MichaelsMucosal Immunity Flashcards
What are the defenses involved in innate immunity
mucins, epithelial cells, defensins
What are the actions of adaptive immunity
antigen presentation, humoral, T cells
Describe the lamina propria in the GI system
size depends on antigenic environment
Describe antigen presenting cells in GI system
chief APCs are dendritic
Macrophages abundant
Describe role of mast cells in the GI system
contribute to local host defense by producing important mediators of inflammation
Induce chemoattraction of inflammatory cells to mucosal tissues
What is the function of Goblet cells in GI track
mucus secreting- acts as a barrier function and antibacterial
What is the function of epithelial cells in innate immunity in the GI
barrier and antibacterial. release chemokines and cytokines
What is the role of paneth cells in the GI track for innate immunity
antibacterial secreting cells
What is the role of M cells in innate immunity of GI
antigen sampling
What are GI mucins made of
O0linked oligosaccharides
What structures are found on the GI mucins
glycocalyx
Why is there regulated expression of TLRs and Nod like R in the GI
so it is biased toward anti-inflammatory responseā>limits inflammation in GI
What are defensins
small cationic peptides that contain three intra chain disulfide bonds
Where are alpha defensins produced
small bowl by paneth cells and neutrophils
Where are beta defensins produced
colon by absorptive epithelial cells
What are involved in adaptive immunity of GI
humoral immunity and IgA
Th17 dominant cell-mediated immunity
Suppression of cell-mediated immunity
What is the lymph specialization in GI
peyers patches
What is the role of M cells in general
pinocytose and transport to express MHC class II, not APCs
What areas do M cells transport material to
follicular dome and interfollicular
What are the 4 ways of Ag capture in mononuclear cells
nonspecific transport, FcRn-dependent transport, Apoptosis-dependent transfer, Ag capture
What is the role of mucins
sequester bacteria to prevent transfer across barrier
Where are paneth cells found
in the crypts of epithelium
Where are peyers patches located
directly under epithelium, have T B cells and APCs
Where are dendritic cells in GI
stretch branches into lumen and also can travel via lymph channels
Where does Antigen presentation take place in GI
mesenteric lymph node
What do plasma cells make in GI
IgA
How do NLRs and TLRs locate bad material
pattern recognition
Where are NLRs ad TLRs
lamina propria -TLRs
epithelial cells- NLRs
What is the first step to initiate immune response in GI
peyers patches Ag presentation
How do antigens get to the peyers patches
M cells
How can you differentiate M cell from epithelial cell
do not have cilia
What does the dendritic cell activate
T cells
What do the GI dendritic cells express
IL6 and TGFbeta
What do the T cells in GI produce
IL 17 and IFN gamma
What is the name for the cells that help dampen inflammation in GI
T reg cells called FoxP3
People who lack Foxp3 have what problem
chronic gut inflammation
What type of Dendritic Cells are CD103
the regulatory DC
what is the role of alpha 4 beta 7 and CCR9 on T or B cell
homing so that the cell can get back to lumen, bind MadCAM and CCL25
Chemokine R CCR9 is in SI or colon
SI
CCR10 is found where and binds what
colon and binds CCL28
what promotes expression of alpha4beta7 and CCR9
retinoic acid
What is the function of IgA
protective, neutralizes biologically active Ag
prevents uptake of Ag by GI tract
inhibits bacterial adherence
enhances innate immune factors
What form is serum IgA
very low levels. found monomeric
What is important about IgA that makes it anti-inflammatory
does not bind to Cā
prevents colonization without inflammation
How do B cells switch to IgA
presentation from Activated T cell in presence of NO and TGFbeta which is secreted by DC
Describe T cell independent class switch
through TLR cause DC to release APRIL, TGF beta and BAFF which cause B cell to class switch to IgA
Describe transport of IgA
unidirectional
Describe components of cell-mediated immunity
intraepithelial cells are mostly CD8 Tcells
gammadelta T cells
intraepithelial cells have limited T cell repertoire
Lamina propria cells are what type T cells
CD4+ T cells
What are the CD4 subsets
Th17
Th2
What is the role of Th17 cells
colonization and protection of gut
release IL-17 and IL-22
What is the role of Th2 cells
Th2 cells protect against helminthic infections
What are the characteristic cytokines of Th2
IL4 and IL13
overactive Th17 is seen in what disease, or thought to be
crohns
Which area has the highest percentage of Fox P3 T regs
lamina propria
What molecules are key in the devlopment of Tregs
CD103 DC, retinoic acid, TGFbeta
What are the characteristic cytokines with the FoxP3 T regs
TGFbeta, IL10 and IL2
What is inflammatory bowel disease
Crohns, affects entire thickness of bowel wall and sometimes terminal ileum
Ulcerative colitis- colonic mucosa
What is celiac disease
gluten sensitivity
activation of Th2 cells, B cells and Tregs
inflammation
What else can cause immune response by gut
food allergy and tumor develoment from prolonged immune responses
What can cause dysregulation of innate immune response in inflammatory bowel disease
defective defensin expression, inadequate feedback regulation
What can cause abnomral cell mediated immunity in IBD
overactive Th17 and granulomatous inflammation by IFNgamma producing Th1 cells
What can cause defective regulatory T cell function in IBD
FoxP3 and IL2 or IL2R deficiencies resulting in IBD
What is the 4th abnormality in IBC
defective autophagy
What Ab are key in celiac disease
anti endomysium IgA, anti tissue transglutaminase IgA, anti gliadin IgA and anti-gliadin IgG
What is celiac disease mediated by
T cells
What other autoimmune disease is celiac assoc with
type I DM and thyroid autoimmune
what are clincial symptoms of celiacs
abdominal pain, diarrhea, growth failure, anemia, osteoporosis or even asymptomatic
What Ig mediates food allergies
IgE type I Hypersensitivity
what are types of food allergies
milke eggs etc. can be outgrown because mucosal barrier not complete till 4 yrs old
What can cause innappropriate digestion
longer peptides, immunogenic, diet, drugs, toxins
why do we think food allergies exist
hygiene hypothesis
symptoms of food allergies
gas, bloating, dirrhea, constipation, urticaria, mimic many other GI disorders, rhinoconjuctivitis, oral allergies and sensitivities (migraines)
Tx for food allergys
no cures, diets, and avoid certain food
