GI Immunology Flashcards
(50 cards)
1
Q
- Homeostasis in the gut mucosa is normally preserved by _ dependent immune exclusion of Ags and by the suppression of proinflammatory responses by _
A
- Secretory IgA dependent
- Induced Oral Tolerance
2
Q
- What two things does oral tolerance depend on?
- What can promote oral tolerance to food allergens in newborns?
- What happens when there is a defect in oral tolerance?
A
- Microbial components
- Dietary Factors (Fiber, Vitamin A, Lipids)
- Breastfeeding for 4 months (also recommended that babies have natural birth to be exposed to microflora in vaginal canal of mothers)
- Food allergies
3
Q
- Food allergies are caused by defects in _ barrier and can affect the _, _, and _ areas of the body
A
- Epithelial
- Gut, skin, airways
4
Q
- The gut has thin mucosal barriers that are responsible for discriminating between _ and _
A
- Harmful pathogens
- Harmless microflora/Diet Ags
5
Q
Dysbiosis in gut microbiota can lead to:
A
- Immune disease
- Intestinal disease
- Metabolic disease
6
Q
What are the components of GALT (Gut Associated Lymphoid Tissue)?
A
- Tonsils/Adenoids
- Peyer’s Patches
- Isolated Lymphoid Tissue
- Appendix
GALT is the largest immune organ in the body
7
Q
- What is unique about GALT compared to systemic lymph nodes?
A
- Lacks afferent lymphatic vessels nad receives Ags directly from the epitlelial surface and via Ag transporting DCs
8
Q
- _ are sensed by PRRs on DCs and intestinal epithelial cells
- These cells are adjacent to _ and recruit B and T cells
- Recruitment of B and T Cells causes cryptopatches to develop into _
- ILFs are _ that act as an inductive site for _ production
A
- MAMPs (Microbe associated molecular patterns)
- Cryptopatches
- Mature ILFs
- Single B Cell follicles, IgA
9
Q
- Microbes can enter _ thru M Cells
- The microbes are then endocytosed by _ in the subepithelial dome
- _ interact with local lymphocytes to induce T Cell differentiation and T cell dependent B cell maturation
- This induces the development of _ producing plasma cells
- _ IgA is released into the intestinal lumen
A
- Peyer’s Patches
- DCs
- Ag Loaded DCs
- IgA
- Dimeric
10
Q
- Sensing of MAMPs stimulates _ of intestinal epithelial cells and increased density of _ cells
- MAMPs also cause release of _ from intestinal epithelial cells
A
- proliferation, Paneth cells
- AMPs (antimicrobial peptides)
11
Q
- What is required for class switching from IgM to IgA?
- Which cells secrete this?
- What is special about IgA?
A
- TGF Beta
- T Regulatory Cells in lamina propria
- Dimeric and secretable into GI system
12
Q
- Abnormal activation of Th1 and Th17 cells can lead to _
- Abnormal activation of Th2 cells can lead to _
A
- Inflammation/Chron’s (via production of TNF and IFN gamma, IL17)
- Allergy/Adverse Food Reactions (IL4,Il5,IL13)
13
Q
- _ made by Goblet cells is primary barrier limiting contact between microbiota and host tissue
- Epithelial cells produce _ that also play a role in limiting exposure to commensal microbiota
- Translocating bacteria are eliminated rapidly by _ which release _ (immunosuppressive factor)
- Translocating bacteria can also be taken up by _ cells that produce _ and traffic to mesenteric LN
- Presentation of Ags by these cells leads to differentiation of _ cells
- _ cells are also activated and upregulate AMPs to control gut microbiome
A
- Mucus
- AMPs (Antimicrobial Peptides)
- Macrophages, IL-10
- Dendritic Cells, IL6, TGFBeta
- Treg
- Th17
14
Q
- _ % of cells in the lamina propria are T reg cells which help activate _ antibodies
- Treg cells, together with AMPs, IgA, Th17 cells, DCs make up a _
A
- 10%
- IgA
- Mucosal firewall
15
Q
- What two dietary factors have an impact on gut microflora?
A
- Intake of fiber
- Obesity
16
Q
- Balanced microbial composition results in _ and maintenance of homeostasis
- Dysregultion of the immune system and inflammation can be caused by environmental factors and results in _
A
- Symbiosis
- Dysbiosis
17
Q
- Malnutrition affects the microbiota which functions as a barrier to _
A
- Enteropathogen infections
18
Q
-
Role of microflora produced SCFAs in gut homeostasis:
- What are the SCFAs?
- Which type of cells do SCFAs help regulate and by what mechanisms?
A
- SCFAs= acetate, propionate, and butyrate
- Acetate
- Accumulation of IL-10 Tregs
- Butyrate
- Directly acts on Tregs
- Modulates DC function
- Proprionate
- TLR2
- IL10
- TGFBeta
- Stimulate production of mucus by goblet cells
19
Q
Failure to induce food tolerance can result in _ and _
A
Food allergy and Celiac Disease
20
Q
- Central Tolerance
A
- Immature lymphocytes specific for self Ags may encounter these Ags in generative lymphoid organs and undergo:
- Apoptosis
- Changed BCR specificity (receptor editing)
- Development into Treg cells
21
Q
Peripheral tolerance
A
- Mature self reactive lymphocytes are
- Inactivated (anergy)
- Deleted via apoptosis
- Suppressed by Treg cells
22
Q
- _Both central tolerance of T cells and _ differentiation require the interaction of the TCR w. its cognate Ag in the thymus_
- Both of these mechanisms are unsuited for preventing responses against Ags from the intestine and that are not present or expressed in the bone marrow or the thymus
A
- Treg
- This means that there needs to be additional layers of peropheral tolerance to prevent adverse reactions to ingested foods and Ags in the intestine
23
Q
- T cells that have high affinity for self antigen and that express _ will naturally become Tregs
A
- FoxP3
24
Q
- Define steps of oral tolerance
A
- Antigen is taken up by macrophage and transferred via gap junctions to APC (typically dendritic cell)
- This DC migrates to the mesenteric lymph node (which contains T and B cells)
- DCs stimulate Naive CD4+ T Cells to differentiate into Foxp3 expressing T reg cells
- These cells release RA, TGF Beta and IDO
- Induced Treg cells are formed and are able to work in GI mucosa
25
* IDO deletion accelerates the differentiation of _ and _ cells and exacerbates colitis
* Th1 and Th17
26
* ***_What are the two types of immune mediated food allergies?_***
* ***_What types of hypersensitivities are these?_***
* ***_Are these toxic or non-toxic?_***
* **IgE mediated (Type I)**
* **Non-IgE mediated (Type III (IgM or IgG), Type IV (delayed-type/cell mediated))**
* **Toxic**
27
What are the two subtypes of IgE mediated food allergy reactions?
* Immediate onset
* Late-phase
28
* Mechanism of IgE mediated food allergic reaction
* Allergen on DC is presented to a naive T cell
* Th2 cells are induced via Il-4
* IL-4 induces formation of IgE
* IgE antibodies present for that allergen to cause reaction when encountered again
29
* Mechanism of non-IgE mediated food allergic reaction
* Antigen on DC is presented to naive T cell
* Naive T cell secretes various Th2 Type Cytokines (**IL-3, IL-4, IL-5, IL-9, IL-13)** which activate **basophils, eosinophils, and mast cells** leading to allergy symptoms
30
* ***_How do mast cells function in non-IgE mediated food allergies?_***
* **Mast cells release:**
* **Proteases (**rearrange tight junctions)
* **Histamine and PAF** (dilation of capillaries and edema: **increase vascular permeability and smooth muscle contractility**)
* AND **RELEASE OF C3 and C5**
* **Tryptase from activated mast cells activates C3 and C5 to activate even more mast cells (+ feedback)**
* **Cytokines**
*
31
* _ cells are at the center of tolerance to Ags and represent 10% of cells in the lamina propria
* T regulatory
32
* Dietary factors that suppress inflammation
* Dietary factors that promote inflammation
* **Microbiota supresses _ and _ cells**
* **\_ suppresses Th2 cells**
* Vitamin D, A, and Folate (by stimulating iTregs)
* High Fat (HFD) (By stimukating Th2 cells, igE, mast cells, etc)
* Basophils and mast cells
* iTregs
33
* Which factor in complement stimulates macrophages, basophils and mast cells?
* What is produced by mast cells and what is the overall result?
* C3a
* Histamine and PAF
* Increase in vascular permeability and smooth muscle contractility
## Footnote
**Important in nut-mediated allergies and anaphylaxis reactions**
34
* How are allergies tested?
* What is the most important factor when determining what a person is allergic to?
* Skin prick test (take 15-30 min; can do intradermal test if results are vague)
* Blood Tests (To detect levels of IgE Abs in the blood)
* HISTORY
35
* What is secreted by mast cells that causes systemic symptoms of an allergic reaction?
* What is secreted by mast cells that causes local Gi symptoms of an allergic reaction?
* Histamine and PAF (he repeated this like 10 times, so I would definitiely know it)
* Serotonin and PAF (leads to diarrhea, vomiting, etc)
36
* How do anaphylactic reactions affect the following areas of the body:
* GI tract
* Airways
* Blood Vessels
* GI Tract
* Increased fluid secretion
* Increased peristalsis
* Expulsion of GI tract contents via vomiting/diarrhea
* Airways
* Decreased diameter
* Increased mucus secretion
* Blood Vessels
* Increased blood Flow
* Increased permeability
* Inflammation
* Increased lymph flow and carriage of Ag to LN
37
**Anaphylaxis is a reaction resulting from sudden release of chemical mediators as a result of events mediated by \_**
* **IgE**
* Severe itching, hives
* Swelling of the throat
* Bronchoconstriction
* Lowered BP
* Unconsciousness and sometimes death
38
* Non IgE mediated food allergies take _ to develop
* What type of hypersensitivity?
* up to 48 hours
* IV and III (III shows up a little sooner than IV)
39
* Type IV non IgE mediated food allergy mechanism of action
* Major triggers:
* Autoimmunity
* Environmental Ags
* Microbial Ags
* **Tissue injury caused by activation of macrophages**
* **Release of inflammatory cytokines (from CD4+ and CD8+ cells)**
* **Direct target cell lysis and cytokine mediated inflammation**
40
* Type III non IgE mediated food allergy mechanism of action
* Fc receptors on endothelium bind Ab that has reacted with Ag
* Recruitment of more Ab to form larger complex
* Activation of **classical complement pathway**
* Anaphylatoxins C3a, C5a, C4a attract macrophages and neutrophils
* Tissue damage occurs
* Cell lysis
41
* Children who are allergic to Cow's Milk but have no IgE Abs for Cow's Milk and have negative results on skin prick test for CM Ags have _ hypersensitivity
* Delayed hypersensitivity type IV
42
* **How do peanut allergies have both IgE and non-IgE mediated mechanisms?**
* **Food induced anaphylaxis** comes from mast cells being activated by IGE cross linking of FceRI
* Mediators released by mast cells induce symmptoms
* **Nut allergies are also mediated by IgG induced activation of macrophages and neutrophils (so not only is IgE involved, but so is IgG, making this both types)**
43
* What are some causes of food intolerance?
* Absence of enzyme
* IBS
* Food Poisoning
* Sensitivity to food additives
* Recurring stress or psychological factors
* Celiac disease
44
* ***_CELIAC DISEASE:_***
* ***__*****Main genetic predisposing factor**
* **These genes play a role in adaptive response against _ peptides**
* **Hallmark of CD is _ enteropathy that involves innate and adaptive immunity**
* **Which serum Ab is associated with Cb**
* **Strong link between CD and \_**
* HLA-DQ2 and DQ8
* Gluten
* Immune mediated enteropathy
* TG2 (tissue transglutaminase 2)
* Autoimmunity (15-20% of CD patients will have autoimmune diseases)
45
* Ag processing and Presenting occurs thru \_
* Protein Ags undergo _ into peptides and are loaded onto MHC Class II molecules and presented to CD4+ cells
* MHC Class II (found on professional APCs)
* enzymatic degradation
46
* What is special about the degradation of gluten?
* What enzyme is responsible for its degradation?
* _ heterodimer on patient's with CD will create _ cells specific for gluten
* _ hypersensitivity will occur
* TG2 is now an \_
* B Cells now creating anti Tg2 antibodies
* Chronic inflammatory response
* Negatively charged glutamic acid residues can result
* TG2
* HLADQ2.5; Th1
* Type IV
* Autoantigen
47
* Activated _ T cells secrete Th1 cytokines like \_
* This induces release of MMPs by _ resulting in mucosal remodeling and villus atrophy
* Th2 cytokines drive the production of auto-ABs to _ and \_
* CD4+, IFN gamma
* Myofibroblasts
* Gluten, TG2
48
* What cytokines are important in the Th1 response to CD
* Which cytokine links the innate and adaptive immune responses?
* IL-18, IFN gamma, IL 21
* IL-15
49
* Who should be tested for CD?
* Children with:
* Failure to thrive and persistent diarrhea
* GI symptoms
* Non GI symptoms
* Dermatitis herpetiformis
* Dental enamel hypoplasia
* Osteoporosis
* Short Stature
* Delayed Pubery
* Iron deficiency anemia resistant to iron
50
* Ways to test for CD?
* Which HLA Class is more affected (HLA DQ2 or HLA DQ8?)
* Most accurate is intestinal biopsy (can identify unusual case of seronegative CD)
* Measuring IgA Ab to human tissue TTG
* Measuring total serum IgA
HLA DQ2
