Transcript 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?
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
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
mediates acute inflammatory responses
IL-6
stimulates the proliferation of B-lymphocytes; and
increases neutrophil production.
IL-8
Activator of neutrophils
IL-12 p70
a primary mediator of early innate immune
responses to intracellular microbes; inducer of
cell-mediated immunity
IFN-γ
Activates macrophages
TNF-α
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
pg/mL
IL-4 TH1/TH2
IL-6 IK
80.0
IL-8 IK
IL-10 IK
IL-12 p70 IK
60.0
TNF-α IK
40.0
20.0
0.0
Controls (n=9)
Gluten-Free Diet (n=20)
Active Celiac Disease (n=14)
Patients
Refractory Disease (n=11)
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.”
<http://www.copewithcytokines.de/>
Acknowledgements
Dr. Sanil Manavalan
 Dr. Jamal Naiyer
 Sindhu Kunduvaram
 Dr. Sat Bhattacharya
 Harlem Children Society
 Shabab
 Ibrahim

THANK YOU
THE END!