Immunology of CELIAC DISEASE

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Immunology of CELIAC DISEASE

• Ibrahim, Ibrahim
• Mentor Dr. Sanil Manavalan
• Columbia University, College of Physicians and
  Surgeons

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• Celiac disease
• a digestive disease that damages the small
  intestine and interferes with absorption of
  nutrients from food
• it is a genetic disorder
• some of the symptoms of celiac disease are
  diarrhea, weight loss, malnutrition, etc
• when people with celiac disease eat foods
  containing gluten, their immune system responds
  by damaging the small intestine
• Diagnosis is by intestinal biopsy histological
  grading and presence of serum auto- antibodies.
• because the body's own immune system causes the
  damage, celiac disease is considered an
  autoimmune disorder

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• 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
• Crohns Disease- affects the gut
• Multiple Sclerosis- affects the brain

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Key Terms

• Cytokines 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 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.

Lymphocytes
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The Gut Lumen

• Villi- (singular villus) are tiny, finger-like
  structures that protrude from the wall of the
  intestine
• -Microvilli- hair-like structure on the surface
  of absorptive and secretory epithelial cells
• Epithelial cells - layer of cells which line the
  GI tract

Diagram
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GUT LUMEN
GUT LUMEN
Glaidin
Enterocytes
LAMINA PROPRIA AND INTRA EPITHILIAL SPACE
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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-1ß
• IL-6
• IL-8
• IL-12 p70
• IFN-?
• TNF-a

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Methods

• Dilution of StandardsStandards were used to
  calibrate the flow cytometer. The Standards were
  diluted by 11, 12, 14, 18, 116, 132, 164,
  1125, 1250, and 1500. The standards were just
  FACS buffer solutions in water.
• Calibration of CytometerTo do this, we had
  solutions of the cytokines we were testing. After
  this we calibrated the equipment so it recognizes
  which wavelengths of light are representative of
  specific cytokines.
• Excel SpreadsheetTo analyze the results, and
  present them to the scientific community, we used
  Excel spreadsheet to put the data into a
  comprehensible graph format.

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Flow Cytometry
DEFINITION technique for counting, examining and
sorting microscopic particles (such as cells)
suspended in a stream of fluid ROLE IN OUR
EXPERIMENT To analyze concentrations of
cytokines in the sera of patients using capture
beads which detect the cytokines.
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Hypothesis

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

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Results
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Results Cont.
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Conclusions
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
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Acknowledgements

• Dr. Sanil Manavalan - Mentor
• Dr. Jamal Naiyer Co-mentor
• Sindhu Kunduvaram Undergraduate Student
• Dr. Sat Bhattacharya Coordinator OF HCS
• Mrs. Susan Farenholtz Coordinator of Project
  Seed
• Harlem Children Society
• Project Seed

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Cytokines
Cytokine IL-1ß IL-6 IL-8 IL-12 p70 IFN-? TNF-a 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