Gut immunology

Question 1

1. Describe the generation of the subsets of helper T cells in a lymph node.

Answer 1

DC–> lymph node where it encounters a Th0 helper cell-> Th0 can then differentiate into any T helper or Treg

Question 2

3. Discuss genetic and environmental contributions to Crohn’s, ulcerative colitis, and celiac disease.

Answer 2

old friends hypothesis- worms–>Tregs
many risk loci for IBD, high association
no difference in Th subgroup involved in IBD subtypes

Question 3

4. Celiacs

Answer 3

HLA-DQ2/8.
–gliadin has lots of prolines. P6 GLUtamic acid has high affinity for HLADQ2
gliadin only fits in HLA DQ2
Th1 and Th17 chronic frusterated immune response
DQ@ also associated with DM1

Question 4

5. Discuss current thought about non-celiac gluten sensitivity

Answer 4

The essential requirements for diagnosis of non-celiac gluten sensitivity:
■ Negative blood tests for celiac disease and no sign of damage on an intestinal biopsy. ■ Symptom improvement when gluten is removed from the diet.
■ Recurrence of symptoms when gluten is reintroduced.
■ No other explanation for the symptoms.
. This syndrome is not HLA-DQ2 or –DQ8 associated, and may be a form or food allergy, though there are no studies of mechanism yet.

Question 5

Th1

Answer 5

INF gamma—> attract M1 macrophages
IL2–>activated CTLs

typical target is TB
activated in RA, T1D, MS

Question 6

Th17 Helper T cells,

Answer 6

are similar to Th1, cause focused inflammation, more powerful than Th1. Listeria, Candida.
They make IL-17.
Dendritic cells can make the IL-23 that pushes differentiation into Th17; a new monoclonal antibody (tildrakizumab) specific for IL- 23 is, in Phase 2 studies, remarkable effective in psoriasis. ►IBD will be next, as IL-23 is considered a central cytokine in Crohn Disease and possibly also ulcerative colitis.

typical target is candida
activated in IBD, psoriasis

Question 7

Type 2 Helper T cells,

Answer 7

Th2—> activate M2 function in walling-off pathogens and promoting healing,
important in parasite immunity if the Th1’s M1 macrophages can’t kill the invader. ►Th2 make IL-4 which attracts not only macrophages but also eosinophils.

typical target is worms,
activated is asthma and allergy

Question 8

Follicular Helper T cells, Tfh,

Answer 8

stimulated by antigen,migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE and IgA antibody subclasses.

Question 9

Regulatory T cells, Treg,

Answer 9

make cytokines (IL-10, TGFβ) that suppress the activation and function of Th1, Th17, and Th2 cells, so they keep the immune response in check. They are part of the Th family.

Question 10

Cytotoxic or killer T cells, CTL

Answer 10

destroy any body cell they identify as bearing a foreign or abnormal antigen on its surface, presented on Class I MHC. They can also make IFNγ which attracts macrophages to eat the cells in which they induce apoptosis.

Question 11

tTreg

Answer 11

self reactive cell that turns other T helpers off

Question 12

In a healthy gut Th0 cells that bind peptide/MHC in presence of TGFBeta turn into

Answer 12

Treg (iTreg)

Question 13

A Th0 cell in the gut that binds peptide/mhc in the presence of TGFbeta and IL-6

Answer 13

Th1, Th2, Th17

Question 14

autoimmune component of celiac

Answer 14

there exists TTG2 self reactive B cells. They arent a big deal becasue there shouldnt be any T cells to help them

TTG2-gliadin hybrid gets stuck together, B cell will then present gliadin, and there is a T cell response that helps B cell make TTG2 response

look at IgA TTG2

episode spreading can cause attack on TTG-3 which is autoimmune and causes herpetiform dermatitis