Mucosal immunity and disease (Michels) Flashcards
M cells
antigen sampling
part of innate immunity
what are the characteristic cytokines of the regulatory response
TGF-β, IL-10, and IL-2
IPEX
symptoms?
genotype?
what immunoglobulin is elevated?
condition where foxp3 are deficienct- chronic inflammation of gut due to lack of regulatory T cells
Arises due to mutations in the transcription factor Foxp3
The phenotype in humans results in a loss of functional Treg cells
Lack of T cell inhibitory activity results in widespread autoimmunity- associated with type I DM
Symptoms include intractable watery diarrhea, failure to thrive, dermatitis, and autoimmune diabetes
Immunoglobulin levels are normal with the exception of IgE which is elevated
Loss of regulatory cytokines
overactive cell-mediated immunity in the gut is a primary response of what
TH17 overactive
granulomatous inflammation by IFN-yproducing TH1 cells
how does induction of oral tolerance occur?
Antigens are taken up in the gut
presented to T cells by CD103+ DC (regulatory DC)
dendritic cell secretes TGF-beta and retinoic acid (both needed for tolerance)
these two mediators induce FOXP3 (T-reg) cell to become tolergenic to normal flora
explains the events in immediate hypersensitivity of food allergies
first exposure to allergen
activate TH2 cells and stimulate IgE class switching in B cells
B cells make IgE antibodies to the allergen and secrete IgE Ab’s
IgE binds to receptor on mast cell
eat the food again–> 2nd exposure to allergen
IgE antibodies cross-link on the mast cell surface and activate mast cells to secrete mediators
vasoactive amines lipid mediators in the hypersensitivity rxn occurs minutes after exposure
Cytokines- late phase reaction (2-4 hrs after exposure)
what are the symptoms of food allergies
vomiting, diarrhea, pruitis, urticaria, anaphylaxis
route of entry is oral
what is the HLA type in celiac disease
HLA-DQ2 or HLADQ8
3-5% of DQ2/DQ8 individuals develop Celiac disease
what is celiac and what other diseases is it associated with
Celiac disease is an immune-mediated disease mediated by T cells
Autoantibodies aren’t pathogenic
Type 1 diabetes, autoimmune thyroid
trigger is gluten (found in wheat, rye, barley)
what are the clinical symptoms
Clinical symptoms can vary from abdominal pain, diarrhea, growth failure, anemia, osteoporosis, or asymptomatic
identify the mechanism of T cell activation and enterocyte destruction in celiac disease
Gluten peptides are taken up/absorbed and transferred into the lamina propria layer
deamination rxn by tissue transglutaminase (TG)- makes peptide negatively charged
deamidation creates a negative charge on specific aa residues to better fit in HLA-DQ pockets (for better presentation to T cells)
T cell interacts with B cells to produce either Anti-gluten antibodies or anti-TG antibodies
T cell can transform into TH1 cell –> leading to villous atrophy and destruction of epithelial cells
Intraepithelial lymphocytes are seen in damaged villous
IL-15 may be involved in enterocyte killing
What are the antibodies in celaic diseaes
IgAto tissue transgluatminase or Gliadin
Check IgG if the pt has IgA deficiency
what is the MARSH score
atrophy damage rises proportionately to the number of tissue transglutaminase antibodies present
levels above 0.6 –> lead to atrophy of villous
what is the job of Treg cells and IgE production
Treg cells and IgE production
Suppress Th1 and Th2 cytokines
Suppress IgE by inducing IL-10 and TGF-β
IL-10
suppresses IgE production
