Gut Immunology Flashcards
What is Microbiota?
Microorganisms at a particular site
The microbiota in the intestines influences the result of either _______ or ________
Symbiosis or Dysbiosis
What is Symbiosis?
Immune tolerance, homeostasis and healthy metabolism
What is Dysbiosis?
Immune, intestinal and metabolic disease
What is GALT?
Gut-associated lymphoid tissue
What does GALT consist of?
Peyer’s patches and isolated lymphoid tissue (ILT)
What is critical for the development of GALT?
Microbiota and immune system cross talk
When does GALT finish developing in a human?
After birth and after exposure to bacteria
What in turn regulates the microbiota?
GALT and ILT once they are developed
AMPs (antimicrobial peptides) contribute to?
Mucosal host defense in the GI tract
What type of AMP functions in innate immunity?
Defensins
What type of cells influence production of AMPs?
Enterocytes, paneth cells and colonocytes
What will you find in the outer mucous layer of the intestinal epithelium?
Bacteria
What will you find in the inner mucous layer of the intestinal epithelium?
AMPs
Mucin
Secretory IgAs (SIgA)
Job of secretory IgAs?
Control a peaceful bacteria - host environment
The inner mucous layer is _____ to bacteria due to _____
IMPERMEABLE to bacteria due to Defensins!
If bacteria penetrates the inner mucous layer and the epithelium, it will be picked up by?
Dendritic cells
Describe the adaptive immune system that takes over if bacteria is picked up by dendritic cells in the intestines
- The DC will take the bacteria to a mesenteric lymph node and present it to a naive T cell
- As the T cell begins to differentiate, stromal cells will release TGFbeta to them
- This combined with little cytokines being released results in the naive T cell differentiating into a Treg cell
- Tregs will suppress the immune response, keeping it local and not involve systemic circulation!
What 3 things can have major effects on the gut microbiota?
Changes in diet
Environmental factors
Genetics
Changes in diet or environmental factors may cause?
Dysbiosis - inflammation and immune dysregulation
SCFAs
Short chain fatty acids
Give 3 examples of SCFAs
Acetic acid
Butyric acid
Propionic acid
What produces SCFAs?
Bacteria fermenting undigested dietary carbohydrates
Why are SCFAs important?
Stimulate production of mucous AND
support effective IgA mediated response to gut pathogens
What is food tolerance?
No response to ingested food antigens
A large number of lymphocytes will have receptors for self and for food. NORMALLY how are deleterious immune responses prevented?
Central tolerance
- Developing T/B cells are eliminated in the thymus or bone marrow if they are found to be self reactive
Since intestinal antigens NEVER reach the thymus, central tolerance will not protect against such Ags. How does our body ensure food tolerance?
PERIPHERAL tolerance = ORAL tolerance!
3 main things that control the oral tolerance?
Macrophages
Dendritic cells
T Reg cells
What is oral tolerance?
The extra layers of peripheral tolerance against food antigens so that a deleterious immune response is not initiated because of lack of central tolerance
2 types of food adverse reactions
- Non-immune-mediated
2. Immune-mediated
Non-immune mediated food adverse reaction means?
Absence of an enzyme needed to fully digest the food (food tolerance)
Immune-mediated food adverse reaction means?
Specific immune response that occurs on exposure to a given food (food allergy)
What is the most common type of immune-mediated food adverse reaction?
Type 1 hypersensitivity
Type 1 hypersensitivity is an immune response mediated by?
IgE
If _____ is broken, you may end up with a food allergy
Oral tolerance
Describe the order of events for an IgE-mediated food allergy
- Primary (first) exposure to allergen
- Adaptive immune response makes IgE
- IgE enters circulation and bound to mast cells - Subsequent exposure to allergen
- IMMUNE RESPONSE
Systemic immune response mediated by?
Histamine
Local immune response mediated by?
PAF and Serotonin
Systemic immune response leads to?
Anaphylaxis
Local immune response leads to?
Diarrhea
T reg cells produce ________ that may inhibit mast cell activity and reduce IgE synthesis
IL-10 and TGFbeta
For a food allergy, what cell type activation is bad?
Mast cell
Vitamins ___ and ___ and folate _____ inflammatory response
A and D suppress response
______ promotes inflammation
High fat diet
Best ways to test for Type 1 hypersensitivity to food allergens?
Skin prick test and HISTORY
What is an example of an IgE-mediated allergy?
Wheat
____ may induce the immune response after ingesting wheat
Exercise
Describe how exercise or aspirin can cause an allergic attack?
Exercise or aspirin INCREASE absorption of undigested immuno-reactive allergies into circulation
What is an example of a non-IgE-mediated allergy?
Cow’s milk
How long do non-IgE-mediated allergies take to show a reaction?
up to 48 hours
What is an example of a mixed IgE-mediated food allergy?
Peanuts
What 3 things are activated in a mixed IgE-mediated food allergy?
IgG1 IgE = main contributor ofcourse Complement activation (c3a)
What 2 molecules that are released from either macrophages and mast cells cause anaphylaxis?
PAF - macrophage release
Histamine - mast cell release
What is celiac disease?
Permanent sensitivity to GLUTEN
What genetic components MUST be present to diagnose celiac disease?
HLA-DQ2 AND DQ8
Serous autoantibodies present against _____ enzyme with celiac disease
TG2
In celiac disease gluten peptides are left ______
completely UNdigested
