Gut Immunology Flashcards
What are the components of GALT?
Isolated lymphoid follices (ILFs)
Peyer’s Patches (PPs)
How do PPs and ILFs contribute to the gut immune system?
They lack afferent lympathic vessels so they recieve Ags from DC
Ag-loaded DCs induce differentation of T cells and T cell depedent B-cell maturation
B cells then induce the development of IgA-producing plasma cells
What do paneth cells and epithelial cells produce?
Defensins
IgA is secreted on the surface
How does the IgA maintain a peacful bacteria-host interaction?
IGa does not ativate complement
IgA does not activate phagocytes
IgA is resistant to proteolysis by peptidases
How do defensins interact with the inner mucous layer?
They have a positively charged AA side chain and a hydrophobic AA side chain
How is commensal bacteria regulated?
DC cannot penetrate the systemic circulation
B and T cells leave the mesenteric LNs through the efferent lymph, enter the bloodstream at the thoracic duct and home back to the intestinal mucosa
What is the role of Treg cells in the GI?
Treg cells suppress Th1, Th2, and Th17 responses
Treg produce IL-10 to suppress TH cells
How does diet affect gut microbiota?
Undernutrition leads to a decreased immune function
This leads to an infection with enteropathogens
Leads to impaired absoprtion
This goes back to malnutrition
What do SCFAs do?
They help induce IL-10, induce Tregs, and promote Treg function in order to support an effective IgA mediated response to gut pathogens
How do T-cells contribute to peripheral tolerance?
Some T-cells with high affinity for self-Ags will express the transcription factor Foxp3 and become natural T regulatory cells
What is the mechanism of oral tolerance?
1) Macrophages take up Ags
2) Macrophages transfer Ags to DCs in the LP
3) Ag-loaded DCs move from LP to mLNs
4) DCs stimulate naive CD4+ T cells to induced CD4_ CD25+ Foxp3+ Treg cells
What do DCs release in order to differentiate CD4+ T cells?
Retinoic acid (RA)-directly induces Treg cell differentiation
TGF-B-mediates Foxp3 upregulation in Treg cell differentiation
Indoleamine 2,3-dioxygenase (IDO)-exerts important immunosuppressive functions and induces profliferation of Treg cells
What is the difference between non-immune mediated ARs and immune-mediated ARs?
Non-immune mediated means that you lack an enzyme needed to fully digest a food (ex. Lactose interolerance)
Immune-mediated means that there is a specific immune response upon exposure to a given food (ex. Celiac’s disease)
What is a type I hypersensitivity to food?
Development of IgE against food allergens
What is a type II and Type IV hypersensitivity reaction to food Ags?
Involves activation of macrophages by allergen-Ab complexes in FcyR-dependent manner and activation allergen-specific T cells
Describe a primary allergen encounter
1) Ingested Allergen
2) TH2 response
3) Adaptive immune response by B cells that mature into plasma cells to make IgE to allergen
4) IL-4 –> IgE
5) IgE enters circulation and is rapidly bound by FcRe (CD23) on mast cells in tissues
Describe a subsequent exposure
Cross-linking causes mast cell degranulation that releases:
1) Vasoactive amines
2) Cytokines/chemokines
3) Lipids
Repeated allergen contact activates what?
Allergen-specific T cells and induces IgE-depdent secondary immune response
After allergen ingestion and degradation, allergen fragments are distributed throughout the body so that an allergic response develops in other parts of the body
What are some early allergic reaction mast cell-derived mediators?
Histamine
TNFalpha
Granules such as tryptase, chymase and peroxidase
What are some late allergic reaction mast cell-derived mediators?
Bradykinin and PAF
IL-1,2,3,4,5,6
TNFalpha
What does histamine do?
SM contraction, vascular permeability
What does bradykinin do?
SM contraction, vascular permeability
What does TNFalpha and IL-1 do?
Targets endothelial cells, inflammation
What does IL-5 do?
Sputum eosinophils
What are some environmental factors on allergic sensitization?
Vitamin D, A and folate suppress inflammatory response
High fat diet promotes inflammation
How does a skin prick food allergy test work?
Used to assess type I hypersensitivity
What is the primary tool for assessing immediate hypersensitivity reactions?
History
What is the gold standard for food allergy diagnosis?
Oral food challenge
Explanin Non-IgE-Mediated allergic reactions to peanuts
1) Peanuts can contribute to shock by producing C3a
2) C3a stimulates macrophages, basophils, and mast cells to release histamine and PAF in a C3aR dependent manner
3) PAF and histamine increase vasculary permeability and SM contraction
Give the summary for a nut-induced anaphylaxis
IgE is produced (mostly)
Complement and IgG1 are produced
What are the most important allergens in a wheat allergy?
alpha-amylase inhibitors, germ agglutinin, and peroxidase
How does Food-dependent Exercise-Induced Anaphylaxis work?
Exercise and/or aspirin enhance absoprtion of undigested immuno-reactive allergens into the circulation
What is a cow’s milk allergy?
Non-IgE: Reactions are delayed, no testing needed
IgE: Occurs Immediately, testing required
What is the main genetic predisoping factor of CD?
HLA-DQ2 and DQ8
What is the defining characteristic of CD?
Serum autoantibodies against tissue transgluaminase 2 (TG2)
Majority of CD patients express the HLADQ2.5
What type of hypersensitivity is CD?
Type IV hypersensitivity
What test is no longer recommended for detecting CD?
Anti-gliadin antibody test due to the inferior accuracy
What is the preferred screening method?
tTG-IgA test
