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GI Exam 1 > GI Immunology > Flashcards

GI Immunology Flashcards

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
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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
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3
Q
  • Food allergies are caused by defects in _ barrier and can affect the _, _, and _ areas of the body
A
  • Epithelial
  • Gut, skin, airways
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4
Q
  • The gut has thin mucosal barriers that are responsible for discriminating between _ and _
A
  • Harmful pathogens
  • Harmless microflora/Diet Ags
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5
Q

Dysbiosis in gut microbiota can lead to:

A
  • Immune disease
  • Intestinal disease
  • Metabolic disease
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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

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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
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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
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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
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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)
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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
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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)
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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
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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
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15
Q
  • What two dietary factors have an impact on gut microflora?
A
  • Intake of fiber
  • Obesity
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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
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17
Q
  • Malnutrition affects the microbiota which functions as a barrier to _
A
  • Enteropathogen infections
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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
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19
Q

Failure to induce food tolerance can result in _ and _

A

Food allergy and Celiac Disease

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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
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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
Q
  • IDO deletion accelerates the differentiation of _ and _ cells and exacerbates colitis
A
  • Th1 and Th17
26
Q
  • What are the two types of immune mediated food allergies?
  • What types of hypersensitivities are these?
  • Are these toxic or non-toxic?
A
  • IgE mediated (Type I)
  • Non-IgE mediated (Type III (IgM or IgG), Type IV (delayed-type/cell mediated))
  • Toxic
27
Q

What are the two subtypes of IgE mediated food allergy reactions?

A
  • Immediate onset
  • Late-phase
28
Q
  • Mechanism of IgE mediated food allergic reaction
A
  • 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
Q
  • Mechanism of non-IgE mediated food allergic reaction
A
  • 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
Q
  • How do mast cells function in non-IgE mediated food allergies?
A
  • 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
Q
  • _ cells are at the center of tolerance to Ags and represent 10% of cells in the lamina propria
A
  • T regulatory
32
Q
  • Dietary factors that suppress inflammation
  • Dietary factors that promote inflammation
  • Microbiota supresses _ and _ cells
  • _ suppresses Th2 cells
A
  • 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
Q
  • Which factor in complement stimulates macrophages, basophils and mast cells?
  • What is produced by mast cells and what is the overall result?
A
  • C3a
  • Histamine and PAF
  • Increase in vascular permeability and smooth muscle contractility

Important in nut-mediated allergies and anaphylaxis reactions

34
Q
  • How are allergies tested?
  • What is the most important factor when determining what a person is allergic to?
A
  • 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
Q
  • 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?
A
  • Histamine and PAF (he repeated this like 10 times, so I would definitiely know it)
  • Serotonin and PAF (leads to diarrhea, vomiting, etc)
36
Q
  • How do anaphylactic reactions affect the following areas of the body:
    • GI tract
    • Airways
    • Blood Vessels
A
  • 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
Q

Anaphylaxis is a reaction resulting from sudden release of chemical mediators as a result of events mediated by _

A
  • IgE
  • Severe itching, hives
  • Swelling of the throat
  • Bronchoconstriction
  • Lowered BP
  • Unconsciousness and sometimes death
38
Q
  • Non IgE mediated food allergies take _ to develop
  • What type of hypersensitivity?
A
  • up to 48 hours
  • IV and III (III shows up a little sooner than IV)
39
Q
  • Type IV non IgE mediated food allergy mechanism of action
A
  • 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
Q
  • Type III non IgE mediated food allergy mechanism of action
A
  • 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
Q
  • 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
A
  • Delayed hypersensitivity type IV
42
Q
  • How do peanut allergies have both IgE and non-IgE mediated mechanisms?
A
  • 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
Q
  • What are some causes of food intolerance?
A
  • Absence of enzyme
  • IBS
  • Food Poisoning
  • Sensitivity to food additives
  • Recurring stress or psychological factors
  • Celiac disease
44
Q
  • 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 _
A
  • HLA-DQ2 and DQ8
  • Gluten
  • Immune mediated enteropathy
  • TG2 (tissue transglutaminase 2)
  • Autoimmunity (15-20% of CD patients will have autoimmune diseases)
45
Q
  • Ag processing and Presenting occurs thru _
  • Protein Ags undergo _ into peptides and are loaded onto MHC Class II molecules and presented to CD4+ cells
A
  • MHC Class II (found on professional APCs)
  • enzymatic degradation
46
Q
  • 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
A
  • Negatively charged glutamic acid residues can result
  • TG2
  • HLADQ2.5; Th1
  • Type IV
  • Autoantigen
47
Q
  • 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 _
A
  • CD4+, IFN gamma
  • Myofibroblasts
  • Gluten, TG2
48
Q
  • What cytokines are important in the Th1 response to CD
  • Which cytokine links the innate and adaptive immune responses?
A
  • IL-18, IFN gamma, IL 21
  • IL-15
49
Q
  • Who should be tested for CD?
A
  • 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
Q
  • Ways to test for CD?
  • Which HLA Class is more affected (HLA DQ2 or HLA DQ8?)
A
  • 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

GI Exam 1 (10 decks)

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