Flashcards in FunMed: PBL 6 (Coeliac) Deck (32):
Which cells of the immune system recognise gluten and cause coeliac disease?
CD4 (Helper) T cells
What are the histological features of intestinal mucosa in coeliac disease?
Crypt hyperplasia, villous atrophy and increased infiltration of lymphoid cells
Which antibodies are tested for in the blood to diagnose coeliac disease?
anti-endomysium IgA, anti-tissue transglutaminase (tTG) IgA and IgG and antibodies to gliadin
Name the major types of MHC/HLA class I molecules
HLA A,B and C
Name the major types of MHC/HLA class II molecules
HLA DQ, DR, DP
What type of HLA molecule do 95% of people with coeliac disease have?
What maximises the likelihood that MHC molecules can bind to any particular peptide to present to T cells?
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)
What are the components of the innate immune system?
Physical and chemical barriers, phagocytes, dendritic cells, natural killer cells, complement
Outline the innate immune system
Immediate response, no memory, acts to destroy and contain until adaptive immune system ca take care of situation
What are the components of the adaptive immune system?
Humoral immunity (B cells) and cell-mediated immunity (T cells)
Outline the adaptive immune system
Slower response (1-2 weeks) and has memory
What is humoral immunity?
Immunity mediated by antibodies produced by B lymphocytes
What is cell-mediated immunity?
Immunity mediated by T lymphocytes (CD4 and CD8, helper and killer respectively)
What is the most common antibody?
Where is IgA antibody found and what does it do?
Mucosal areas, saliva, tears and breastmilk; prevents colonisation by pathogens
Where is IgD antibody found and what does it do?
Mainly antigen receptor on B cells which haven't been exposed to antigens --> activates basophils and mast cells to produce antimicrobial factors
Where is IgE antibody found and what does it do?
Binds to allergens and triggers histamine release from mast cells and basophils (asthma and allergies)
Where is IgG antibody found and what does it do?
Provides most of antibody-based immunity and can cross placenta to foetus
Where is IgM antibody found and what does it do?
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
How can coeliac disease be diagnosed from GI endoscopy?
Intestine has atrophic mucosa and flattened folds (no scalloping on surface)
How may genetics predispose someone to coeliac disease?
Presence of HLA DQ2 or DQ8 molecules (bind to gliadin more strongly)
Describe the structure of gluten
Gliadin (chain) and glutenin (ropes) bind to each other; gliadin is water-soluble, glutenin is insoluble
What foods is gluten present in?
wheat, oat, barley and rye
What is coeliac disease?
Disorder of small intestine which is characterised by malabsorption, villous atrophy and gluten intolerance
What are the symptoms of coeliac disease?
If eat foods with gluten: diarrhoea, bloating, flatulence, abdominal pain, weight loss, fatigue (malnutrition)
How is coeliac disease treated?
Prescription of gluten-free diet
Describe the role of Th1 cells (CD4)
Produce cytokines to activate macrophages using interferon gamma
Describe the role of Th2 cells (CD4)
Produce cytokines to activate B cells to produce antibodies using IL-4
Describe the pathophysiology of coeliac disease
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
What role does IgA usually play in coeliac disease?
Gliadin binds to SIgA which bind to transferrin receptor on enterocyte and pass out the other side
What role does IgA usually play in normal individuals against gliadin?
Normally secretory IgA binds to gladin to trap it in mucus which is then removed by peristalsis