GI Immunology Flashcards
Functional components of GALT? (1 afferent, 3 efferent)
Afferent - peyers patch (covered in M cells which interact with antigen and transport to T and B cells)
Efferent
1. Primed B lymphoblasts - migrate from peyers patch then return to gut to prduce IgA
2. Activated T cells
3. IEL - Intraepithelial lymphocytes activating CD8/4, TCR T cells and NK cells. E-cadherin on IEL binds HML-1 adhesion molecule of B7 integrin family to activate
Role of IgA? (3)
- Neutralises viruses, bacteria, toxins
- Prevents adherence of pathogens into gut epithelium
- Blocks antigen uptake into systemic immune system
What is gastritis type A and where and which cells does it affect?
Chronic inflammations of gastric mucosa associated with gland atrophy and loss of secretory cells. Affects fundus and body, not antrum and has high gastrin cells and serum but low IF and acid production and increases risk of gastric carcinoma
What is pernicious anaemia and what is it associated with? Presenting features?
Blood disorder with inability to utilize B12 associated with gastritis type A due to atrophy with IF deficiency and B12 malabsorption leading to megaloblastic anaemia.
Presenting features - tired, weakness, dyspnoea, sore tongue
Role of IF and 2 mechanisms of IF deficiency?
Glycoprotein produced by parietal cells bind to B12 so B12-IF carried to terminal ileum and absorbed after binding IF receptor so no IF means B12 malabsorption.
1. blocking antibodies compete for B12 binding site on IF
2. Binding antibodies with antigenic determinants on IF distinct from B12 binding site which will bind B12 to inhibit absorption
Coeliac disease: what is it and epidemiology?
Gluten sensitive enteropathy due to immunological hypersensitivity to gluten. High genetic risk, especially HLA-DQ2/8 in Europe
Coeliac disease: pathogenesis?
Exposure to gliadin and genetic suseptabilty cause reaction. Gliadin undergoes deamination by TTG in SI which is endocytosed and processed by APC and recognised by T cells. Activated T cells produce cytokines including IFN-G causing villous atrophy and crypt hyperplasia and an increase in IELs
Coeliac disease: clinical features?
diarrhoea, malabsorption which causes short stature, anaemia and peripheral neuropathy in children. leads to dermatitis, anaemia, osteoporosis, ataxia and infertility in adults. High risk of T cell lymphoma and is pre-malignant
Coeliac disease: diagnosis?
Jejunal biopsy whilst on gluten diet showing villous atrophy and serum IgA with serum IgA antibodies to TTG (but high false positive for IgA)
What is IPEX and APECED?
Deficiencies that may be related to autoimmune enteropathy causing severe and persistent diarrhoea (eg cows milk intolerance)
IPEX - mutation in FOX3 and depletion of T cells
APECED - mutation in AIRE which is TF and controls expression of self molecules in thymus relating to tolerance
Ulcerative Colitis: what, where, Th and genetics, smoking, cells involved?
musocal inflammation of mucosal layer typically starting from rectum and travelling backwards, Th2, 6-14% twins and 10x rish for 1st degree relative, smoking protective, neutro/eosinophils with more severe ulceration and loss of goblet cells
Crohns: what, where, Th and genetics, smoking, cells involved?
Transmural/glomerulomatous inflammation anywhere, particularly ileo-caecal region. Th1, 45% twins and 30x family risk, smoking harmful, lymphocytes, eosinophils
Pathogenesis of UC and CD?
Ulcerative colitis
- environmental factors trigger loss of tolerance to intestinal flora in genetically susceptible individuals. Smoking reduces risk while lack of breastfeeding and NSAIDS treatment increases risk. Mucosal layer is thinner throughout and reduced number of goblet cells
Crohns
- Intestinal inflammation due to abnormal immune reaction to intestinal flora leading to tissue damage. Linked to NOD2 mutations in genetically susceptible individuals. NOD2 variants lead to reduced responce to LPS in dendritic cells and imapired innate immune pathway, so others activated causing increase in neutrophils therefre inflammation
Managment of UC and CD?
UC - no treatment but infliximab (binds and inhibits TNF-a which is part of immune responce) may help
CD - Infliximab, antibodies to a4 integrins can block T cell migration, cytokine targetted with anti IL2/6 receptor inducing apoptosis, probiotics
What is calprotectin?
Calcium and zinc binding protien which indicates an excess of neutrophils in bowel indicating UC or CD
