What does the mucus blanket do in the intestines?
What produces them?
What do they contain?
Forms a selective barrier
mucins, ions, antibodies, antimicrobial peptides, and bacteria
How do commensal organisms co-exist with the mucus blanket?
- specific binding via adhesins
- grazing on sugars from mucus oligosaccharides
- grazing on mucins
How does bacterial infection change expression of the mucus blanket?
LPS and bacteria cause upregulation of the MUC gene, increasing mucin expression
What are some defenses pathogens have developed to circumvent mucus?
- Flagella/motility proteins
- Secretion of mucus-digesting enzymes
- Disturbance of tight junctions
- Toxins that reduce mucus production
Other than a physical barrier, how does mucus protect against bacteria?
- Secretion of IgA
- Acidification of the Environment
- Oxygen Radical Production
- Lysozymes/Acid hydrolases (digest bacteria)
- Lactoferrin (competes for nutrients)
What are five anti-microbial proteins produced by the Paneth cells?
What do they do?
- a-defensins: form pores in cell membranes to disrupt their integrity
- Lysozyme C: hydrolyzes bacteria cell walls
- Phospholipase A2: hydrolyzes bacterial cell membranes
- RegIIIy- Binds to pepetidoglycan of Gram + (induced by TLR activation)
- Cryptdin related sequence: anti-microbial
How do pathogens evade anti-microbial peptides?
- Capsule formation
- Surface charge modification
- Protease secretion
- Efflux pumps
- Modultate AMP expression
Which antibodies are secreted?
How is mucosal IgA different from serum IgA?
IgA, IgM, IgG, IgE, and IgD
Serum IgA is mostly monomeric, while mucosal IgA is mostly polymeric
By what mechanisms does IgA work against pathogens?
How have pathogens evolved against IgA?
- Inhibit adherence to mucosa
- Trap within mucins
- Neutralize viruses
- Neutralize enzymes/toxins
- IgA proteases
- IgA binding proteins
How are bacteria in the gut classified?
How does microbial composition of the microbiome affect disease states?
Symbionts, commensals, and pathobionts
Many inflammatory disease states are associated with overgrowth of pathobionts or undergrowth of symbionts/commensals. (ASSOCIATED, not necessarily caused by)
How does the microbiota change, moving distally through the gut?
How is the microbiota composition determined?
Becomes more diverse with more bacteria overall
Oxygen availability, antibiotic use, diet, environment, immune regulation
What are the four main anaerobic genera seen in the intestinal microbiota?
What are the four main aerobic genera?
How does absence of a microbiota affect immune development?
Microbiota allows the immune response to develop
- lymphocyte infiltration
- increased antibody diversity
- increased B cell response
- decreased mature lymphatic tissue
How do SCFA regulate the immune response?
- commensal bacterias produce SCFA
- SCFAs regulate PMNs, dendritic cells, and macrophages
- if pathogens expand, killing commensals, SCFA decreases, activating immune system
How does the microbiota protect against C. difficile?
Competes for nutrients and space; C diff typically only occurs following antibiotic use
How does the microbiota help to regulate digestion?
- Mediates bile acid synthesis
- lipid absorption
- amino acid metabolism
- vitamin synthesis
- SCFA production
What diseases/conditions might be caused by microbiota imbalances?
- Inflammatory Bowel Disease
- Crohn's Disease
What bacterial shift is seen in inflammatory bowel disease patients?
Shift from obligate anaerobes to facultative anerobes
(specifically from bacteroides to proteobacteria)