Microbiota Flashcards
Paneth cell anti-microbial peptides
Alpha-defensins Lysozyme C Phospholipase A2 RegIII-gamma Cryptdin relates sequences (CRS)
Disrupt membrane integrity of microbes
alpha-Defensins
Hydrolyzes peptidoglycan in bacterial cell wall
Lysozyme C
Catalyzes hydrolysis of fatty acids in cell membrane
Phospholipase A2
Binds peptidoglycan, bactericidal against Gram-positive bacteria
RegIII-gamma
Antibacterial activity comparable to cryptdins
Cryptidin related sequences (CRS)
What are some of the pathogens strategies for evasion of AMPs?
Surface charge modification Capusle formation Modulate AMP expression Efflux pumps Protease secretion
What are some of the biological activities of IgA?
Inhibition of adherence Mucus trapping Virus neutralization Enzyme and toxin neutralization Inhibition of antigen penetration
What are some ways microbes evade IgA?
Specific IgA proteases (meningitis assocation)
Other proteases (Porphyromonas gingivalis, Enterbacteriaceae)
Glycosidases (IgA heavily glycosylated and subject to damage)
IgA binding proteins
What are the 3 major classes of bacteria that exist in a healthy, balanced microbiome?
Symbionts: mutual relationship with known health promoting functions
Commensals: permanent resident, no benefit or harm
Pathobionts: calmness but have potential to induce pathology
Name some diseases associated with an altered microbial composition?
IBD Autoimmunity Obesity Diabetes Asthma and allergy Colorectal carcinoma
What are some factors that influence microbial composition of microbiota?
Non-immune factors: oxygen tension, pH, digestive enzymes, bile salts and mucus
Immune factors: defensins, IgA
Proposed mechanisms: create environment, provide selective nutrients, produce discriminating antimicrobials
How does oxygen tension change microbiota composition?
Increased oxygen tension is associated with increased abundance of facultative anaerobic bacteria
What role does the intestinal microbiome play in immune development?
Without bacterial colonization you get underdevelopment of lymphatic tissues, delayed B cell migration, reduced antibody diversity, reduced lymphocyte responsiveness
How do commensal bacteria help with the production and function of short chain fatty acids (SCFAs)??
Commensal bacteria ferment non-digestible dietary polyssarcharides to produce SCFAs – which regulate PMNs, dendritic cells, macrophages/monocytes, and intestinal epithelial cells; induce regulatory T cell differentiation; and regulate expression of virulence factors on bacterial pathogens
How do microbiota contribute to host protection?
They prevent pathogen colonization by:
- bacteriocin production
- SCFA production
- Consumption of oxygen
- Competition for nutrients
- Competition for attachment sites
- Induction of epithelial antimicrobials
- Induction of mucus production and secretion
Explain how antibiotics may contribute to C. diff infection?
Antibiotics kill many of the commensal bacteria that colonize the colon –> C. diff gains a foothold and produces toxins that cause mucosal injury –> Neutrophils and RBCs leak into gut between injured epithelial cells
How do commensal bacterial regulate digestion?
They mediate bile acid synthesis, lipid absorption, amino acid metabolism, vitamin synthesis and SCFA production
Byproducts of commensal fermentation (metabolites) regulate the immune system
What are some intestinal microbiome-disease associations?
Inflammatory bowel disease (Crohn’s)
Obesity and obesity related diseases (Diabetes, non-alcoholic fatty liver disease)
Cancer
Allergy/Asthma
Explain how IBD is associated with microbiota.
IBD patients have abnormal bacterial colonization and immune function
Characteristic shift in microbial colonization from obligate anaerobic bacteria to facultative anaerobic species (proteobacteria) – associated with increased oxygen tension caused by inflammation
What is a probiotic?
A viable microbial food supplement which beneficially influences the health of the host – improves intestinal barrier function, stimulates mucin secretion, stimulates antimicrobial peptide expression, enhances IgA production, anti-inflammatory activity
How are probiotics being used in the treatment of immune disorders?
Restoring a healthy biota
Restores barrier function
Skew T cell immune responses to Th1 type
