Tutorial Celiac Disease AI generated

Question 1

Describe the impact of high glucose levels in diabetes patients.

Answer 1

High glucose levels in diabetes patients can lead to glucose spilling over into the urine, causing frequent urination and increased thirst.

Question 2

How can diabetes patients be treated?

Answer 2

Diabetes patients can be treated through immunotherapy, insulin injections based on blood glucose levels, adaption of diet, and physical activity.

Question 3

Explain in layman terms what is wrong with Fenna, according to the content.

Answer 3

Fenna’s immune system destroyed the cells that make insulin, leading to high blood glucose levels, fatigue, frequent urination, and excess glucose in her blood.

Question 4

What is the main trigger for celiac disease according to the content?

Answer 4

Celiac disease is triggered by gluten ingestion in genetically predisposed individuals.

Question 5

Define the hygiene hypothesis in autoimmune diseases.

Answer 5

The hygiene hypothesis suggests that reduced exposure to pathogens due to a hygienic lifestyle may contribute to the rising incidence of autoimmune diseases.

Question 6

How does the hygiene hypothesis explain the balance between tolerance and immune response?

Answer 6

The hygiene hypothesis suggests that exposure to microbes during childhood promotes a healthy balance, while very clean conditions with limited exposure can disturb this balance.

Question 7

Describe the factors implicated in the onset of celiac disease.

Answer 7

Factors include early feeding practices, improved hygiene, time of gluten introduction, amount of ingested gluten, presence of HLA class II genes (HLA DQ2/DQ8), intestinal enteropathy, and elevated serum antibodies (IgA-tTG and EMA).

Question 8

Define villous atrophy.

Answer 8

Villous atrophy is intestinal damage characterized by a reduction in the number of villi, resulting in a flatter surface. This condition can lead to serious nutritional deficiencies.

Question 9

Do you see any similarities between celiac disease and Type 1 Diabetes?

Answer 9

Both diseases have a strong HLA-association. In celiac disease, gluten-specific T cells respond to gluten peptides bound to HLA-DQ2.5 and/or HLA-DQ8, leading to an amplification loop.

Question 10

How are foods containing gluten defined?

Answer 10

Gluten refers to alcohol-soluble proteins found in cereals like wheat, rye, barley, spelt, and kamut.

Question 11

Describe the impact of losing intestinal villi to villous atrophy.

Answer 11

The loss of intestinal villi, responsible for nutrient absorption, can result in severe nutritional deficiencies due to the reduced surface area for absorption.

Question 12

What role do gluten-specific T cells play in celiac disease?

Answer 12

In celiac disease, gluten-specific T cells respond to gluten peptides bound to HLA-DQ2.5 and/or HLA-DQ8, contributing to the autoimmune response.

Question 13

How does the presence of HLA class II genes contribute to celiac disease?

Answer 13

The presence of HLA DQ2/DQ8 genes is associated with celiac disease as gluten-specific T cells respond to gluten peptides bound to these molecules, leading to an autoimmune response.

Question 14

Define the term ‘intestinal enteropathy’.

Answer 14

Intestinal enteropathy refers to the pathological changes in the intestine, often seen in conditions like celiac disease, resulting in impaired absorption and other gastrointestinal issues.

Question 15

Describe the composition of gluten.

Answer 15

Gluten is a complex storage protein found in grains, mainly composed of glutenin polymers and gliadin monomers.

Question 16

What are the unique properties of gluten that make it suitable for dough preparation?

Answer 16

Gluten’s high glutamine content and characteristic amino acid composition.

Question 17

How do gliadin epitopes contribute to gluten-related immune responses?

Answer 17

Gliadin epitopes can trigger host responses, leading to increased gut permeability and immune reactions.

Question 18

Explain the role of the innate immune system in the development of celiac disease.

Answer 18

The innate immune system can be activated by specific gliadin peptides, leading to structural modifications, immune activation, and proliferation of enterocytes.

Question 19

What is the initial step in the process of developing autoimmunity to gliadin?

Answer 19

Partially digested gliadin fragments interact with chemokine receptor 3, leading to the release of zonulin.

Question 20

What happens when gluten immunogenic peptides cross the defective epithelial lining in celiac disease?

Answer 20

They can reach the bloodstream, extend the inflammatory process, and eventually be excreted with urine.

Question 21

Describe the role of tTG2 in celiac disease development.

Answer 21

tTG2 cleaves gluten molecules into gliadin peptides, which attract immune cells, increase intestinal permeability, and induce immune activation.

Question 22

What is the significance of HLA-DQ2 and HLA-DQ8 in celiac disease susceptibility?

Answer 22

Gluten/gliadin modified by TG2 binds to HLA-DQ2 or HLA-DQ8, leading to T-cell activation and immune response.

Question 23

How is celiac disease diagnosed based on antibodies?

Answer 23

Patients with celiac disease have antibodies against tTG2, which is involved in the phagocytosis of gliadin by B-cells.

Question 24

Define the process of T-cell activation in celiac disease.

Answer 24

Gliadin peptides are presented on APCs to T-cells via HLA-DQ2/DQ8, leading to T-cell activation, cytokine production, and B-cell help.

Question 25

What is the role of B-cells in celiac disease pathogenesis?

Answer 25

B-cells phagocytose gliadin bound to tTG2, present it to T-cells, and become plasma B-cells producing anti-TG2 antibodies.

Question 26

Describe the impact of a thymus defect on T-cell recognition in celiac disease.

Answer 26

A defect in the thymus leads to restricted TCR recognition, affecting the peptide recognition part of T-cells in celiac disease.

Question 27

Explain the potential link between pesticides and celiac disease immunity activation.

Answer 27

Pesticides in crops may potentially activate immunity in celiac disease, although this connection has not been definitively proven.

Question 28

What are the consequences of presenting gliadin peptides on APCs to T-cells in celiac disease?

Answer 28

This process leads to T-cell activation, production of IFN-y and IL21, and support to B-cells in the immune response against gluten in celiac disease.

Question 29

Describe the role of HLA in celiac disease pathogenesis.

Answer 29

HLA molecules, composed of alpha and beta subunits, present gluten peptides to APCs through HLA class II molecules, triggering an aberrant CD4+ T cell-mediated immune reaction.

Question 30

Do all individuals with HLA types associated with celiac disease develop the condition? Why or why not?

Answer 30

No, not everyone with these HLA types develops celiac disease due to the polymorphic nature of HLA genes, resulting in different binding motifs and peptide presentation.

Question 31

Define the T cells involved in celiac disease pathogenesis.

Answer 31

CD4+ T cells, also known as T helper cells, play a crucial role in the immune reaction triggered by gluten peptides.

Question 32

How are CD4+ T cells activated in celiac disease?

Answer 32

CD4+ T cells are activated by the post-translational deamidation of gluten peptides by transglutaminase 2, influenced by IL-15 upregulation and presentation of gluten by various immune cells in the lamina propria.

Question 33

Describe the impact of proline residues on gluten epitopes in celiac disease.

Answer 33

Gluten epitopes with more proline residues, like those for HLA-DQ8, are highly resistant to degradation, while the immunodominant DQ8 epitope with fewer proline residues is more sensitive to enzymatic degradation in the GI tract.

Question 34

Explain the process of activation and proliferation of CD4+ T cells in celiac disease.

Answer 34

Activation and proliferation of CD4+ T cells in the lamina propria are induced by contact with gluten, leading to the production of proinflammatory cytokines, metalloproteases, and growth factors, causing cryptal hyperplasia and villous blunting.

Question 35

Describe the role B-cells in celiac disease.

Answer 35

B-cells produce IgM, IgG, and IgA antibodies against tissueglutaminase (t2) and bind to TG2 cross-linked to gluten fragments, leading to enhanced presentation of gluten peptides bound to HLA-DQ on TG2-specific B cells.

Question 36

Define the role of tissue transglutaminase in celiac disease.

Answer 36

Tissue transglutaminase (tTG2) is the autoantigen in celiac disease. It deamidates gliadin peptides, reducing the immunogenicity of gluten and enhancing the binding of gluten epitopes to HLA-DQ, activating gluten-specific T-cell clones.

Question 37

How does the intestinal microbiome potentially influence celiac disease development?

Answer 37

An imbalanced gut microbiome, with more Firmicutes, less Bacteroidetes and lactobacilli, may play a role in the development of celiac disease. Non-pathogenic microorganisms early in life are associated with protection against CD.

Question 38

Describe the relationship between environmental factors, microbiome composition, and celiac disease.

Answer 38

Changes in microbiome composition are associated with celiac disease. Environmental factors influencing the intestinal microbiota composition are thought to contribute to the development of CD.

Question 39

Do B cells play a crucial role in the amplification loop in celiac disease?

Answer 39

Yes, B cells play a crucial role in the amplification loop in celiac disease by efficiently internalizing and processing TG2-gluten complexes, leading to enhanced presentation of gluten peptides bound to HLA-DQ on TG2-specific B cells.

Question 40

Describe the role of microbial transglutaminase in helping patients with celiac disease.

Answer 40

Microbial transglutaminase can prevent binding to DQ2.5, reduce T cell activation, and modify gluten to prevent deamidation, thus reducing immunogenicity.

Question 41

Define how celiac disease is diagnosed using the ‘four out of five rule’.

Answer 41

Celiac disease is diagnosed based on typical signs and symptoms, antibody positivity, HLA-DQ2 and/or HLA-DQ8 positivity, intestinal damage, and clinical response to a gluten-free diet.

Question 42

How could transamidation by microbial transglutaminase prevent the deamidation of gluten in patients with celiac disease?

Answer 42

Transamidation can be used to prevent the deamidation of gluten, which enhances the binding of gluten epitopes to HLA-DQ molecules, thus reducing immunogenicity.

Question 43

Explain the Marsh score in the context of diagnosing celiac disease.

Answer 43

The Marsh score is used to assess intestinal damage in celiac disease, including villous atrophy and minor lesions, helping to classify different subtypes of the disease.

Question 44

How would you explain to your grandma why you cannot eat her gluten-packed apple pie if you had celiac disease?

Answer 44

I have celiac disease, and gluten in the apple pie can harm my intestines and make me sick. I need to avoid gluten to stay healthy.

Question 45

Describe the importance of carrying out mTG-mediated modification of gluten at higher pH values in patients with celiac disease.

Answer 45

Higher pH values help avoid the deamidation of gluten, which is known to increase immunogenicity, thus making the gluten safer for consumption by individuals with celiac disease.