powerful first-line drugs)
XDR-TB (extensively drug resistant)
-as above, + resistance to some second line drugs
Vaccine (TB)
- live attenuated vaccine BCG -Bacille Calmette-Guerin
- Isolated in 1904 as an attenuated mutant of M.bovis
vaccine efficacy ranges from 80%-0% due to
- vaccine batch variability
- human genetic factors
- pre-exposure to mycobacteria in environment
Resurgance of tuberculosis (since 1980’s) due to:
- neglect of healthcare programmes
- link to homelessness, drug-abuse
- rapid international travel
- link to AIDS (HIV destroys CD4 cells
Summary
Discussed pathogenesis and prevalence of two bacterial respiratory pathogens
– Corynebacterium diphtheriae – virulence largely mediated by one factor – toxin
– Mycobacterium tuberculosis – lifestyle more complex and difficult to control
– Highlighted the impact of both vaccination and antibiotic use on control
