SM_141b: Mucosal Immunology Flashcards
___ is the largest collection of immune cells in the human body
Gastrointestinal associated lymphoid tissue (GALT) is the largest collection of immune cells in the human body
Gut immune system acts as a ____ environment
Gut immune system acts as a tolergenic environment
- Lots of food, absorbs lots of protein, microbiota
Mucosal immunity is a state of balance between ____ and ____
Mucosal immunity is a state of balance between tolerance and defense
- Tolerance: commensal bacteria and food antigens
- Defense: invading pathogens and toxins
Breakdown in a mechanism of GALT is associated with ____
Breakdown in a mechanism of GALT is associated with disease (e.g. inflammatory bowel disease)
GALT has ____ and ____ site
GALT has inductive and effector site
Structure-function relationships in the GALT include ____, ____, and ____
Structure-function relationships in the GALT include antigen sampling, innate and adaptive immunity, and protective mechanisms such as Paneth cells
Unique aspects of the GALT include ____, ____, ____, and ____
Unique aspects of the GALT include microfold cells, preferential production of secretory IgA, Paneth cells, and promotes immune tolerance to oral antigens
Host defenses in the GI tract include ____, ____, ____, and ____
Host defenses in the GI tract include physical barrier, antimicrobial compounds, specialized immune responses, and indigenous microbiota
Intestinal barrier of GALT includes ____, ____, ____, and ____
Intestinal barrier of GALT includes mucus layer, secretory IgA antibodies, epithelial cells, and intraepithelial lymphocytes
Describe the physical barrier of GALT
Physical barrier of GALT
- Goblet cells produce mucin (Muc2 most abundant) and trefoil factors create highly viscous mucus layer that excludes luminal bacteria
- Defects in mucin production / breakdown of the mucus layer are associated with increased intestinal permeability and inflammation
____ is found in the large intestine and preferentially binds to flagellated bacteria
Lypd8 is found in the large intestine and preferentially binds to flagellated bacteria
___ is the most abundant antibody isotype in the serum and mucosa sites
IgA is the most abundant antibody isotype in the serum and mucosa sites
- Contributes to maintenance of intestinal epithelial barrier function
- Requires epithelial pIgR expression and transcriptional regulation of J-chain production
Describe functions of IgA
IgA functions
- Confines commensal bacteria to the mucus layer of the intestinal lumen
- Binds to invasive pathogens
- Neutralizes microbial toxins and other inflammatory microbial products
- Neutralization of antigens and pathogenes in epithelial cell endosomes
- Uptake of luminal antigens
- Transport of antigens from the LP into the lumen
Selective IgA deficiency may influence the development of ____ and ____
Selective IgA deficiency may influence the development of autoimmunity and allergy
Paneth cells secrete ____, while goblet cells secrete ____
Paneth cells secrete antimicrobial peptides, while goblet cells secrete trefoil peptides (antimicrobial)
There are no Paneth cells in the ____
There are no Paneth cells in the large intestine
GALT accomplishes antigen uptake at the ____
GALT accomplishes antigen uptake at the induction site
- M (microfold) cells
- Peyer’s patches
- Dendritic cells
- Epithelial cells
- MHC class II
- Neonatal Fc receptor expression
GALT has ___ cells and samples luminal antigens
GALT has M (Microfold) cells and samples luminal antigens
GALT accomplishes lymphocyte trafficking via ____, ____, and ____
GALT accomplishes lymphocyte trafficking via inductive sites, migration to mesenteric lymph nodes, and effector sites
- Inductive sites: luminal antigen sampling at Peyer’s patches
- Migration to mesenteric lymph nodes
- Effector sites: re-circulation back to gut (reside in lamina propria)
GALT sites of immune induction include ____, ____, ____, and ____
GALT sites of immune induction include Peyer’s patches, mesenteric lymph nodes, isolated lymphoid follicles, and cryptopatches
- Antigens transported by EC and captured by DC are presented to naive T and B cells inducing their activation, proliferation, and differentiation
____ is an important site for IBD therapy (vedolizumab)
a4B7 is an important site for IBD therapy (vedolizumab)
(binds MADCAM-1 expressed by mucosal endothelial cells)
Following activation, effector cells selectively upregulate ____ and ____ for homing to the GIT mucosa
Following activation, effector cells selectively upregulate chemokine and adhesion molecules for homing to the GIT mucosa
- a4B7
- CCR9
GALT effector cells include ____ and ____
GALT effector cells include lamina propria cells and intraepithelial lymphocytes
Expansion in intraepithelial lymphocytes is part of the pathologic diagnostic criteria for staging ____
Expansion in intraepithelial lymphocytes is part of the pathologic diagnostic criteria for staging celiac disease
Epithelial cells function as part of immunity by expressing ____ for the ____ expressed by bacteria / viruses
Epithelial cells function as part of immunity by expressing pattern recognition receptors (PRR) for the pathogen associated molecular patterns (PAMPs) expressed by bacteria / viruses
GIT epithelial cells recognize microbes binding to ___
GIT epithelial cells recognize microbes binding to PRRs
- Engagement by PAMPs triggers intracellular signaling cascade
- Subsequent gene transcription and production of cytokines and chemokines
- Recruit immune cells to fortify the EC response and limit microbial expansion or invasion
- Responding immune cells from the GALT include innate effectors and adaptive effectors
Intestinal epithelial cells orchestrate immunity via ____
Intestinal epithelial cells orchestrate immunity via microbiome
Oral tolerance is ____
Oral tolerance is induction of mucosal and systemic non-responsiveness to luminal antigens (food and microbial)
Oral tolerance must be ____ and ____
Oral tolerance must be developed and maintained
- Developed: grow tolerant to food allergy
- Maintained: changes in microbiome lead to loss of tolerance
Describe distinct subsets of dendritic cells
Distinct subsets of dendritic cells
- CD 103+ promote oral tolerance
- CD11b+ promote oral tolerance but can also be pro-inflammatory
- Wnt-B-catenin signaling regulates the balance between inflammation vs regulatory reesponses in the gut
___ influences mucosal immunity
Enteric nervous system influences mucosal immunity
Majority of bacterial species in GI tract are ____
Majority of bacterial species in GI tract are non-culturable
Immune tissue development requires ____
Immune tissue development requires normal gut colonization
Critical interactions of the ____ and ____ occur in normal homeostasis
Critical interactions of the microbiota and mucosal immune system occur in normal homeostasis
___ describes the intestinal flora when it has been altered from a healthy equilibrium or baseline
Dysbiosis describes the intestinal flora when it has been altered from a healthy equilibrium or baseline
Dysbiosis contributes to development of ____, ____, ____, and ____
Dysbiosis contributes to development of IBD, diabetes, metabolic syndrome and obesity, and food allergy
Describe relationship between dysbiosis and IBD
Relationship between dysbiosis and IBD
- Human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles
- A large number of susceptibility genes have been identified in IBD: Atg16L1
Neontal antibiotic exposure alters commensal microbiota and enhances ____
Neontal antibiotic exposure alters commensal microbiota and enhances food allergen sensitization
____ containing microbiota protects against sensitization to food allergens
Clostridia-containing microbiota protects against sensitization to food allergens
- Clostridia-containing microbiota activates protective immunity
____ useful in patients with recurrent C. difficule colitis
Fecal microbiota transplantation useful in patients with recurrent C. difficule colitis
