FunMed: PBL 6 (Coeliac)

Question 1

Which cells of the immune system recognise gluten and cause coeliac disease?

Answer 1

CD4 (Helper) T cells

Question 2

What are the histological features of intestinal mucosa in coeliac disease?

Answer 2

Crypt hyperplasia, villous atrophy and increased infiltration of lymphoid cells

Question 3

Which antibodies are tested for in the blood to diagnose coeliac disease?

Answer 3

anti-endomysium IgA, anti-tissue transglutaminase (tTG) IgA and IgG and antibodies to gliadin

Question 4

Name the major types of MHC/HLA class I molecules

Answer 4

HLA A,B and C

Question 5

Name the major types of MHC/HLA class II molecules

Answer 5

HLA DQ, DR, DP

Question 6

What type of HLA molecule do 95% of people with coeliac disease have?

Answer 6

HLA DQ2

Question 7

What maximises the likelihood that MHC molecules can bind to any particular peptide to present to T cells?

Answer 7

MHC molecules are polygenic (more than one type of class I and II) and polymorphic (multiple alleles in population so most individuals are heterozygous - two types)

Question 8

What are the components of the innate immune system?

Answer 8

Physical and chemical barriers, phagocytes, dendritic cells, natural killer cells, complement

Question 9

Outline the innate immune system

Answer 9

Immediate response, no memory, acts to destroy and contain until adaptive immune system ca take care of situation

Question 10

What are the components of the adaptive immune system?

Answer 10

Humoral immunity (B cells) and cell-mediated immunity (T cells)

Question 11

Outline the adaptive immune system

Answer 11

Slower response (1-2 weeks) and has memory

Question 12

What is humoral immunity?

Answer 12

Immunity mediated by antibodies produced by B lymphocytes

Question 13

What is cell-mediated immunity?

Answer 13

Immunity mediated by T lymphocytes (CD4 and CD8, helper and killer respectively)

Question 14

What is the most common antibody?

Answer 14

IgG

Question 15

Where is IgA antibody found and what does it do?

Answer 15

Mucosal areas, saliva, tears and breastmilk; prevents colonisation by pathogens

Question 16

Where is IgD antibody found and what does it do?

Answer 16

Mainly antigen receptor on B cells which haven’t been exposed to antigens –> activates basophils and mast cells to produce antimicrobial factors

Question 17

Where is IgE antibody found and what does it do?

Answer 17

Binds to allergens and triggers histamine release from mast cells and basophils (asthma and allergies)

Question 18

Where is IgG antibody found and what does it do?

Answer 18

Provides most of antibody-based immunity and can cross placenta to foetus

Question 19

Where is IgM antibody found and what does it do?

Answer 19

On surface of B cells as monomer, and in secretions as pentamer; eliminates pathogens in early stages of humoral immunity before there is enough IgG

Question 20

How can coeliac disease be diagnosed from GI endoscopy?

Answer 20

Intestine has atrophic mucosa and flattened folds (no scalloping on surface)

Question 21

How may genetics predispose someone to coeliac disease?

Answer 21

Presence of HLA DQ2 or DQ8 molecules (bind to gliadin more strongly)

Question 22

Describe the structure of gluten

Answer 22

Gliadin (chain) and glutenin (ropes) bind to each other; gliadin is water-soluble, glutenin is insoluble

Question 23

What foods is gluten present in?

Answer 23

wheat, oat, barley and rye

Question 24

What is coeliac disease?

Answer 24

Disorder of small intestine which is characterised by malabsorption, villous atrophy and gluten intolerance

Question 25

What are the symptoms of coeliac disease?

Answer 25

If eat foods with gluten: diarrhoea, bloating, flatulence, abdominal pain, weight loss, fatigue (malnutrition)

Question 26

How is coeliac disease treated?

Answer 26

Prescription of gluten-free diet

Question 27

Describe the role of Th1 cells (CD4)

Answer 27

Produce cytokines to activate macrophages using interferon gamma

Question 28

Describe the role of Th2 cells (CD4)

Answer 28

Produce cytokines to activate B cells to produce antibodies using IL-4

Question 29

Describe the pathophysiology of coeliac disease

Answer 29

Gliadin resists digestion --> interacts with CXCR3 receptor on enterocytes --> sends signal into cell to produce zonulin protein --> degrades tight junctions to allow passage into cell --> tTG deaminates gliadin --> tTG-gliadin complex --> binds to dendritic cell --> presented on HLA DQ2/8 --> T cells bind --> CD8 cells, attack anything like gliadin near surface --> CD4 cells --> B cells --> antibodies and memory cells

Question 30

What role does IgA usually play in coeliac disease?

Answer 30

Gliadin binds to SIgA which bind to transferrin receptor on enterocyte and pass out the other side

Question 31

What role does IgA usually play in normal individuals against gliadin?

Answer 31

Normally secretory IgA binds to gladin to trap it in mucus which is then removed by peristalsis

Question 32

Which molecules produced by T cells cause damage to villi?

Answer 32

interferon gamma (TH1 cells) and interleukin 4 (TH2 cells)