Immunology of CELIAC Immunology of CELIAC DISEASEDISEASE

Ibrahim, Ibrahim; Kandoth, Littin; Ibrahim, Ibrahim; Kandoth, Littin; Naqvi, Shabab; Sims, Tyreen; Naqvi, Shabab; Sims, Tyreen;

Julien, TabithaJulien, TabithaMentor: Dr. Sanil ManavalanMentor: Dr. Sanil Manavalan

Columbia University, College of Physicians & Columbia University, College of Physicians & SurgeonsSurgeons

Celiac disease Celiac disease

•a digestive disease that damages the small a digestive disease that damages the small intestine and interferes with absorption of intestine and interferes with absorption of nutrients from food .nutrients from food .

•When people with celiac disease eat foods When people with celiac disease eat foods containing gluten, their immune system responds containing gluten, their immune system responds by damaging the small intestine.by damaging the small intestine.

•Because the body's own immune system causes Because the body's own immune system causes the damage, celiac disease is considered an the damage, celiac disease is considered an autoimmune disorder.autoimmune disorder.

AUTOIMMUNE DISEASE: condition in AUTOIMMUNE DISEASE: condition in which the immune system mistakenly which the immune system mistakenly attacks the body's own organs and attacks the body's own organs and tissuestissues

• Type 1 Diabetes – affects the pancreasType 1 Diabetes – affects the pancreas• Systemic Lupus erythmatotosus Systemic Lupus erythmatotosus

(Lupus)– affects the skin(Lupus)– affects the skin• Crohn’s Disease- affects the gutCrohn’s Disease- affects the gut• Multiple Sclerosis- affects the brainMultiple 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 LumenThe Gut Lumen• Villi- Villi- (singular: villus) are tiny, finger-(singular: villus) are tiny, finger-

like structures that protrude from the like structures that protrude from the wall of the intestinewall of the intestine-Microvilli- -Microvilli- hairlike structure on the hairlike structure on the surface of absorptive and secretorysurface of absorptive and secretory epithelial cells epithelial cells

• Epithelial Tissue- Epithelial Tissue- layer of cells which layer of cells which line the GI tract line the GI tract

• Enterocytes – Enterocytes – layer between gut layer between gut lumen and absorptive cellslumen and absorptive cells diagram

Gliadin

Enterocytes

GUT LUMEN

Antibodiesanti-gliadin

anti-endomysialAnd tissue trasgliutaminase

Cytokines(Interferon-, TNF-IL-15 etc)

Lymphocytes(T cells , Natural Killer cells and B cells)

Plasma cells

T cell receptor

Helper T cell

HLA-DQ2/DQ8molecule

Antigen Presenting Cell

GUT LUMEN

LAMINA PROPRIA AND INTRA EPITHILIAL SPACE

Inflammation &Damaged

enteroctytes

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:

Results

Conclusions

References

THANK YOU

To: Dr. Sanil ManavalanDr. Jamal Naiyer

Sindhu KunduvaramDr. Sat Bhattacharya

Harlem Children Society

Cytokines

Cytokine IL-1β

IL-6

IL-8IL-12 p70

IFN-γTNF-α

Principal cell Targets and biological effectsEndothelial cells: activation B cells: proliferation of antibody producing cellsActivator of neutrophils NK cells and T cells: IFN-gamma synthesis, increased cytolytic activityMacrophages: ActivationEndothelial cells: Activation