Immunology of CELIAC DISEASE Ibrahim, Ibrahim; Kandoth, Littin; Naqvi, Shabab; Sims, Tyreen; Julien, Tabitha Mentor: Dr. Sanil Manavalan Columbia University, College of Physicians & Surgeons

Celiac disease a digestive disease that damages the small intestine and interferes with absorption of nutrients from food . When people with celiac disease eat foods containing gluten, their immune system responds by damaging the small intestine. Because the body's own immune system causes the damage, celiac disease is considered an autoimmune disorder.

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 Cytokine – proteins secreted by macrophages and leukocytes that stimulate or inhibit the proliferation or function of immune cells. Interleukin – cytokines that only affect leukocytes. Lymphocyte – A type of leukocyte (white blood cell) 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 and bad stuff Cytotoxic T-Cell – kills with cytotoxins B-Cell – creates antibodies. Antigen – invading microbe Antibody – protein that fights bacteria and viruses. Cytokines

The Gut Lumen Villi- (singular: villus) are tiny, finger-like structures that protrude from the wall of the intestine -Microvilli- hairlike structure on the surface of absorptive and secretory epithelial cells Epithelial Tissue- layer of cells which line the GI tract Enterocytes – layer between gut lumen and absorptive cells diagram

LAMINA PROPRIA AND INTRA EPITHILIAL SPACE GUT LUMEN GUT LUMEN Gliadin Inflammation & Damaged enteroctytes Enterocytes ab T cell receptor Helper T cell Lymphocytes (T cells , Natural Killer cells and B cells) Plasma cells Antibodies anti-gliadin anti-endomysial And tissue trasgliutaminase Cytokines (Interferon-g, TNF-a, IL-15 etc) HLA-DQ2/DQ8 molecule Antigen Presenting Cell LAMINA PROPRIA AND INTRA EPITHILIAL SPACE

Mucosal Immune System

Objective To find the cytokine levels in the serum of patients in the following groups 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 DEFINITION: technique for counting, examining and sorting microscopic particles suspended in a stream of fluid ROLE IN OUR EXPERIMENT:

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Harlem Children Society THANK YOU To: Dr. Sanil Manavalan Dr. Jamal Naiyer Sindhu Kunduvaram Dr. Sat Bhattacharya Harlem Children Society

Cytokines Cytokine Principal cell Targets and biological effects IL-1β IL-6 IL-8 IL-12 p70 IFN-γ TNF-α Principal cell Targets and biological effects Endothelial cells: activation B cells: proliferation of antibody producing cells Activator of neutrophils NK cells and T cells: IFN-gamma synthesis, increased cytolytic activity Macrophages: Activation Endothelial cells: Activation