Pathogens 2 - Enteric infections Flashcards
What are Enterobacterales?
-Enteric Gram-negative bacilli >INTESTINAL PROBLEMS
-Escherichia Coli
-Klebsiella pneumoniae
-Proteus mirabilis
How is water absorbed?
Regulation of fluid uptake depends on three things:
1. The ability of enterocytes to break disaccharides down into monosaccharides
2. The availability of sodium to facilitate uptake of the monosaccharides into the enterocytes
3. The ability of negatively charged ions and water to follow these into the enterocyte
What are our primary defensive cells?
Which cells act as surveillance cameras, waiting and reporting on activity, ready to call for reinforcements if needed?
-Paneth, mast and goblet cells
-Dendritic and M-cells
How are microorganisms pushed along the lumen?
What happens when microorganisms get pushed against the enterocyte layer?
What can grab microorganisms that get too close to the enterocytes?
-By the flow of material
-Mucus from goblet cells trap them, and allow them to be pulled away before they can bind
-Dendritic and M-cells which then pass information through to B-cells and TH0 cells in the Peyer’s patches and other lymphoid tissue
What do B-cells do without TH cell support?
-B-cells recognise PAMPS and produce T-independent IgA, to agglutinate the bacteria and stop them adhering
What do dendritic cells do? How is there role impacted because there is no inflammation ?
-Present dietary and non-inflammatory debris to TH0 cells
-Dendritic cells cannot produce co-stimulatory molecules, so the TH0 cells that recognise the antigen do not get co-stimulation and will die
What happens if a microorganism stays for too long?(Paneth cells)
-Paneth cells will phagocytose the bacteria that adhere to them, recognise their peptidoglycan with NOD-like receptors and produce alpha defensins, chop up bacteria.
What if a microorganism is really persistent and its virulence factors allow it to survive and even invade the lamina propria?
- LP Enterocytes +macrophages express TLR on the side of lamina propria > Bacteria encountering the apical side of them will NOT cause inflammation, but those encountering the basolateral side WILL.
>ROBUST INFLAMMATORY RESPONSE
The organism may have virulence factors that also let it survive innate immunity! What is the result of this?
- Pathogens release toxins that alter enterocyte function
- Pathogens release toxins that kill epithelial cells
What could be the cause of autoimmune diseases? Link to the idea that virulence factors have been able to survive innate immunity.
-Inflammation equips the dendritic cells with co-stimulatory molecules. They may accidentally activate the “wrong” T-helper cell and result in an immune response against dietary or commensal bacteria that you didn’t want.
What is the difference between food poisoning, gastroenteritis, dysentry?
–Just to add about dysentry: burrows into the lamina propria > Key symptom of dysentery is the presence of blood in the stools, due to damage to the capillaries during invasion
Enterotoxigenic vs Enterohemorrhagic Escherichia Coli?
-INTESTINAL PROBLEMS
- Enterotoxigenic Escherichia Coli : Severe gastroenteritis
-Enterohemorrhagic Escherichia Coli : Dysentery
How do ETEC and EHEC colonise GI?
Why does Uropathogenic E.Coli not colonise?
- Exposure…..
-Adhere to enterocytes via Type 1 Pilli = midgut colonised = toxigenesis or invasion or both
-K-antigens in their capsule that help resist stomach acids
-No adhesins that will recognise enterocyte surface molecules and, cannot bind for long enough to get into position to cause infections
Pathogenic E. coli have lots of
- Virulence factors : What are these?
-Ways to escape immunity
What makes adhesion more likely?
EHEC and ETEC both follow the same process to a point (adhesion) > diverge > they both produce a different toxin. What does this result in?
- Gastroenteritis vs dysentery
How does the Heat-labile toxin released by ETEC caused epithelial damage?
-plasmid-encoded exotoxins -A5B exotoxin
- B subunit binds to enterocyte, encourage to take up A subunit > processed and released into cytoplasm
- Active A subunit phosphorylates Gs > AC > cAMP > PKA (signalling cannot be halted) > drives ATP mediated pumping of Cl- into gut lumen
- Cl- pump remains working even in high concentrations as signalling is on full blast
- Forces K+ and Na+ back out into lumen brining in water with them.
How does Shiga-like toxin and Verocytotoxin released by EHEC kill epithelial cells directly?
-A5B exotoxin
- Attachment of EHEC to enterocytes causes them to “shuffle out” their microvilli from the top of the cell + loose them> attachment of the bacterium and release of the toxin directly to the surface of the cell.
- B-subunit binds to G3b on cell surface > taken up by endocytosis
- A-subunit is liberated into cytoplasm and chops up 28s subunit of large (60s) ribosomal unit > inhibits protein synthesis and causes cell death
- Punches holes in the GI epithelium and allows the bacteria access to the lamina propria.
How do we enable recovery from EHCT AND ETEC?
-Providing adequate fluid support to allow the immune system time to make antibodies against the toxins
>clean water, glucose, sodium, potassium and chloride to replace what is lost and to force the SGLT-1 transporters into action.
If you have a healthy gut microbiome then you are not going to have C. difficile growing in your gut. What causes infection then?
-Broad-spectrum antibiotics kill many of the “resident” bacteria in the gut > provides correct environment for C. difficile to germinate and release toxins
