Gut Immunology

Question 1

Homeostasis in gut mucosa is preserved by (2)

Answer 1

Secretory IgA and induced oral tolerance.

Question 2

How do Peyer’s patches and isolated lymphoid tissues receive Ags?

Answer 2

From Ag-transporting DCs. This is because PPs and ILFs do not have afferent lymphatics.

Question 3

MAMPs

Answer 3

Patterns on microbes that bind to PRRs on epithelial cells and DCs.

Question 4

Isolated lymphoid tissues

Answer 4

Single B cell follicles that are inductive sites for IgA production.

Question 5

How do microbes cross the epithelial and enter PPs?

Answer 5

M cells.

Question 6

Which cytokines cause cytotoxicity and delayed type hypersensitivity?

Answer 6

IFN-y

TNF

Question 7

Which cytokines activate neutrophils?

Answer 7

IL-17

TNF

Question 8

What are AMPs and where are they produced?

Answer 8

Antimicrobial peptides.

Epithelial cells

Question 9

What eliminates commensal bacteria? How? (2)

Answer 9

Macrophages by production of IL-10 OR DCs producing IL-6/TGF-beta

Question 10

What cells differentiate once commensal Ags are presented to DCs?

Answer 10

Tregs

Question 11

What cells can upregulate AMPs?

Answer 11

Th17

Question 12

Mucosal firewall

Answer 12

Combo of mucus layer, AMPs, IgA, and Dcs, Treg, Th17 that limit passage of commensals to the GALT.

Question 13

Microbiota in the GI protects against enteropathogenic infection. What can compromise the microbiotic barrier?

Answer 13

Malnutrition

Question 14

3 SCFAs

Answer 14

Acetate
Propionate
Butyrate

Question 15

SCFAs can result in accumulation of:

Answer 15

Tregs

Question 16

PSA derived from B. fragilis acts on Tregs through:

Answer 16

TLR2 to promote Treg function by increasing expression of IL-10 and TGF-b

Question 17

Oral tolerance

Answer 17

Suppression of immune responses to Ags that have been administered orally.

Question 18

Central vs peripheral tolerance

Answer 18

CT: immature lymphocytes specific for self Ag are destroyed, changed, or made into Tregs.
PT: Mature self-reactive cells are anergic, deleted, suppressed.

Question 19

What 3 molecules are of clinical importance in oral tolerance? What do they do overall?

Answer 19

TGF-beta
Retinoic acid
IDO
Induce Treg differentiation.

Question 20

4 Steps in the response to Ags in oral tolerance

Answer 20

1. Mo directly take up Ags.
2. Mo transfer the Ag to DCs.
3. DCs move from lamina propria to mesenteric LN.
4. DCs stimulate naive CD4+ T cells differentiate into FOXP3 Tregs.

Question 21

IgE mediated food reactions constitute what type of hypersensitivity?
Non-IgE (IgA or IgG)?

Answer 21

Type I

Type III or IV

Question 22

What cell type mediates Non IgE food reactions? When does it occur?

Answer 22

T cells

4-28 hrs after eating

Question 23

Tryptase’s role in anaphylaxis

Answer 23

Released from activated mast cells that act on C3 and C5 to locally generate C3a and C5a that further activate MCs and exacerbate the sx.

Question 24

What 3 things can suppress inflammation?

Answer 24

Vitamin D, A folate

Question 25

What is the effect of a high fat diet on inflammation?

Answer 25

It promotes inflammation

Question 26

What cells are suppressed by microbiota?

Answer 26

Basophils, MCs

Question 27

Role of iTregs in allergic sensitization

Answer 27

Suppresses Th2 cells that generate IgE and allergic effector cells.

Question 28

What's the most common food allergy?

Answer 28

Milk

Question 29

How do peanuts contribute to shock?

Answer 29

By causing the production of C3a

Question 30

What does C3a do in anaphylaxis?

Answer 30

It stimulates Mo, basophils, and MCs to produce PAF and histamine, which increase vascular permeability and SM contractility.

Question 31

How are allergies tested?

Answer 31

Skin tests. If it is negative, then it could be followed by an intradermal test.

Question 32

What enables Ags to trigger distal reactions (urticuria, bronchospasm)?

Answer 32

Histamine, PAF

Question 33

GI manifestations of food allergies are dependent on:

Answer 33

Th2 derived cytokines | IL-4, IL-13, IL-9

Question 34

What mediates the local acute GI response to allergen?

Answer 34

PAF and serotonin

Question 35

Major triggers of type IV hypersensitivity

Answer 35

Autoimmunity, environmental Ags, microbial Ags.

Question 36

Type III hypersensitivities are focused around:

Answer 36

Complement activation

Question 37

Why are allergies to cow's milk fairly mild?

Answer 37

There is no known IgE specific for cow's milk protein in human blood. This would cause the prick test to be negative.

Question 38

What type of hypersensitivity is an allergy to cow's milk?

Answer 38

Type IV (delayed type)

Question 39

Peanut allergies have both:

Answer 39

IgE and non IgE mediated mechanisms

Question 40

4 major steps of a nut allergy (food-induced anaphylaxis)

Answer 40

1. MCs activated by IgE and cross-link. 2. Histamine and PAF are released by MCs and cause sx. 3. IgG can induce Mo and neutrophils, which also produce PAF. 4. PAF and histamine increase vascular permeability and SM contractility.

Question 41

B cells and Ag can activate 2 pathways: IgG and IgE. | Which is more severe and what are the 2 subpathways pf IgG?

Answer 41

IgE > IgG IgG can activate complement --> C3a/C5a OR Mo and activate PAF.

Question 42

Silent CD pt's test positive in what?

Answer 42

Anti-TG2 antibodies

Question 43

What 2 molecules predispose a pt to CD?

Answer 43

HLA-DQ2 and DQ8

Question 44

What AAs does gluten have a lot of? | What is the problem with one of them?

Answer 44

Proline and glutamine. | There is no enteropeptidase for proline and is poorly broken down.

Question 45

CD pts express which kind of HLA?

Answer 45

HLADQ2.5

Question 46

What type of hypersensitivity occurs in CD?

Answer 46

Type III

Question 47

Assaying what is most common in clinical practice?

Answer 47

TG2-specific IgA