Immunological Basis of Gastrointestinal Disorders

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Immunological Basis of Gastrointestinal
Disorders
Maha A. El Bassuoni Ass.Prof. of Clinical
Pathology Faculty of Medicine , Menoufiya
University, EGYPT
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The immune System

• The cells and molecules responsible for immunity
  constitute the immune system.
• The immune system has to be able to respond to
  protect the human body from a very large number
  of foreign antigens introduced at any site.

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Mucosal Immune System

• The mucosal immune system is recognized by
  differences from its systemic counterpart.
• It is recognized that the mucosal immune
  response is also distinct, largely focused on
  suppressing immunity rather than promoting it.

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Gut Associated Lymphoid Tissue(GALT)
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Structure of Secretory IgA

• It consists of at least two IgA molecules
  covalently linked by a J chain and the secretory
  component, which is added as the antibody crossed
  the mucosal epithelial cells into the lumen.

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Gastrointestinal Organs Disorders

• Gastrointestinal Disorders
• Pancreatic Disorders
• Hepatobiliary Disorders
• Orodental Disorders

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A. Gastrointestinal Disorders1. Food -Induced
Gastrointestinal DisordersI. Gluten-sensitive
Enteropathy Celiac Disease
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A. Gastrointestinal Disorders1. Food -Induced
Gastrointestinal DisordersI. Gluten-sensitive
Enteropathy Celiac Disease

• Laboratory Investigation
• Hypoalbuminemia hypoproteinemia
• Iron, folate, and, vB12 deficiency.
• PT prolonged
• circulating IgA and IgG to gliadin
• IgA antibody to endomysium has higher sensitivity
  and specificity

• Endomysial antibodies on smooth muscle

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A. Gastrointestinal Disorders1. Food -Induced
Gastrointestinal Disorders II. Gastrointestinal
food allergy diseases

• Allergy is an immunological phenomena
• refers to certain diseases in which immune
  responses to environmental antigens causes tissue
  inflammation and organ dysfunction.
• Hypersensitivity and Sensitivity used as synonyms
  for allergy.

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A. Gastrointestinal Disorders1. Food -Induced
Gastrointestinal Disorders II. Gastrointestinal
food allergy diseases

• a. Dietary Protein-Induced Proctitis/Proctocolitis
  
• eosinophilic infiltration and occasionally
  lymph-nodular hyperplasia.
• b. Dietary Protein Enteropathy
• T cell responses
• c. Dietary Protein Enterocolitis milk-specific T
  cell response
• d. Immediate Gastrointestinal Hypersensitivity
• mediated by IgE antibody
• e. Eosinophilic Gastroenteropathies
• both cell-mediated and IgE antibody-mediated

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d. Immediate Gastrointestinal Hypersensitivity
II. Gastrointestinal food allergy diseases

• Allergy testing
• In vitro tests
• Tests for IgE Abs (RAST).
• Tests for IgG Abs .
• Tests for Immune complex.
• Tests for Lymphocyte stimulation

• Antigen cross links IgE on mast cells in tissues
  Mast Cell Degranulation

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A. Gastrointestinal Disorders2. Chronic Atrophic
Gastritis

• Normal Atrophic

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A. Gastrointestinal Disordes 2. Chronic Atrophic
Gastritis Autoimmune Atrophic Gastritis
(Type A)
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A. Gastrointestinal Disordes 2. Chronic Atrophic
Gastritis Autoimmune Atrophic Gastritis
Types of intrinsic factor antibodies
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A. Gastrointestinal Disordes 2. Chronic
Atrophic Gastritis Autoimmune Atrophic
Gastritis

• Anti-Parietal Cells (Rat stomach)

• Diagnosis of autoimmune gastritis however, it can
  be ascertained histologically
• (1) Antiparietal and anti-IF antibodies in the
  serum.
• (2) Achlorhydria and hypergastrinemia
• (3) serum v. B12 levels, usually low.

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A. Gastrointestinal Disordes 2. Chronic
Atrophic Gastritis Gastric autoantibodies
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A. Gastrointestinal Disorders 3.Human
immunodeficiency Virus Enteropathy

• HIV infection
• HIV is one of the group of viruses known as
  retroviruses.
• When HIV infects a human cell, its RNA has to be
  converted to DNA.
• It exerts its effect both directly, through
  infection of the intestinal cells and indirectly
  through impairment of the intestinal immune
  response.
• The antigenicity of various components provides a
  means for detection of antibody, and the basis
  for most HIV testing.

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HIV Virus Lifecycle
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Gastrointestinal Disorders 4.Whipple's Disease

• Diagnosis
• microscopic examination of specimens. The
  established cultivation of the bacterium and the
  isolation from infected intestinal biopsies
• PCR analysis, which has high sensitivity and
  specificity.

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A. Gastrointestinal Disorders 5. Inflammatory
Bowel Diseases I. Crohn's Disease
II. Ulcerative colitis
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A. Gastrointestinal Disorders 5. Inflammatory
Bowel Diseases

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A. Gastrointestinal Disorders 5. Inflammatory
Bowel Diseases I. Crohn's Disease
II. Ulcerative colitis
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A. Gastrointestinal Disorders 5. Inflammatory
Bowel Diseases I. Crohn's Disease
II. Ulcerative colitis

• Based on the cytotoxicity findings Sauberman et
  al. postulate that in mice the stimulation of NKT
  cells through antigen presented to these cells by
  CD1d-bearing DCs or epithelial cells (MHC
  class1-like).
• The stimulated NKT cells, then begin to produce
  IL-13, they become capable of lysing epithelial
  cells, leads to epithelial cell loss and
  ulceration.

• Enteric bacterial flora has been reported in both
  animal models and IBD patients.
• In animal models Oslon et al have reported that
  CD4CD45RBloCD25 regulatory T cells (Treg cells)
  prevent colitis induced by transferring effector
  CD4CD45RBhiCD25 T cells into SCID mice through
  mechanisms involving TGF-ß and IL-10.

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B. Pancreatic Disorders

• Laboratory tests
• ? serum amylase and lipase only during acute
  attacks of pancreatitis, usually early in the
  course of the disease.
• ? concentrations of serum trypsin are relatively
  specific for advanced chronic pancreatitis. (not
  sensitive enough)
• ANA test
• Fecal tests (Steatorrhea a manifestation of
  advanced disease)
• Pancreatic function tests

• Autoimmune pancreatitis is uncommon and accounts
  for less than 1 of cases of chronic
  pancreatitis.
• local expression and release of TGF-ß, enhances
  synthesis of extracellular matrix proteins,
  (collagens, fibronectin).
• MCP-1mRNA IL8 and ENA mRNA in centroacinar
  ducts.

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C. HEPATOBILIARY DISORDERS

• 1. LIVER DISORDERS
• Viral Hepatitis
• Autoimmune Hepatitis
• 2. BILIARY DISORDERS
• Primary Biliary Cirrhosis (PBC)
• Primary Sclerosing Cholangitis (PSC)

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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS I.
Viral Hepatitis HAV HEV
Acute HEV infection Pregnant female in 3rd
trimester 25 risk of mortality
Epidemics by contaminated water or food suorce
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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS
I. Viral Hepatitis HBV HDV
Progress to cirrhosis
Flare of HBV and FHF
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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS
I. Viral Hepatitis HCV
85 chronic cases Associated with autoimmune
hepatitis
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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS
II. Autoimmune Hepatitis
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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS
II. Autoimmune Hepatitis
Laboratory diagnosis
Anti SLA

• Autoantibodies Autoimmune hepatitis type 1 is
  characterized by positive ASMA and ANA.
• Type 2 marked by a positive antiLKM-1 antibody.
• Type 3 is marked by a positive anti-SLA antibody.

• Anti-actin

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C. HEPATOBILIARY DISORDERS1. LIVER DISORDERS
II. Autoimmune Hepatitis

• Laboratory Diagnosis
• Hypergammaglobulinemia
• ?AST and ALT
• ?S. bilirubin and ALP
• Hypoalbuminemia and prolongation of PT
• Other common laboratory abnormalities
• mild leucopenia
• Normochromic anemia
• Coombs-positive hemolytic anemia
• Thrombocytopenia

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C. HEPATOBILIARY DISORDERS2. BILIARY DISORDERS
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C. HEPATOBILIARY DISORDERS2. BILIARY DISORDERS
I. Primary Biliary Cirrhosis
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C. HEPATOBILIARY DISORDERS2. BILIARY DISORDERS
I. Primary Biliary Cirrhosis

• The hallmark of the disease is the presence of
  AMAs in the sera.
• AMAs found in 90-95 of patients and have a
  specificity of 98.

• Elevation of
• ALT
• AST
• ALP
• GGTP.
• Lipid levels (HDL) and cholesterol levels may be
  increased .
• Elevated bilirubin level
• Prolonged PT
• Decreased albumin level

AMA
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C. HEPATOBILIARY DISORDERS2. BILIARY DISORDERS
II. Primary Sclerosing Cholangitis
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C. HEPATOBILIARY DISORDERS2. BILIARY DISORDERS
II. Primary Sclerosing Cholangitis

• Laboratory Diagnosis
• Increased ALP and total bilirubin,
• Increased transaminases
• Hypergammaglobulinemia,
• P-ANCA (65-85 of cases)
• ANA, (ASMA), anti-cardiolipin autoantibodies
• Anti-mitochondrial autoantibodies (AMA) are
  negative

• P-ANCA

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D. ORODENTAL DISORDERS

• 1. Inflammatory Periodontal Diseases
• Gingivitis and periodentitis
• polymorph induced damage, complement induced
  damage (through IgG (IgG2). peripheral T cell
  reactivity to plaque antigens
• Juvenile Periodontitis defects in granulocyte or
  monocyte function conventional.

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D. ORODENTAL DISORDERS

• 2. Recurrent Aphthous Ulceration
• Raised level of circulating antibody to saline
  extract of fetal oral mucous membrane.
• These antibodies may be a response to exposed
  tissue antigen that previously been protected
  from immune system. (Ag against oral mucous
  membrane, epithelial cells. or viral Ags).
• CMI proved by an infiltrate of lymphocyte

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D. ORODENTAL DISORDERS

• 3.Oral Candidiasis
• A threshold number of systemic CD4 cells to
  protect the oral mucosa together with the status
  of local immunity.
• HIV infected persons with and without OPC had a
  Th2-type salivary cytokine profile suggestive of
  susceptibility to Candida infection
• GM-CSF are important in the generation of
  effective immunity to C. albicans. .
• 4. Oral Hairy Leukoplakia
• There is correlation of diminished CD4 T
  lymphocyte count to the occurrence of the
  lesions.

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Thank You