Mycobacteria Flashcards
Mycobacteria description
Aerobic
Rod shaped
Non spore forming
Charact by large amounts of CW lipid incl mycolic acids
Acid fast bact
Sometimes form easily broken filaments showing similarity to actinomycetes
Virulent strains generally take longer to culture
Can be opportunist or obligate pathogens and some can only be grown in assoc with host cells
All thought to derive from single ancestor due to genetic similarities
Mycobact bovis
Cause bovine TB and TB in pigs rarely in sheep dogs and horses
Mycobact paratuberculosis
Cause Johnes dis in cattle sheep deer and goats
Mycobact avium
TB in birds
Poultry v susceptible
Pigs suscept but no cattle
Sporadic horse dog and cat cases
Mycobact leprae, lepraemurium, ulcerans, kansasii, fortuitum and chelonae
Cause leprosy and ulcerative lymphangitis in many species
Mycobact tuberculosis
Cause human TB
Human TB and human co evolution
One of top 3 mortality worldwide dis
Evidence back to ape like ancestors
Bovine form first recorded with cattle domestication
Highly prevalent in third world assoc with poverty and high HIV incidence
Multi drug res strains are starting to emerge and some completely drug res strains
Human TB control
Major goal
BCC bacc not effective enough to eradicate
Why are human and bovine TB similar
Mtb and Mb are 99% similar on a genetic level
Mb human importance
Zoonotic can cause human TB
Pre milk pasteurisation many human TB cases caused by Mb
Bovine TB conseq
Major economic loss
80-100 mill per yr (UK gov cost)
Issue with bovine TB control
Incidence rising despite control measures though still geographically isolated in UK but endemic areas incr in size and now being found in previously TB free areas
Attempt to control bovine TB
5 pt plan Improve detection and diagnosis Incr research Asses wildlife reservoir in badgers and how it affected dis spread Dev vaccines
Control methods
TB skin test and slaughter policy
Other methods may be used as confirmatory test
TB test used for
Detection of current or previous TB infection
Confirmatory tests
Blood based detection
Culture and stain in lab
TB test process
1.2.3.4 yr interval dep on freq of TB in area. Intradermally inject purified pro derivatives amd test for delayed type hypersensitivity after 72hr
comparative test with avium done as exposure to avium could hive false +ve to bovis
Animal ID, clip side of neck 2cm radius in 2 spots 13cm apart skin fold taken PPD inject usually avium in upper
Remeasure 72hr later
TB test results
If bovis reaction is 4mm greater than avium it is a reactor
If 1-4mm then retest in 40-60d and rest of herd analysed using severe interp - 1mm
What method being used to improve TB detection in low incidence areas ti maintain TB free status
Blood based detection method (cheaper and quicker) where spec IFN gamma resp to bovine PPD measured along with skin test. More animals test +ve so more culled. Tests a diff part of imm resp and can detect earlier after infection
Factors affecting TB spread
High animal stocking densities
Immunosuppression
Cattle to cattle spread can occur
Role of wildlife reservoirs - controversial esp badger
Countries without wildlife TB reservoirs
Australia, vigorous skin test and slaughter eradicated the dis
Uk TB wildlife reservoir and methods to control
Badgers, evidence linking to bovine TB is compelling.
Can be Heavily infected with Mb and excrete large bacillus quantities that can survive on pasture for a long time
Cattle and badgers from similar location often infected with similar Mb substrain
But randomised badger culls have not decr TB incidence, it has cont to incr mabe due to disruption of badger grps that moved outside their normal area due to a key member of the grp being culled
Now trying BCG vacc of badgers at single site and monitoring neighbouring herds
Other wildlife reservoirs and their locations
Possums NZ
White tailed deer USA
Wild boar Spain
BCG vacc
Live Attenuated Mb derived from continual growtb on slices of potato over many yrs so caused a loss in many Mb genome regions
Administer subcut
Not always effective but unsure why
Has been trialled in cattle cam be used alone or in prime boost strategy (given 1st with boost of DNA or pro later) but these animals react +ve to skin test and gamma test so need DIVA test
Conseq of being IC bact to imm resp
Cell med imm key to control esp macro act via IFN gamma released by stim T cells
Humoral imm and Ab secr not commonly seen in TB but can be observed in late stages and correlate with disease progression
Imm resp to mycobact
Initiated via uptake macro or DC lining resp tractor in lungs induce cascade leading to granuloma form within tissues (lungs and lymph nodes)
Success assoc with cell med imm and secr of IFN gamma
Granuloma
Aggregate of epitheloid hustiocytes
The cells have large vesicular nuclei, plentiful eosinophilic cytoplasm and are often elongated
Cell types in granulomas
Macro (sometimes fuse to form giant cells)
Langhan’s giant cells are charct of TB with a horse shoe nulcei arrangement at one pole
B and T cells
Necrosis of TB granuloma
Caseous necrosis
Gen large amount of released cellular matter
Fibrin wall around granuloma formation
CD4+ T cells release TNF alpah and LT alpha 3 req for fibrin wall depositiony
Virulence factors of mycobact
Protective glycolipid cont CW making bact hydrophobic resistant to lysis and helps resist O and N radicals
Also prod enz eg superoxide dismutase to res intermediates
CW and CM structure
CW has a plasma mem cont pro, lipoarabinomannan, phosphatidylinositol
Peptidoglyc layer has 10% N glycolymuramic acid residue cov nattached to arabinogalactan with phophodiester bonds penultimate and final arabglyc are attached to mycolic acids of high molecular weight
CW comp and fx
Mycolic acid- resist phago digest
Sulfatides- prev phagoso-lysoso fusion and phagocyte action
Cord factor- inhib phagocyte chemotax, activation and phag-lys fusion and digestion
LAM- prev phagocyt act and digestion within phag
Mycosides- prev IC killing and digestion
