Gut Immunity, Nutrition, and adverse food reactions

Question 1

What is the most abundant Ig in the body?

Answer 1

IgA

-IgG would be the answer for blood

Question 2

With an allergy which part of the immune system gets activated?

Answer 2

the adaptive part.

-the innate part always responds anyway

Question 3

When we have a food allergy, what got knocked out?

Answer 3

oral tolerance

Question 4

Which cells are important for oral tolerance?

Answer 4

iTreg cells

Question 5

Describe the process of oral tolerance

Answer 5

We get the ag from with a dendritic cell, it goes to the mesenteric lymph node where it sees t cells and releases TGF-B, RA, and IDO to make Treg cells, they go to the epithelium and expand
-we always make plasma cells that secret a lot of IgA and that also goes back to the epithelium

Question 6

Where are Ag’s captured in oral tolerance?

Answer 6

the lamina propria

Question 7

What to DC’s use to induce IgA secreting plasma cells?

Answer 7

RA

Question 8

How are gut-homing iTregs expanded in the lamina propria?

Answer 8

by IL-10 expressing macrophages

Question 9

What do the iTregs do then?

Answer 9

they can suppress the systemic immune responses, including allergic sensitization, in an Ag-specific manner

Question 10

What does Vit D, A, and folate do?

Answer 10

suppress inflammation

Question 11

What does a high fat diet do?

Answer 11

promotes inflammation

Question 12

How does the gut microbiota suppress allergic immune responses?

Answer 12

through the induction of Treg cells

Question 13

What is involved with the effector mechanisms in allergies?

Answer 13

IgE and basophils and mast cells

-microbiota suppress basophils and mast cells

Question 14

What specifically do iTregs suppress?

Answer 14

Th2 cells

-these are central to generating IgE and allergic effector cells

Question 15

What is food allergy caused by?

Answer 15

Ag-specific immune response that occurs reproducibly on exposure to a given food

Question 16

What are the two groups of immune reactions of food allergies?

Answer 16

IgE mediated and non

Question 17

What are non-IgE mediated reactions mediated by?

Answer 17

T-cells (type 3 or 4 hypersensitivity)

Question 18

after the first 3-5 years, what do most of us lose our sensitivity to?

Answer 18

milk, eggs, wheat, and soy

Question 19

What allergies continue into adulthood?

Answer 19

peanuts, treenuts, fish, and shellfish allergies

Question 20

What Th2 cytokines are GI manifestations of food allergy dependent on?

Answer 20

IL-4, 13, and 9

Question 21

What is anaphylaxis?

Answer 21

a reaction resulting from sudden release of multiple chemical mediators as a result of events mediated by IgE Ab’s
-it affects a lot of things

Question 22

With the peanut allergy, what cytokines did the Th2 cell secrete to make B-cells make a bunch of IgE?

Answer 22

IL-4, 5, and 13

Question 23

What are mast cells activated by in the nut-mediated allergy?

Answer 23

IgE cross-linking the FceRI

-can also be mediated by IgG1-induced activation of Macs

Question 24

What increases the vascular permeability and smooth m. contractility in the anaphylaxis reaction?

Answer 24

PAF and histamine

-only PAF with the Mac situation

Question 25

What comes out when we increase the vascular permeability?

Answer 25

C3 and C5

Question 26

What cuts C3 and C5?

Answer 26

tryptase released from activated mast cells | -this exacerbates the cymptoms by activating even MORE mast cells

Question 27

What is Wheat allergy?

Answer 27

a classic food allergy | -IgE plays a central role

Question 28

What are the 6 causes of food interolance that we talked about?

Answer 28

- absence of an enzyme (lactase?) - irritable bowel syndrom - food poisoning - sensitivity to food additives - recurring stress or psychological factors - celiac disease

Question 29

What is celiac disease?

Answer 29

chronic digestive condition is triggered by eating gluten * ppl with this are not at risk of anaphylaxis* - disease of digestive origin basical

Question 30

What is gluten?

Answer 30

a protein found in wheat and other grains

Question 31

What is CD caused by?

Answer 31

-it's a systemic immune disorder caused by a permanent sensitivity to gluten

Question 32

What can CD be associated with?

Answer 32

GI findings... or anything really

Question 33

What antibody is the marker for CD?

Answer 33

anti-tTG2 ab's | -95% of ppl who have CD go undiagnosed because they don't have any symptoms

Question 34

Which 2 molecules are the main genetic predisposing factor for CD?

Answer 34

HLA-DQ2 and DQ8 | -play a key role in orchestrating an adaptive immune response against gluten peptides

Question 35

What auto antibodies are found with this disease?

Answer 35

ab's against the enzyme tissue transglutaminase 2 (TG2)

Question 36

Which cells phagocytose to get the Ag's?

Answer 36

Macs

Question 37

Which cells endocytose to get the Ag's?

Answer 37

DCs and B cells

Question 38

Are there any Ag-free MHC molecules on the APC?

Answer 38

no

Question 39

Why is gluten such a good antigen?

Answer 39

it has a lot of proline which is poorly digested in the small intestine due to lack of prolylendopeptidases - it also has a lot of glutamine - big chunks of it are left undigested

Question 40

What deaminates some of the glutamines on gluten?

Answer 40

TG2 - transglutaminase 2 - makes it charged.... not ours anymore! immune system recognizes it

Question 41

What heterodimer do APC's have that binds the charged glutamine?

Answer 41

P6 of the HLA-DQ2.5

Question 42

What happens after the gluten is presented on those HLA's?

Answer 42

self reactive T-cells are made and then type 4 hypersensitivity happens -chronic inflammatory response as long as patients continue to ingest gluten

Question 43

What 2 ab's are made when an APC presents the deamidated gluten peptide to the helper t cell?

Answer 43

Anti-gliadin ab's and anti-TG2 antibodies

Question 44

Where do gluten peptides react with TG2?

Answer 44

in the subepithelial LAMINA PROPRIA

Question 45

How does the APC present the gluten peptides?

Answer 45

via HLA-DQ2 or DQ8

Question 46

What cytokines do the CD4 T cells secrete to induce the release of MMPs which ultimately results in mucosal remodeling and villus atrophy?

Answer 46

Th1 cytokines such as IFN gamma

Question 47

What cytokine links the adaptive immune system to the innate immune responses?

Answer 47

IL-15

Question 48

How do you test for CD?

Answer 48

-start with measuring IgA ab to human tissue transglutaminase (TTg) -meausrement of total serum IgA can facilitate interpretation hen the tTG IgA is low -

Question 49

What can be used to identify the unusual case of seronegative CD?

Answer 49

and intestinal biopsy

Question 50

What is recommended to confirm the diagnosis of CD in all cases?

Answer 50

and intestinal biopsy

Question 51

When can CD be excluded from our Dx?

Answer 51

if the individual lacks HLA DQ2 or 8 alleles