Immunity, Inflammation, and Allergy in the gut

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Immunity, Inflammation, and Allergy in the gut

• By Thomas T. Macdonald and Giovanni Monteleone
• Presented By Alesha Purnell

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Outline

• Introduction
• The Gut Mucosal and Epithelial Barrier
• How the gut controls inflammation
• Crohns Disease
• Ulcerative Colitis
• Celiac Disease
• Conclusion

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Introduction

• There are two major forms of inflammatory bowel
  diseases which are crohns disease and ulcerative
  colitis.
• The cause of IBD is unknown, however it appears
  to involve
• the interaction of environmental factors
• host micro flora
• genetic predisposition
• abnormal immune response or auto immune response
  within the intestinal wall. (1)

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Introduction

• The immune system is usually able to defend the
  body against any potentially harmful organisms or
  substances in its surrounding environment.
• However, when individuals who have immune
  reactivity that becomes excessive, chronic
  inflammation begins and auto immune diseases
  occur.(2)

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The Gut and Epithelial Barrier
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The Gut Mucosal Barrier

• Gut mucosal barrier
• The mucosal immune system uses a number of
  mechanisms to protect the host against and
  aggressive immune response to luminal
  contents.(3)
• These include
• A strong physical barrier
• The presence of luminal enzymes that alter the
  nature of the antigen itself
• The presence of regulation in organized and
  disorganized lymphoid tissue of the gut.
• The production of antibody
• IgAwhich is secreted by exocrine glands and
  defends against bacterial cells and viruses. (3)

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The Gut Mucosal Barrier

• A major component of the mucosal barrier are the
  presence mucin genes.
• Mucin glycoproteins which lines the surface of
  epithelium from the nasal cavity to the rectum.
• Serve as a reservoir for IgA.(3)
• Goblet cells that produce mucus continuously
  produces a thick barrier that covers the adjacent
  epithelium.
• Particles, bacteria and viruses become trapped in
  the mucus layer and are removed by the
  peristaltic process of the gut. (3)

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Mucin
http//www.pathguy.com/histo/088.htm
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Goblet cell
http//science.nhmccd.edu/Biol/tissue/column.html
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The Gut Mucosal Barrier

• This barrier has the ability to prevent potential
  pathogens and antigens from gaining access to the
  underlying epithelium (non-immune exclusion).(3)

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Intestinal Epithelial Cells

• Intestinal epithelial Cells
• Antigens are able to cross the epithelial barrier
  by getting in between the tight junctions
  probably through the tips of the villus where
  they shed.
• They may also enter through the
  follicle-associated epithelial (FAE) surface
  which overlies organized lymphoid tissue of the
  intestinal wall. (2)
• The epithelium that is on top of the gut
  associated lymphoid tissue (GALT) contains M
  cells that are in charge of transporting gut
  bacteria and antigens from the lumen of the gut
  to the lymphoid tissue.(2)

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http//www.good2use.com/knet/bse/gut.htm
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Intestinal Epithelial Cells

• Intestinal epithelial cells (IECs) express a
  number of cell surface molecules (restriction
  element) involved in the T-cell responses.
• An antigen presenting cell has three major
  characteristics
• It expresses products of class 2 major
  histocompatibility complex (HLA-DR)
• Takes up antigens by either receptor mediated or
  fluid phase endocytosis.
• Antigens are processed within endosomes and
  loaded onto class 2 molecules where they are
  expressed on the cell surface, where it will be
  able to interact with specific t-cell
  receptors.(3)

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Intestinal Epithelial Cells

• Dentritic cells which are located within the
  lamina propria have the ability to reach through
  epithelial cells so that they can sample gut
  bacteria.(2)
• Intestinal epithelium is also filled with CD8 T
  cells .
• Glycoprotein that serves as a co-receptor which
  is expressed on the surface of cytotoxic
  T-cells.(2)

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Intestinal Epithelial Cells

• Lamina propria also contains CD4 T-cells which
  are
• Glycoprotein that are expressed on the surface of
  the T helper cells , regulatory cells and
  dendritic cells.
• They are also co receptors for the T-cell
  receptor (TCR).(4)

• Macrophages and IgA antibodies are present which
  are able produce plasma cells.
• The potential of damaged to tissue by the T cells
  responses should be stopped by the
  immunosuppressive cytokine and regulatory T
  cells.(2)

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(2)
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How inflammation is controlled in the gut
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How inflammation is controlled in the gut

• An increase in epithelial permeability plays a
  major part in the development of chronic gut T
  cell-mediated inflammation.
• CD4 t cells that are activated by gut antigens in
  the peyers patches migrate to the Lamina propria.
• Under normal condition these cells die by
  apoptosis.
• If there is an increase in epithelial
  permeability this will allow antigens to enter
  the lamina propria which triggers T cell
  activation.
• This decreases the tolerance mediated by
  immunosuppressive cytokines and may involve T
  regulatory cells.
• Pro-inflammatory cytokine further increase the
  epithelial permeability which starts the
  inflammation process.(1)

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(2)
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Preyers Patch
http//www.kumc.edu/instruction/medicine/anatomy/h
istoweb/lymphoid/lymph07.htm
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Crohns Disease
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Crohns Disease

• Crohns disease normally effects the small and
  large intestines in a segmental manner.
• The most common pattern of involvement
• 50-60 is combination of the distal ileum and
  the colon
• 15-25 of cases involves the small intestine or
  the colon.(1)

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Crohns Disease

• Caused by an over exagerated cell mediated immune
  response to antigens of the normal bacteria
  flora.
• Can affect any part of the gut from the mouth to
  the anus.
• Most commonly found in the ileum and the colon.
• Occurs in patches (areas of normal mucosa and
  ulcers are in between(2)

• Inflammation is mainly caused by T -cells and
  macrophages.
• Inflammatory cells are present throughout the gut
  wall.(2)

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Ulcerative Colitis
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Ulcerative Colitis

• 10-20/100,000 per year
• The cause is unknown
• UC occurs first in the rectum and as the disease
  begins to progress lesions begin to form
  proximally.
• Inflammation is continuous and is restricted to
  the colon.(2)

• Inflammation is restricted to the mucosa
• Neutrophils are the major cells that cause the
  inflammation
• They form got abscesses and cause damage to the
  epithelium.
• This causes mucus to not be secreted by goblet
  cells.(2)

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2
A normal colon (contains glands that are filled
with goblet cells that produce mucus small
lymphoid follicle with FAE on the left, B
Crohns disease (mucosal thickening is presented
and there is a distortion in glands there is
also a large amount of lymphoid infiltrate and
there is an ulcer that generates through the
mucosa from the lumen submucosa, C Ulcerative
colitis (the mucosa is thickened and is full of
inflammatory cells there are many neutrophil
filled chambered abscesses are present).
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Celaic Disease
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Celiac Disease

• Affects 0.5 and is most prevalent where wheat,
  barley and rye are major factor in the diet.(2)
• Known as gluten-sensitive enteropathy.
• Characterized by inflammation of the small
  intestinal mucosa that results from a immunologic
  intolerance to the ingestion of gluten.(5)

• Celiac disease differs from most IgE mediated
  food allergies because its inflammatory response
  is induced in the primary site of the damage
  (small intestinal mucosa).(5)
• IgE antibody subclass found only in mammals
• Capable of triggering most immune reactions.(6)

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Celiac Disease
Left normal intestinal villi right intestinal
villi affected by celiac disease
http//www.uihealthcare.com/news/currents/vol4issu
e2/celiacdiseae.html
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Conclusion
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Conclusion

• In the battle against infectious disease, the
  immune system cannot afford to proceed with
  caution.
• The failure to be effective and to respond to
  pathogen lethally will lead to the pathogens
  being able to infiltrate the body.
• It would probably be an unrealistic goal to try
  and prevent chronic inflammation in the gut,
  however, more attention has been paid on new
  treatments and a better understanding of the
  disease

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References

• Mahan, KL.s Esccott-Stump S. Food,Nutrition, and
  Dirt Therapy.(2004) 11th Edtion pgs 713-721.
• MacDonald T.T., Monteleone. Immunit,
  Inflammation, Allergy in the Gut. (2005).
  Science. Vol.307pgs 1920-1924.
• Mayer L., Mucosal Immunity. (2003). Pediatrics.
  Vol.111 pgs 1595-1600.
• Lammacone et al. Platelets Mediate Cytotoxic
  T-lymphocyte-damage. (2005). Nature Medicine.
  Vol.111 pgs 1167-1169
• Murray J. The widening Spectrum of Celiac
  disease.(1999). American Journal of Clinical
  Nutrition. Vol.69. pgs 354-357.
• Pooja T. et al. Allergen Drives Class Switching
  to IgE Nasal Mucosa Rhinitis.