Introduction to Immunology of Celiac Disease

Immunology of CELIAC DISEASE Nertila Ujkaj Mentor: Dr. Sanil Manavalan Columbia University, College of Physicians and Surgeons What is Celiac Disease? digestive disease damaging the small intestine interfering with absorption of nutrients from food genetic disorder Symptoms -diarrhea -weight loss -malnutrition -anemia When a CD patient eats food containing gluten, the immune system responds by damaging the small intestine 1 out of every 250 people may have CD; only 1 out of 10 people may be actually diagnosed and are aware of their condition because the body's own immune system causes the damage, celiac disease is considered an autoimmune disorder a The Gut Lumen Villi- finger-like structures that protrude from the wall of the intestine -Microvilli- hairlike structure on the surface of absorptive and secretory epithelial cells  Epithelial cells- layer of cells which line the GI tract  Celiac Sprue Under the Microscope •cross-section of healthy villi increase the net surface area of the small intestine •normal finger-like villi eroded away. •surface is flattened •"autoimmune" reaction AUTOIMMUNE DISEASE: condition in which the immune system mistakenly attacks the body's own organs and tissues -Type 1 Diabetes – affects the pancreas -Systemic Lupus erythmatotosus (Lupus)– affects the skin -Crohn’s Disease- affects the gut -Multiple Sclerosis- affects the brain Key Terms •Cytokines – proteins secreted by macrophages and leukocytes that stimulate or inhibit the proliferation or function of immune cells. –Interleukin – cytokines affecting leukocytes. •Lymphocyte – A type of leukocyte of the immune system. –T-Regulatory Cell – slows down and stops immune response –T-Helper Cell – has antigen-receptors, releases cytokines –Natural Killer Cell – kills macrophage –Cytotoxic T-Cell – kills cells that produce foreign antigens such as cells infected by viruses –B-Cell – creates antibodies. •Antigen – invading microbe •Antibody – protein that fights bacteria and viruses. Cytokine cytokine Function and effect IL-1β IL-6 IL-8 IL-12 p70 IFN-γ TNF-α mediates acute inflammatory responses stimulates the proliferation of B-lymphocytes; and increases neutrophil production. Activator of neutrophils a primary mediator of early innate immune responses to intracellular microbes; inducer of cell-mediated immunity Activates macrophages Activates endothelial cells Aim  To find the cytokine levels in the serum of patients in: – Healthy Patients (Control) – Active Celiac Disease Patients – Celiac Disease patients on  Gluten-free diets – Refractory Disease Patients The following cytokines were checked in the serum of these patients; – IL-1β – IL-6 – IL-8 – IL-12 p70 – IFN-γ – TNF-α Flow Cytometry  A method of measuring the number of cells, the percentage of live cells, and certain characteristics of cells, such as size & shape in a sample ROLE IN OUR EXPERIMENT: To analyze concentrations of cytokines in the sera of patients using capture beads which detect the cytokines. (by Shabab) Hypothesis Increased serum levels of inflammatory cytokines in patients with active and refractory celiac disease Normal levels of cytokines in gluten –free diet Our Results Cytokine Concentrations 120.0 100.0 80.0 pg/mL 60.0 Controls (n=9) Gluten-Free Diet (n=20) Active Celiac Disease (n=14) Refractory Disease (n=11) 40.0 20.0 0.0 IFN-γ TH1/TH2 IL-1β IK IL-2 IL-4 TH1/TH2 TH1/TH2 IL-6 IK Cytokines IL-8 IK IL-10 IK IL-12 p70 TNF-α IK IK …continued Cytokine Concentrations 160.0 140.0 120.0 IFN-γ TH1/TH2 IL-1β IK 100.0 IL-2 TH1/TH2 IL-4 TH1/TH2 IL-6 IK IL-8 IK IL-10 IK 60.0 IL-12 p70 IK TNF-α IK pg/mL 80.0 40.0 20.0 0.0 Controls (n=9) Gluten-Free Diet (n=20) Active Celiac Disease (n=14) Refractory Disease (n=11) Patients Conclusion • Pro-inflammatory cytokines such as Interferon –gamma and IL-8 seemed to be increased in both patients with active disease and Celiac patients on a gluten-free diet. • We are analyzing the data on an individual patient by patient basis to determine if there is a correlation with the biopsy grade for each patient References  Abul K Abbas, MBBS: Andrew H Litchman, MD, PHD. Cellular and Molecular Immunology. Pgs- 1- 104. Fifth edition “Intestinal Villi” No date. Online image. Anaglyph stereo images. www.udel.edu/.../ anaglyphpage/anaglyph.html “Noraml Villi/Loss of Villi.” No date. Online image. Celiac Sprue - When Bread Is Poison. 2 April 04. www.gihealth.com/ newsletter/previous/029.html “Cope with cytokine.” July 03. “Cope.”    Acknowledgements Dr. Sanil Manavalan  Dr. Jamal Naiyer  Sindhu Kunduvaram  Dr. Sat Bhattacharya  Harlem Children Society  Shabab  Ibrahim  THANK YOU THE END!