Immunology of CELIAC DISEASE

1. Immunology of CELIAC DISEASE Nertila Ujkaj Mentor: Dr. Sanil Manavalan Columbia University, College of Physicians and Surgeons

2. What is Celiac Disease? a 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

3. The Gut Lumen • Villi- finger-like structures that protrude from the wall of the intestine -Microvilli- hairlike structure on the surface of absorptive and secretoryepithelial cells • Epithelial cells- layer of cells which line the GI tract

4. 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

5. 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

6. 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.

7. Cytokine

8. 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 Aim

9. 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)

10. Hypothesis • Increased serum levels of inflammatory cytokines in patients with active and refractory celiac disease • Normal levels of cytokines in gluten –free diet

12. Our Results

13. …continued

14. 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

15. 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. 2April 04. www.gihealth.com/ newsletter/previous/029.html • “Cope with cytokine.” July 03. “Cope.” <http://www.copewithcytokines.de/>

16. Acknowledgements • Dr. Sanil Manavalan • Dr. Jamal Naiyer • Sindhu Kunduvaram • Dr. Sat Bhattacharya • Harlem Children Society • Shabab • Ibrahim

17. THANK YOU THE END!