Final - Lecture 19 Flashcards
What bacteria causes anthrax?
Bacillus anthracis
Who does anthrax affect?
- Warm blooded animals (livestock, humans)
- Herbivores: susceptible to acute form
- Carnivores and reptiles: relatively resistant, affected by less acute form
Bacillus anthracis
- Gram +ve, non-motile spore forming
- grows well on common median (blood culture)
- vegetative form: multiplies and kills host
- Spore form: survives environment
What is the predominate form of Bacillus anthracis in the environment?
- spores; nutrient poor enviro and presence of O2 to sporulate
Where do spores germinate?
enviro rich in amino acids, nucleosides, glucose aka blood or tissue
Are spores resistant?
- very resistant: temp extremes, pH, desiccation and chemicals, UV light
How long can Bacillus anthracis survive in a spore form?
50-250yrs
What are the three main forms of anthrax in humans?
- cutaneous
- gastrointestinal
- inhalational
Cutaneous Anthrax
- 95% of cases; enters through cuts or abrasions
- 1-12 day incubation
- infection begins as: small papule to vesicle to eschar and sometimes secondary vesicle
What is the fatality rate of cutaneous anthrax?
-5-20% without antibiotics
-<1% with antibiotic treatment
Gastrointestinal Anthrax
- appears in livestock ingesting spores; appears in ppl consuming contaminated meat or drink
- 1-7 day incubation
- oropharynx: sore throat, dysphagia, fever regional lymphadenopathy
- Lower GIT: acute necrosis and inflammation, nausea, vomiting, dysentery, fever
Fatality rate of Gastrointestinal Anthrax?
25-65% without treatment
Inhalational Anthrax
- ‘Woolsorter’s disease’
- incubation 1-43 days
- symptoms: cough, fatigue, fever
Fatality of inhalation anthrax
- 85-97% without antibiotics
- 75% with antibiotics
- 45% with intensive therapy
Pathogenesis of anthrax
- lung
- macrophage engulphs spore
- spore germinate in macrophage in lymph nodes and release from dead macrophage
- vegetative bacteria divides extracellularly and releases toxins
- mild illness to fulminating disease and raid death
What two plasmids do important anthrax toxins promote disease on?
- pOX1: encodes for protective antigen, lethal factor and edema factor
- pOX2: encoded for proteins that synthesize polyglutamic acid capsule: helps protect dividing bacteria to evade engulfment and phagocytosis
What are the 3 actions btw anthrax toxins and plasmids?
- Protective antigen combines with lethal factor to form lethal toxin
- Protective antigen combines with edema factor to form edema toxin
- 7x PA form heptamer: pore in cell membrane and allows lethal and edema toxin inside the cell
What is the common affect of lethal toxin?
Impairment of host defense and immunity
- virtually all cells involved in immune fxns require MAPK pathways for proper fxn
- alters innate immunity and adaptive immunity
How does lethal toxin affect neutrophils?
- inhibition of chemotaxis
- decrease production of superoxide anions
- cripples innate immunity
How does lethal toxin affect macrophages?
reduce chemotaxis and phagocytosis
What are the stages of lethal toxin?
- macrophage death (toxin induces selling and lysis of macrophages)
- initially univalent cation permeability followed by ATP depletion
- loss of mitochondrial fxn
- shutdown of protein synthesis and eventual loss of membrane integrity
- activation of macrophage with agonists of toll-like receptors makes macrophages more susceptible to lethal toxin
What are the cell mechanisms for macrophage death induced by lethal toxin?
- Nalp1B gene
- Modulation of Wnt target genes
- LRP6 and co-receptor Wnt target genes
- Lethal Toxin blocks survival pathways of activated macrophages
How does lethal toxin affect adaptive immunity?
- impairment of cognitive interactions btw dendritic cells and T lymphocytes- priming lymphocytes
- decrease in up-regulation of co-stimulatory molecules
What are the 2 microenvironments?
- low-lying depressions with standing water and devitalized plant material
- rock lands with dry courses of water
