The Mechanism of Celiac Disease

1. Gluten Enteropathy
Presentation by
Esfa khawar

2. Definition of Gluten Enteropathy
 Gluten enteropathy means disorder in small
intestine caused by the intake of Gluten
 Gluten is a protein found in wheat, barley, cereal,
pasta etc.
 In plant ,there is a defensive protein called
Prolamins »»
 Gluten is one of the type of Prolamins >> contain
toxic part Gliadin
 These toxic prolamins give the plant a protection
mechanism for their survival

3. Prolamins
 Dr. Alessio Fasano
 “All humans lack the enzymes required to break down
gluten.”
 The human gut is not equipped to break down prolamins
small enough to absorb any nutrients from them.
 This toxic affect is worse for people suffering from celiac
disease genetically.

4. Celiac Disease
 Gluten enteropathy >>also called >>Celiac
disorder
 Celiac disease is >>AUTOimmune disease
 Under normal conditions, the immune
system is designed to protect toxins,
bacteria, viruses, cancer cells, etc.

5. AUTOimmune disease
 In people with autoimmune disease,
 the immune system gets “confused” between antigen and
healthy body tissue
 it’s a tragic case of mistaken identity.
 “”The main difference between gluten intolerance and
celiac disease is the role of immune system towards
Gluten.””

6. Mechanism
 When a person intake gluten in diet (cereal, pasta ,wheat),
 enters into your stomach.
 Your stomach will reduce the size and structure of the food,
 turning it into chyme, and
 send it along to the small intestine to break it down further and
harvest the nutrients.
Intake food
Enters in
stomach
Chyme Small
intestine

7. Cont.
 In the case of gluten proteins (like gliadin), they need to
be broken down by the body before they’re useful, which
is difficult for us humans.
 Dr. Alessio Fasano
 “All humans lack the enzymes required to break down
gluten.”
 As these gliadin particles bounce around in the small
intestine, they start causing damage to the villi

8. Cont. INNATEimmune system/
inflammation
 undigested gliadin particles in the small
intestine causes a release of IL-8,(Inter
leukin) triggering the initial gut
inflammation
 IL8 activates INNATE immune system, first
layer of defense to react
 Their encounter start damaging small
intestine lining Enterocytes hence cause
GUT INFLAMATION at above gut wall.

9. LEAKY GUT
Zonulin/ tight junction
 Since INNATE immune system is not strong enough
for gliadin>>pass the barrier >> tricks ZONULINE
 (Zonulin is (Protein) a “gatekeeper” protein in the
human gut that controls the tight junctions of the
gut)
 >> cause zonulin level to rise >> Tight Junction in
return Opens Wide enough for large particle gluten
to enter inside Gut wall.
 Passing of Gluten through tight junction is called
LEAKY GUT.

10.  Now, gliadin is accumulating underneath the gut wall,
causing the enterocytes to release IL-15 (Inter leukin)
 ACTIVATES immune system Special Forces sending Intra
Epithelial Lymphocytes (IEL’s) with “inflammatory
mediators” such as TNF and IFN that
 contribute to more severe enterocyte damage
 causing inflammation
 The more severely those cells are damaged, the worse the
intestinal permeability gets
 and soon left with full-blown leaky gut syndrome.
 Now gliadin (and everything else), can freely pass through
the gut wall

11. Gliadin Cross link with Enzyme
Adaptive immune system
 Gliadin pass through gut wall >> enters underneath
the Gut Wall >> Crosslink with Enzyme Tissue
Transglutaminase (tTG)
 tTG= enzyme secreted to repair damaged Intestinal
cell Enterocytes
 >> on Crosslink of Gliadin/tTG >> ADAPTIVE immune
system enters ( special, powerful and strong
response ) contains Antibodies >> comes into
action>> recognize and destroys the antigens.

12. Cont.
 However
 Greater is the GUT Leak << Greater will be
Cross link <<
 Antibodies mistakenly start attacking
enterocyte cells ..
 this situation is called Autoimmune disease

13. 3 Inflammations
 Remember Immune system is already busy fighting Gliadin
above the Gut wall causing initial inflammation
 immune system fighting Gliadin is inside Gut Wall
causing inflammation
 Now Antibody’s mistaken attack on intestine cell
causing Inflammation.
 all three processes leading to the destruction of the
enterocyte cells lining the gut wall in their own special
way.
 Over time, these attack gets bad enough that they
completely destroy the microvilli of the intestinal lining.
 start infiltrating the body

14. Flattening
Damaged
completely

15. Summary of Mechanism
Gluten intolerance