Lecture 16: Gut Immunology Flashcards
(38 cards)
Why is the gut microbiota important?
- important to immunity, metabolism, homeostasis
- disruption associated with disease
Why is cross-talk between host gut associated lymphoid tisuse (GALT) and microbiota important?
microbiota regulates GALT/ILT development
GALT/ILT regulates microbiota in turn
What are the main players in GALT?
ILF (isolated/single B lymphoid follicles) and Peyer’s Patches (aggregated lymphoid nodules)
How are pathogens detected in the gut?
Gut microbiota help mature the GALT and mucosa (mutualism)
DCs deliver antigens to GALT + M cells digest microbes and are endocytosed by DCs
After pathogen detection, how is the immune response activated?
- DCs present to local lymphocytes in the gut > TH and Tc activated
- TH cells activate B cells > plasma cells > igA transported to intestinal lumen
- TC cells activate cytotoxic responses
After immune response activation, what structurally happens to the components of gut mucosa?
- MAMPs from microbes activate PRR on intestinal epithelium and DCs > recruit the T and B cells to area > nearby cryptopatches mature into more ILFs
- Epithelial cell proliferates > Paneth cells are formed
What type of cells are found on the intestinal epithelium?
- Goblet cell that produce mucin
- Enterocytes, colonocytes (large intestine) + Paneth cells (small intestine) that produce AMPs, mostly defensins
- Secretory IgA
How does secretory IgA in the intestinal epithelium maintain tolerance against microbiota?
does not activate complement, phagocytes and is resistant to proteolysis
What are the innate responders of the GI tract?
1st line of defense: defensins - have both + charged and hydrophobic ends that form pores, that allow them to penetrate membrane and block pathogen colonization (acts as a barrier)
If the pathogen is able to penetrate the defensin barrier, how does the immune system react?
if pathogen penetrates defensins > attacked by macrophages
If pathogen penetrates the areas with M cells > attacked by macrophages or carried by DCs for presentation to T and B cells in Peyer’s patches or mesenteric lymph nodes
What is the pathway of T cells and B cells that travel via lymph?
thoracic duct > blood stream > venous return to intestinal mucosa
What is the role of TReg’s in GI tract?
if no inflammation, TGF B > naive T cells differentiate into TRegs > inhibit TH1, TH2 and TH17 responses inducing tolerance
What is symbiosis and why is it important?
- balance of microbe composition > affected by diet, environment and genetics
- changes in the above leads to dysbiosis > immune system dysregulation > GI inflammation
How does gut microbiota help the immune system?
How does malnutrition relate to this?
- gut microbes produce short chain fatty acids that influence immune system development
- gut microbiota needs to be nourished to have a nourished immune system (Malnutrition > dysfunctional GI immunity - recurrent infections)
What specific roles does SCFAs produced by gut microbiota play?
-SCFAs are fermented by gut microbiota from undigested carbs
Effects:
- increased IgA and mucus production
- Acetate > increase TRegs and IL-10
- Butyrate > increase TRegs and DCs ability to induce TRegs
- Capsular Polysaccharide A > bind to TLR2 on TRegs to increase IL-10 and TGF-B production
Why doesn’t the GI system react to food?
- oral tolerance to food proteins in the GI tract
- if tolerance is lost we get food allergies and celiac disease
What is the difference between Central and Peripheral tolerance and what mechanisms do immune cells employ to be tolerant?
- happens in the lymphoid organs (deletion, BCR changes, become TRegs by expressing FoxP3)
- main type of tolerance in the GI since gut pathogens not present in thymus to train lymphocytes (anergy, deletion, suppression by TRegs)
How does Oral tolerance develop?
Macrophages take Ags in lumen > lamina propia DC take the Ags > DCs recruited to mesenteric LNs by chemokines > DCs release RA, TGF -B and IDO > T cells induced to be TRegs
What roles do Retinoic acid, TGF B and IDO have in TReg induction to maintain oral tolerance?
Retinoic acid: TReg differentiation
TGF-B: foxp3 expression and Treg differentiation
IDO: inhibits effector T cells and increase TReg proliferation
What is the difference between non immune mediated Food ARs and immune mediated Food ARs?
NIM: lack of digesting enzyme (IBS, food poisoning, stress/psych)
IM: immune response upon exposure to specific food
Celiac disease is what type of food AR? Why?
- immune mediated
- immune response triggered by gluten > GI issues
Immune mediated Food ARs:
Type 1 HS Food AR
Type 3 HS Food AR
Type 4 HS Food AR
IgE mediated:
-IgE vs. food allergens (tested by skin reaction/IgE serum)
Non IgE mediated:
- macrophage activation by food allergen-Ab complex
- allergen specific T cell activation
How does IgE mediated (Type 1) Food AR occur?
1st exposure: primary sensitization
food allergen enters > B cells make IgE against allergin > IgE gets bound to mast cell (sensitization)
2nd exposure: secondary immune response
Allergen binds to IgE on mast cell > cross linking > degranulation of vasoactive stuff (systemic symptoms)
*Anaphylaxis can occur if allergen penetrates GI tract and carried to other systems
What affects the strength of secondary immune response to food allergen in IgE mediated Food AR?
-how much can the allergen penetrate the GI tract > the stronger the allergic reaction
