Microbiota

Question 1

Paneth cell anti-microbial peptides

Answer 1

Alpha-defensins
Lysozyme C
Phospholipase A2
RegIII-gamma
Cryptdin relates sequences (CRS)

Question 2

Disrupt membrane integrity of microbes

Answer 2

alpha-Defensins

Question 3

Hydrolyzes peptidoglycan in bacterial cell wall

Answer 3

Lysozyme C

Question 4

Catalyzes hydrolysis of fatty acids in cell membrane

Answer 4

Phospholipase A2

Question 5

Binds peptidoglycan, bactericidal against Gram-positive bacteria

Answer 5

RegIII-gamma

Question 6

Antibacterial activity comparable to cryptdins

Answer 6

Cryptidin related sequences (CRS)

Question 7

What are some of the pathogens strategies for evasion of AMPs?

Answer 7

Surface charge modification
Capusle formation
Modulate AMP expression
Efflux pumps
Protease secretion

Question 8

What are some of the biological activities of IgA?

Answer 8

Inhibition of adherence 
Mucus trapping
Virus neutralization 
Enzyme and toxin neutralization 
Inhibition of antigen penetration

Question 9

What are some ways microbes evade IgA?

Answer 9

Specific IgA proteases (meningitis assocation)
Other proteases (Porphyromonas gingivalis, Enterbacteriaceae)
Glycosidases (IgA heavily glycosylated and subject to damage)
IgA binding proteins

Question 10

What are the 3 major classes of bacteria that exist in a healthy, balanced microbiome?

Answer 10

Symbionts: mutual relationship with known health promoting functions
Commensals: permanent resident, no benefit or harm
Pathobionts: calmness but have potential to induce pathology

Question 11

Name some diseases associated with an altered microbial composition?

Answer 11

IBD
Autoimmunity 
Obesity
Diabetes
Asthma and allergy
Colorectal carcinoma

Question 12

What are some factors that influence microbial composition of microbiota?

Answer 12

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

Question 13

How does oxygen tension change microbiota composition?

Answer 13

Increased oxygen tension is associated with increased abundance of facultative anaerobic bacteria

Question 14

What role does the intestinal microbiome play in immune development?

Answer 14

Without bacterial colonization you get underdevelopment of lymphatic tissues, delayed B cell migration, reduced antibody diversity, reduced lymphocyte responsiveness

Question 15

How do commensal bacteria help with the production and function of short chain fatty acids (SCFAs)??

Answer 15

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

Question 16

How do microbiota contribute to host protection?

Answer 16

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

Question 17

Explain how antibiotics may contribute to C. diff infection?

Answer 17

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

Question 18

How do commensal bacterial regulate digestion?

Answer 18

They mediate bile acid synthesis, lipid absorption, amino acid metabolism, vitamin synthesis and SCFA production

Byproducts of commensal fermentation (metabolites) regulate the immune system

Question 19

What are some intestinal microbiome-disease associations?

Answer 19

Inflammatory bowel disease (Crohn’s)
Obesity and obesity related diseases (Diabetes, non-alcoholic fatty liver disease)
Cancer
Allergy/Asthma

Question 20

Explain how IBD is associated with microbiota.

Answer 20

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

Question 21

What is a probiotic?

Answer 21

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

Question 22

How are probiotics being used in the treatment of immune disorders?

Answer 22

Restoring a healthy biota
Restores barrier function
Skew T cell immune responses to Th1 type