Immune Tolerance and the Microbiome Overview

Questions and Answers

What role do short-chain fatty acids (SCFAs) play in immune tolerance?

They degrade gluten products in the intestine.

They influence dendritic cells and induce regulatory T-cells. (correct)

They stimulate the production of IL-15.

They inhibit dendritic cell function.

Which of the following is a consequence of gliadin binding to the chemokine receptor CXCR3?

Production of zonulin, leading to tight junction disassembly. (correct)

Stimulation of IgA production.

Activation of regulatory T-cells.

Enhanced MALT development.

How do Firmicutes enhance immune responses in the intestine?

By inhibiting the growth of beneficial bacteria.

By degrading gluten into non-reactive fragments.

Through TLR signaling and enhancing IgA production. (correct)

By reducing the production of IL-17.

What happens to intra-epithelial lymphocytes when IL-15 is produced by enterocytes in response to gliadin?

They express NK cell activating receptors. Signup and view all the answers

What characterizes the response of the small intestine to gluten in individuals with celiac disease?

Disruption of tight junctions allowing leakage of gliadin. Signup and view all the answers

What primary function does the lower esophageal sphincter serve?

Prevents reflux of gastric contents Signup and view all the answers

What initiates the vasovagal reflex known as receptive relaxation?

Swallowing and esophageal distension Signup and view all the answers

What occurs during gastric accommodation?

Stomach walls bulge to store food Signup and view all the answers

How much can a completely relaxed stomach typically hold?

0.8-1.5L Signup and view all the answers

What happens to the tone of the muscular wall of the stomach when food is present?

It gradually decreases Signup and view all the answers

What is the primary function of the stomach in the gastrointestinal tract?

Serves as a reservoir for food before it enters the small intestine Signup and view all the answers

Which of the following is NOT a main region of the stomach?

Duodenum Signup and view all the answers

What are the two main curvatures of the stomach called?

Lesser and greater Signup and view all the answers

What is the role of the lower esophageal sphincter?

Prevents gastric contents from refluxing into the esophagus Signup and view all the answers

Which part of the stomach is primarily involved in mixing food with gastric juices?

Body Signup and view all the answers

What term describes the mixture of saliva, food, and gastric juice in the stomach?

Chyme Signup and view all the answers

How many main regions are identified in the stomach anatomy?

4 Signup and view all the answers

Which sphincter is located at the exit of the stomach leading to the small intestine?

Pyloric sphincter Signup and view all the answers

What roles does histamine play in the gastric physiology?

Stimulates release of gastric acid and promotes vasodilation Signup and view all the answers

Which class of drug blocks the H+/K+ ATPase in the gastric acid secretion mechanism?

Proton pump inhibitors Signup and view all the answers

What stimulates parietal cells to secrete gastric acid?

Gastrin and Acetylcholine Signup and view all the answers

Where is histamine stored and released from in the stomach?

Enterochromaffin-like (ECL) cells Signup and view all the answers

Which receptor does gastrin act upon to stimulate gastric acid secretion?

CCK2 receptors Signup and view all the answers

Which mechanism describes the dissociation of water in gastric cells during acid secretion?

Water dissociating into H+ and OH- Signup and view all the answers

Which of the following statements about H2 receptor antagonists is correct?

They block H2 receptors Signup and view all the answers

What is the role of bicarbonate ions in the gastric acid secretion process?

They are formed from CO2 and OH- Signup and view all the answers

What is the primary area affected by H.pylori infections in the stomach?

Stomach antrum Signup and view all the answers

What is a significant consequence of long-standing H.pylori gastritis?

Gastric atrophy Signup and view all the answers

What type of immune cells primarily infiltrate the gastric mucosa during H.pylori infections?

Plasma cells Signup and view all the answers

Which condition is strongly associated with atrophic gastric epithelium due to H.pylori?

Gastric adenocarcinoma Signup and view all the answers

What diagnostic method involves detecting antibodies to H.pylori in the serum?

Serological test Signup and view all the answers

What clinical symptom may suggest a H.pylori infection?

Epigastric pain Signup and view all the answers

What is the role of neutrophils in H.pylori gastritis pathology?

Infiltrate the basement membrane and accumulate in gastric glands Signup and view all the answers

What can an overgrowth of MALT associated with H.pylori lead to?

Gastric lymphoma Signup and view all the answers

What is the primary function of histamine in gastric physiology?

Stimulates release of gastric acid Signup and view all the answers

What is the primary function of intrinsic factor in the digestive system?

Facilitates the absorption of vitamin B12 Signup and view all the answers

Which type of cell secretes gastrin in the stomach?

G cells Signup and view all the answers

What mechanism describes how bicarbonate ions are formed during gastric acid secretion?

By the reaction of CO2 with water in the cytoplasm Signup and view all the answers

Which cells are responsible for secreting pepsinogen in the stomach?

Chief cells Signup and view all the answers

Which receptor does acetylcholine act on to stimulate gastric acid secretion?

Muscarinic receptors Signup and view all the answers

What triggers the secretion of gastrin in the proximal intestine?

Presence of amino acids and partially digested peptides Signup and view all the answers

What is the main action of proton pump inhibitors in gastric physiology?

Blocks the H+/K+ ATPase Signup and view all the answers

What composition aids in protecting the gastric mucosa from acidity?

Bicarbonate microclimate and gastric mucin Signup and view all the answers

At what pH level is pepsin most active?

Optimal range of 1.8 to 3.5 Signup and view all the answers

Which class of receptors does histamine act on to promote acid secretion?

H2 receptors Signup and view all the answers

What is the role of Cl- ions in the secretion of gastric acid?

They are passively transported into the lumen of the canaliculus Signup and view all the answers

What is the role of secretin in gastric physiology?

Stimulates chief cells to release more pepsinogen Signup and view all the answers

What effect do H2 receptor antagonists have on gastric acid secretion?

They block the binding of histamine to its receptor Signup and view all the answers

Which factors contribute to the gastric diffusion barrier?

Mucus gel layer, bicarbonate microclimate, and tight junctions Signup and view all the answers

What is the main composition of the gastric gel layer that protects the stomach lining?

Mucins and bicarbonate Signup and view all the answers

What type of HLA molecules are primarily associated with the development of celiac disease?

HLA-DQ2 or HLA-DQ8 Signup and view all the answers

Which of the following is a primary antibody closely associated with celiac disease?

Anti-tissue transglutaminase antibodies (tTG) Signup and view all the answers

What consequence results from the destruction of enterocytes in celiac disease?

Malabsorption and nutrient deficiencies Signup and view all the answers

Which symptom is commonly observed in children with celiac disease?

Seizure disorders Signup and view all the answers

Which is considered the gold diagnostic standard for celiac disease?

Duodenal biopsy Signup and view all the answers

What is a major extra-intestinal manifestation of celiac disease?

Dermatitis herpetiformis Signup and view all the answers

Continuous exposure to gluten in individuals with celiac disease may lead to which progression?

Worsening of intestinal and extra-intestinal manifestations Signup and view all the answers

What do phagocytosing antigen-presenting cells (APCs) do with gliadin in celiac disease?

They present gliadin to Th cells to activate an immune response Signup and view all the answers

Which phase of gastric acid secretion is initiated by the smell, sight, taste, thought, and swallowing of food?

Cephalic phase Signup and view all the answers

What primarily mediates the cephalic phase of gastric acid secretion?

Vagus nerve Signup and view all the answers

What substance is released from G cells during the cephalic phase to stimulate gastric acid secretion?

Gastrin Signup and view all the answers

During the gastric phase, which reflex is activated by food entering the stomach?

Vagovagal reflex Signup and view all the answers

What effect does low luminal pH have on D cells during the gastric phase?

Stimulates somatostatin secretion Signup and view all the answers

Which mechanism explains how acetylcholine influences gastric acid secretion?

Acts on parietal cells Signup and view all the answers

What role do partially digested proteins play in the gastric phase of gastric acid secretion?

Activate G cells to produce gastrin Signup and view all the answers

What is the function of the vagus nerve during the cephalic phase?

Induces acetylcholine release Signup and view all the answers

What is a major complication of chronic gastritis?

Peptic ulcer disease Signup and view all the answers

Which type of peptic ulcer is more likely to be malignant?

Gastric ulcer Signup and view all the answers

What is the primary treatment regimen for H.pylori gastritis?

Triple therapy: two antibiotics + PPI Signup and view all the answers

How does acute gastritis differ from chronic gastritis in terms of immune cell presence?

Chronic gastritis has more plasma cells and lymphocytes than acute gastritis. Signup and view all the answers

What can chronic gastritis lead to regarding gastric epithelium?

Atrophy Signup and view all the answers

What is typically associated with duodenal ulcers?

Lower risk of perforation Signup and view all the answers

What factor contributes most commonly to peptic ulcer disease?

H.pylori infection Signup and view all the answers

What happens in the lamina propria during chronic gastritis?

Infiltration of plasma cells and lymphocytes Signup and view all the answers

What role do commensal bacteria like Firmicutes have in the immune system?

They enhance IgA production and Th17 development. Signup and view all the answers

What is one of the consequences of gliadin binding to the CXCR3 receptor?

Disassembly of zonula occludens proteins. Signup and view all the answers

What effect does the production of IL-15 by enterocytes have on intra-epithelial lymphocytes?

It causes them to express NK cell activating receptors. Signup and view all the answers

What is the impact of short-chain fatty acids (SCFAs) on dendritic cells?

They influence the induction of regulatory T-cells. Signup and view all the answers

What is a consequence of the disassembly of tight junctions due to gliadin exposure?

Increased permeability of the intestinal barrier. Signup and view all the answers

Which cells secrete gastrin in the stomach?

G cells Signup and view all the answers

What directly stimulates parietal cells to secrete gastric acid by binding to a specific receptor?

Histamine Signup and view all the answers

What feedback mechanism is involved in the secretion of somatostatin in response to luminal H+?

Negative feedback Signup and view all the answers

Which of the following substances inhibit gastric acid secretion?

Somatostatin Signup and view all the answers

What triggers the release of gastrin?

Vagal stimulation Signup and view all the answers

What characterizes acute erosive hemorrhagic gastritis?

Loss of superficial epithelium and occurrence of bleeding Signup and view all the answers

In cases of acute gastritis, what is typically present in the lamina propria?

Moderate edema and slight vascular congestion Signup and view all the answers

Which of the following symptoms may indicate acute gastritis?

Dyspepsia and acute abdominal pain Signup and view all the answers

What potential complication can arise from acute gastritis?

Perforation leading to peritonitis Signup and view all the answers

What is the initial histological change observed in acute gastritis?

Mild inflammation with neutrophils in the epithelium Signup and view all the answers

What is the primary function of the stomach in the gastrointestinal tract?

Reservoir for food and mixing with gastric juices Signup and view all the answers

Which of the following is NOT a main region of the stomach?

Transverse colon Signup and view all the answers

What are the two main curvatures of the stomach called?

Lesser and greater Signup and view all the answers

Which sphincter is located at the exit of the stomach leading to the small intestine?

Pyloric sphincter Signup and view all the answers

Which component of the stomach anatomy is primarily responsible for the production of chyme?

Body Signup and view all the answers

What is the primary structural feature that allows the stomach to accommodate a large quantity of food?

Elasticity of muscularis externa Signup and view all the answers

What is formed when saliva, food, and gastric juice mix in the stomach?

Chyme Signup and view all the answers

Which part of the stomach is primarily focused on the mixing process?

Fundus and body Signup and view all the answers

Which artery supplies blood to both the pancreas and the duodenum?

Pancreaticoduodenal artery Signup and view all the answers

Which part of the small intestine has the most prominent plicae circulares?

Jejunum Signup and view all the answers

What is the primary function of CCK (cholecystokinin)?

Inhibits gastric emptying Signup and view all the answers

What are the primary cell types found in the villi of the small intestine?

Enterocytes and Goblet cells Signup and view all the answers

What triggers the release of secretin?

Low pH in the small intestine Signup and view all the answers

How does the ileocecal sphincter function during increased pressure in the cecum?

It constricts to prevent backflow. Signup and view all the answers

What effect does peptide YY have on gastric motility?

Inhibits gastric motility. Signup and view all the answers

Which hormone is primarily responsible for stimulating pancreatic enzyme secretion?

Cholecystokinin (CCK) Signup and view all the answers

How are intestinal digestive juices primarily characterized?

Alkaline with a pH of 7.5 to 8.0 Signup and view all the answers

Which structure contributes to the absorption of nutrients in the small intestine?

Microvilli Signup and view all the answers

What role does the enteric nervous system play in peristalsis?

Mediates the peristaltic reflex Signup and view all the answers

What is the function of Brunner’s glands in the duodenum?

Secrete alkaline mucus to protect the duodenum Signup and view all the answers

What regulates the rate of gastric emptying through hormonal control?

Hormones released by enteroendocrine cells Signup and view all the answers

Study Notes

Immune Tolerance and the Microbiome

Commensal bacteria stimulate the development of regulatory T cells (Tregs), particularly from Firmicutes, Actinobacteria, and Bacteroidetes.
Short-chain fatty acids (SCFAs) produced by these bacteria influence dendritic cells, promoting the induction of Tregs.
Commensal bacteria aid in the development of mucosa-associated lymphoid tissue (MALT) through Toll-like receptor (TLR) signaling, resulting in secretion of IL-17, IL-22, and other MALT-promoting signals.
Segmented and filamentous bacteria (Firmicutes) enhance immunoglobulin A (IgA) production and promote Th17 cell development.

Failure of Tolerance: Celiac Disease

Celiac disease occurs due to gluten's interference with the intestinal immune system through a multi-step process.
Alpha-gliadin, a stable gluten degradation product, resists breakdown by pancreatic enzymes.
Gliadin binds to CXCR3 chemokine receptors, triggering the secretion of zonulin, leading to the disruption of tight junctions in the intestinal epithelium.
Gliadin also induces enterocytes to produce IL-15, causing intra-epithelial lymphocytes to activate NK cell receptors in response to stress proteins on enterocytes.
Inflammatory molecules, including gliadin, penetrate damaged tight junctions, exacerbating the immune response.

Stomach Anatomy

The stomach, a J-shaped structure, lies inferior to the diaphragm and is the most distensible part of the gastrointestinal (GI) tract, holding 0.8-1.5L of food.
Functions as a reservoir for food before it enters the small intestine, mixing food, saliva, and gastric juice to form chyme.
The stomach consists of four main regions: Cardia, Fundus, Body, and Pylorus.
Contains two main sphincters: lower esophageal and pyloric, which control food entry and prevent reflux.
Features two primary curvatures: Lesser and Greater.

Stomach Physiology: Motility

Food entry is facilitated by a wave of relaxation along the esophagus and stomach, triggered by swallowing and distension.
The fundus stores food until ready for processing, with the stomach wall bulging outward to accommodate larger food volumes.
Gastric accommodation reduces muscle tone in the stomach as it stretches.

Stomach Physiology: Secretions

Gastric acid secretion begins with the dissociation of water into H+ and OH-, with CO2 combining with OH- to form bicarbonate.
H+ ions are pumped into the canaliculus by H+/K+ ATPase, while Cl- ions passively move from the cytoplasm into the lumen.
Parietal cells are stimulated by acetylcholine, gastrin, and histamine to release gastric acid.
Histamine released from enterochromaffin-like cells enhances gastric acid secretion and vasodilation.

Chronic H. pylori Gastritis: Pathogenesis and Pathology

H. pylori typically infects the stomach antrum, promoting increased acid secretion and a risk of peptic ulcer disease.
Chronic infection may progress to gastric body and fundus, associated with gastric atrophy and increased risk of adenocarcinoma.
Pathological features include erythematous antral mucosa with plasma cells, lymphocytes, and mucosal infiltration leading to potential atrophic changes.
Overgrowth of MALT due to H. pylori may be related to gastric lymphoma.

Clinical Features and Diagnosis of Chronic H. pylori Gastritis

Clinical symptoms can be absent or include epigastric pain, nausea, vomiting, early satiety, and weight loss.
Diagnosis involves serological tests for H. pylori antibodies, detection of fecal bacteria, and urea breath tests.

Celiac Disease Pathogenesis

Antigen-presenting cells (APCs) phagocytose gliadin, which can activate Th cells (Th1 or Th17) through the expression of HLA-DQ2 or HLA-DQ8 molecules.
HLA-DQ2 or DQ8 is crucial for sustaining inflammation and villous destruction, strongly associated with celiac disease development.
Not all individuals with HLA-DQ2 or DQ8 develop celiac disease; ongoing research addresses this variability.
Pathogenesis involves enterocyte destruction by intra-epithelial lymphocytes, loss of tight junction integrity, and continuous gliadin-driven inflammation.
Results in self-antibody production, particularly tissue-transglutaminase antibodies, villous destruction, and crypt hyperplasia.

Celiac Disease Clinical Presentation

Adult symptoms: anemia, chronic diarrhea, bloating, fatigue, and nutrient deficiencies (B12 and iron).
Pediatric symptoms: irritability, anorexia, chronic diarrhea, weight loss, muscle wasting, and possible abdominal pain or constipation.
Children may not outwardly appear nutrient-deficient.
Extra-intestinal manifestations are common across all ages, including arthritis, stomatitis, and dermatitis herpetiformis (10% of patients).
In children, additional manifestations may include seizure disorders, pubertal delay, and short stature.

Celiac Disease Diagnosis and Prognosis

Diagnosis: Anti-tissue transglutaminase antibodies have over 95% specificity and sensitivity; duodenal biopsy is the gold standard.
Prognosis is generally excellent if gluten is strictly avoided; continued gluten exposure can lead to various manifestations and possible B-cell lymphoma development.

Gastric Acid Physiology

Gastric acid production begins with CO2 combining with OH- to create bicarbonate ions in parietal cells.
H+/K+ ATPase pumps hydrogen ions into the canaliculus, and chloride ions are passively transported into the lumen.
Parietal cell stimulation occurs via acetylcholine (muscarinic receptors), gastrin (CCK2 receptors), and histamine (H2 receptors).
Proton pump inhibitors block H+/K+ ATPase, reducing gastric acid secretion.

Gastric Acid Secretion Phases

Cephalic Phase: Triggered by sensory stimuli (sight, smell, taste). Accounts for 30% of total acid secretion, primarily mediated by the vagus nerve.
Gastric Phase: Food distends the stomach, activating the vagovagal reflex and local ENS reflexes. Accounts for 50-60% of secretion, with negative feedback mechanisms involving D cells.
Intestinal Phase: Presence of amino acids and peptides in the proximal intestine stimulates G cells to secrete gastrin, accounting for 5-10% of secretion.

Other Gastric Secretions

Intrinsic Factor: A glycoprotein essential for vitamin B12 absorption in the ileum, secreted by parietal cells.
Pepsinogen: Secreted by chief cells, converted to pepsin by HCl, aiding in protein digestion, dependent on low pH.

Gastric Mucosa Protection

Gastric diffusion barrier protects against low pH and high pepsin levels: includes mucus gel layer and tight junctions in gastric glands, maintaining a bicarbonate microclimate.

Gastritis and Peptic Ulcer Disease

Acute gastritis: Characterized by inflammation and neutrophil presence. Symptoms can include erosion and potential bleeding.
Chronic gastritis: Possesses more lymphocytes and plasma cells; can progress to atrophy and overgrowth of MALT.
Peptic ulcer disease arises from chronic gastritis, with duodenal ulcers being 4x more common than gastric ulcers, which have a higher risk of malignancy.
Etiology includes H. pylori infection, NSAIDs, and smoking, with H. pylori being the most common cause.

Immune Tolerance and the Microbiome

Commensals play a vital role in immune system regulation by promoting the development of regulatory T-cells (Tregs).
Key bacterial groups: Firmicutes, Actinobacteria, and Bacteroidetes contribute through short-chain fatty acids (SCFAs) affecting dendritic cells.
SCFAs are essential for stimulating Tregs and aiding the development of mucosa-associated lymphoid tissue (MALT) through TLR signaling.
Segmented and filamentous bacteria from Firmicutes enhance IgA production and promote Th17 cell development.

Celiac Disease: Mechanism of Immune Disruption

Alpha-gliadin, a gluten degradation product, resists pancreatic enzyme breakdown.
Gliadin binds to CXCR3 receptors, leading to zonulin production, which disrupts tight junctions by disassembling ZO proteins.
Internally, gluten triggers enterocytes to produce IL-15, activating intra-epithelial lymphocytes to express NK cell receptors, further damaging the intestinal environment.
Pro-inflammatory substances, including gliadin, can pass through compromised tight junctions, exacerbating the immune response.

Stomach Anatomy and Physiology

The stomach is a J-shaped organ located under the diaphragm, serving as a reservoir for food and mixing it with saliva and gastric juices to form chyme.
Major anatomical regions include the cardia, fundus, body, and pylorus, with two sphincters (lower esophageal and pyloric) and two curvatures (lesser and greater).
The stomach histology includes mucosa with gastric glands, submucosa, muscularis externa, and serosa.

Stomach Secretions and Function

Gastrin, produced by enteroendocrine cells, stimulates gastric acid secretion in response to stomach distension, vagal stimulation, and partially digested proteins.
Acid secretion from parietal cells can be inhibited by somatostatin and prostaglandins.
Somatostatin reduces gastric acid secretion and inhibits the release of various gastrointestinal hormones.

Gastritis: Acute and Chronic

Acute gastritis involves mild initial inflammation that can progress to severe erosive and hemorrhagic conditions.
Common clinical symptoms include dyspepsia, nausea, vomiting, and acute abdominal pain.
Chronic gastritis is prevalent and often linked to Helicobacter pylori infection.

Small Intestine Anatomy and Histology

The small intestine consists of three parts: duodenum, jejunum, and ileum, receiving arterial supply primarily from the superior mesenteric artery.
Histologically, the mucosa features simple columnar epithelium with villi and microvilli to increase absorptive surface area.
The submucosa contains plica circulares (permanent folds) and various glands specific to each section of the small intestine.

Movements and Motility of the Small Intestine

Mixing (segmentation) occurs through local reflex contractions that enhance exposure of chyme to digestive enzymes.
Propulsive movements (peristalsis) move chyme toward the anus, facilitated by both nervous and hormonal control.
Chyme is regulated in its entry to the duodenum to ensure optimal digestive function and prevent damage to intestinal lining.

Control of Gastric Emptying

Gastric emptying requires food particles to be small and released gradually to allow for proper digestion.
The duodenum plays a crucial role in regulating gastric emptying via both nervous and hormonal control, responding to factors like osmolarity and pH levels.
Key hormones involved include CCK, secretin, and peptide YY, which communicate nutritional status and digestive needs.

Secretions from the Small Intestine

Enterocytes produce digestive juices similar to extracellular fluid, facilitating nutrient absorption.
Brunner's glands in the duodenum secrete alkaline mucus that protects the intestinal lining from gastric acid damage.
Hormonal stimulation of digestive secretions is critical for maintaining intestinal health and promoting digestion.

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Description

This quiz explores the role of commensal bacteria in immune tolerance and the development of the microbiome. Topics include the influence of short-chain fatty acids and Toll-like receptor signaling on regulatory T-cell induction. Test your knowledge on the intricate relationship between gut microbiota and immune system functionality.