Immuno IBD Flashcards
IBD involves 2 disorders that involve?
Chronic Inflammation of the GI tract
Ulcerative Colitis
Chronic inflammation of colon and rectum
Crohns Disease
Chronic inflammation that can occur anywhere along the GI tract (not usually rectum)
What hypothesis explains the increasing incidence of IBD?
Hygiene Hypothesis
Genetics and immune mechanisms both cause IBD. Inappropriate interactions between what things occurs?
Bacteria and immune system
IBD involves increased ______ that causes impairment of GI structure and function
Intestinal permeability
IBD involves increased intestinal permeability. This allows what to cross the mucosal barrier and results in?
Bacteria crosses barrier and (+) innate and adaptive immune responses!
IBD develops due to what 2 main things?
- Dysbiosis - disequilibrium of microbials in normal microbiota
- Mucosal inflammation
IBD develops due to what 2 main things?
- Dysbiosis - disequilibrium of microbials in normal microbiota
- Mucosal inflammation
Which IBD usually involves disruption of barrier function?
Ulcerative Colitis
Which IBD usually involves dysfunction of microbe sensing?
Crohns Disease
What factors are necessary to initiate IBD?
Environmental factors
Environmental factors are necessary to initiate IBD. They act on both?
Genes
Immune system
What is the purpose of normal gut microbiota?
- Protects against pathogens
- Facilitates digestion
- Provides immune survillance
IBD develops in areas of ____ bacterial concentration
HIGH
With IBD, antibodies and lymphocytes are present against ___ antigens
Fecal
What are the 4 main components of microbiome?
- Bacteroidetes **
- Firmicutes *
- Proteobacteria
- Actinobacteria
What are the 4 main components of microbiome?
- Bacteriodetes **
- Firmicutes *
- Proteobacteria
- Actinobacteria
What can control the components of microbiome?
DIET
Dysbiosis of microbiome components causes IBD. Which components of microbiome are altered with Ulcerative Colitis?
INCREASED Proteobacteria
- normally low with normal microbiome
Dysbiosis of microbiome components causes IBD. Which components of microbiome are altered with Crohn’s Disease?
INCREASED Firmicutes and Actinobacteria
Increased Proteobacteria in microbiome?
Ulcerative Colitis
Increased Firmicutes and Actinobacteria in microbiome?
Crohn’s Disease
Diet controls components of microbiome. What type of diets increase normal components?
High protein and High carbs
Diet controls components of microbiome. What type of diets decreased normal components?
High fat
Diet controls components of microbiome. What changes can HIGH fiber make to the microbiome?
INCREASES Bacteroidetes and Actinobacteria
DECREASES Firmicutes and Proteobacteria
Does IBD occur in germ-free environments?
NO
Babies from IBD women have?
Decreased bacterial diversity and altered composition
No specific microbes have been linked to development of IBD. What infections can increased your risk of developing?
Gastroenteritis (salmonella/campylobacter)
No specific microbes have been linked to development of IBD. What infections can decrease your risk of developing?
Helminths colonization
Are mutations associated with the genetic aspect of IBD?
NOOO
= Single nucleotide polymorphisms!!
What genetic changes are associated with IBD?
SNPs
= Single nucleotide polymorphisms
SNPs
Single nucleotide polymorphisms
Alleles that differ at a single base
A common susceptibility locus is found on what chromosome?
16
What susceptibility locus is found on chromosome 16?
IBD-1
What genes does IBD-1 have?
CARD15/NOD2
In what cells are CARD15/NOD2 expressed?
Macrophages and Dendritic cells
CARD15/NOD2 is a?
Pattern recognition receptor
What pattern does CARD15/NOD2 recognize?
MDP = peptide in all bacteria
When CARD15/NOD2 recognize MDP, what do they activate?
NF-KB = INFLAMMATION
SNPs in CARD15/NOD2 then ultimately cause?
(-) of NF-KB and inflammation
= IBD
Somehow defects in CARD15/NOD2 (-) inflammation. How does this actually cause inflammation with IBD?
- Defective Macrophage function
- Defective Epithelial cell responses
- Defective APC conditioning
Somehow defects in CARD15/NOD2 (-) inflammation. How does this actually cause inflammation with IBD?
- Defective Macrophage function
- Defective Epithelial cell responses
- Defective APC conditioning
Defective macrophage function causes?
Chronic T cell stimulation
Defective epithelial cell responses causes?
Loss of barrier
Defective APC conditioning causes?
Inappropriate activation of APCs
SNPs in CARD15/NOD2 then ultimately cause?
(-) of NF-KB and inflammation
= IBD
