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Questions and Answers
What is the estimated ratio of commensal bacteria to host cells in the human body?
What is the estimated ratio of commensal bacteria to host cells in the human body?
What percentage of immune cells are located in the gut?
What percentage of immune cells are located in the gut?
What is the primary purpose of the physical barrier in maintaining the mucosal barrier?
What is the primary purpose of the physical barrier in maintaining the mucosal barrier?
What is the consequence of a breakdown in tolerance in the immune system?
What is the consequence of a breakdown in tolerance in the immune system?
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What is the main cause of death in children under 5 years of age?
What is the main cause of death in children under 5 years of age?
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What is the role of gut-associated lymphoid tissues (GALT) in the immune system?
What is the role of gut-associated lymphoid tissues (GALT) in the immune system?
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What is the role of IgM in a mild phenotype?
What is the role of IgM in a mild phenotype?
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What is the result of adherent or invasive bacteria in the epithelium?
What is the result of adherent or invasive bacteria in the epithelium?
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What is the role of Th17 cells in the presence of TGFb, IL-6, and IL-1β?
What is the role of Th17 cells in the presence of TGFb, IL-6, and IL-1β?
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What is the effect of IL-22 on epithelial cells?
What is the effect of IL-22 on epithelial cells?
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What is the role of ILC2 cells in response to worm infections?
What is the role of ILC2 cells in response to worm infections?
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What is the primary function of mucosal surfaces?
What is the primary function of mucosal surfaces?
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What is the primary function of IgA in the gut?
What is the primary function of IgA in the gut?
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Which of the following is NOT a characteristic of Inflammatory Bowel Disease?
Which of the following is NOT a characteristic of Inflammatory Bowel Disease?
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What is the role of Peyer's patches in the gut?
What is the role of Peyer's patches in the gut?
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What is the effect of Th17 cells in the presence of pathogens?
What is the effect of Th17 cells in the presence of pathogens?
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What is the approximate concordance rate of monozygotic twins with Crohn's Disease?
What is the approximate concordance rate of monozygotic twins with Crohn's Disease?
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Which of the following factors influences the development of Inflammatory Bowel Disease?
Which of the following factors influences the development of Inflammatory Bowel Disease?
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Which type of immune cells are mainly involved in inflammatory bowel disease that affects the small intestine?
Which type of immune cells are mainly involved in inflammatory bowel disease that affects the small intestine?
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What is the primary mechanism by which peripheral tolerance of B cells is induced?
What is the primary mechanism by which peripheral tolerance of B cells is induced?
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Which type of hypersensitivity is characterized by the activation of neutrophils and the formation of crypt abscesses?
Which type of hypersensitivity is characterized by the activation of neutrophils and the formation of crypt abscesses?
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What is the primary function of goblet cells in the intestinal mucosa?
What is the primary function of goblet cells in the intestinal mucosa?
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Which mechanism is responsible for the tolerance of commensal bacteria in the gut?
Which mechanism is responsible for the tolerance of commensal bacteria in the gut?
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What is the primary difference between the mucosal immune response to commensal and pathogenic microbes?
What is the primary difference between the mucosal immune response to commensal and pathogenic microbes?
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What is the primary function of the tight junction proteins expressed by the intestinal epithelium?
What is the primary function of the tight junction proteins expressed by the intestinal epithelium?
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What type of cells are responsible for capturing antigens from the lumen and presenting them to T cells in Peyer's patches?
What type of cells are responsible for capturing antigens from the lumen and presenting them to T cells in Peyer's patches?
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What is the primary function of secretory IgA in the mucosal immune system?
What is the primary function of secretory IgA in the mucosal immune system?
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What is the role of TGFb in the mucosal immune system?
What is the role of TGFb in the mucosal immune system?
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What is the primary function of the polymeric IgA receptor (pIgR) on epithelial cells?
What is the primary function of the polymeric IgA receptor (pIgR) on epithelial cells?
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What is the primary function of innate lymphoid cells (ILCs) in the mucosal immune system?
What is the primary function of innate lymphoid cells (ILCs) in the mucosal immune system?
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What is the main function of Peyer's patches in the mucosal immune system?
What is the main function of Peyer's patches in the mucosal immune system?
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What is the role of M cells in the mucosal immune system?
What is the role of M cells in the mucosal immune system?
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What is the primary function of IL-10 in the mucosal immune system?
What is the primary function of IL-10 in the mucosal immune system?
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What is the result of the activation of DCs and ILCs in the mucosal immune system?
What is the result of the activation of DCs and ILCs in the mucosal immune system?
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All of the secretory IgA produced in the gut lamina propria is transported to the lumen via transcytosis.
All of the secretory IgA produced in the gut lamina propria is transported to the lumen via transcytosis.
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Tolerance in the gut is primarily mediated by TH17 cells.
Tolerance in the gut is primarily mediated by TH17 cells.
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M cells are a type of immune cell that can capture antigens from the lumen.
M cells are a type of immune cell that can capture antigens from the lumen.
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Dendritic cells in the gut produce primarily pro-inflammatory cytokines.
Dendritic cells in the gut produce primarily pro-inflammatory cytokines.
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The polymeric IgA receptor is expressed on immune cells in the gut.
The polymeric IgA receptor is expressed on immune cells in the gut.
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Innate lymphoid cells are primarily involved in adaptive immunity in the gut.
Innate lymphoid cells are primarily involved in adaptive immunity in the gut.
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The tight junction proteins expressed by the intestinal epithelium are responsible for maintaining the physical barrier.
The tight junction proteins expressed by the intestinal epithelium are responsible for maintaining the physical barrier.
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Goblet cells are responsible for producing IgA in the gut.
Goblet cells are responsible for producing IgA in the gut.
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Peyer's patches are found in the colon and small intestine.
Peyer's patches are found in the colon and small intestine.
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The majority of IgA in the body is produced in the gut.
The majority of IgA in the body is produced in the gut.
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In the presence of TGFb, IL-6, and IL-1β, Th1 cells are promoted.
In the presence of TGFb, IL-6, and IL-1β, Th1 cells are promoted.
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IgA is involved in the activation of granulocyte degranulation.
IgA is involved in the activation of granulocyte degranulation.
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IL-17A triggers antimicrobial peptide production from paneth cells and increases epithelial permeability.
IL-17A triggers antimicrobial peptide production from paneth cells and increases epithelial permeability.
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ILC1 cells are involved in recruiting eosinophils to the site of infection during worm infections.
ILC1 cells are involved in recruiting eosinophils to the site of infection during worm infections.
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The primary function of Th17 cells is to induce tolerance in the mucosal immune system.
The primary function of Th17 cells is to induce tolerance in the mucosal immune system.
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Mucosal surfaces are the primary point of antigen exit from the body.
Mucosal surfaces are the primary point of antigen exit from the body.
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The gut immune system is able to distinguish between pathogens and harmless antigens through the activation of TGFb and IL-6.
The gut immune system is able to distinguish between pathogens and harmless antigens through the activation of TGFb and IL-6.
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80% of immune cells are located in the skin.
80% of immune cells are located in the skin.
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Mucosal infections are the leading cause of death in children under 10 years of age.
Mucosal infections are the leading cause of death in children under 10 years of age.
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Goblet cells are responsible for capturing antigens from the lumen and presenting them to T cells.
Goblet cells are responsible for capturing antigens from the lumen and presenting them to T cells.
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The physical barrier is the only system required to maintain the mucosal barrier.
The physical barrier is the only system required to maintain the mucosal barrier.
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Commensal bacteria outnumber host cells 5:1 in the human body.
Commensal bacteria outnumber host cells 5:1 in the human body.
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Innate immunity at mucosal surfaces is primarily mediated by Tregs and Th17 cells.
Innate immunity at mucosal surfaces is primarily mediated by Tregs and Th17 cells.
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IgA is primarily produced in response to pathogens and serves to trigger inflammatory responses.
IgA is primarily produced in response to pathogens and serves to trigger inflammatory responses.
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Peyer's patches are sites of B cell isotype switching to IgM.
Peyer's patches are sites of B cell isotype switching to IgM.
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In the presence of pathogens, Th17 cells produce cytokines to attract macrophages and enhance epithelial barrier repair.
In the presence of pathogens, Th17 cells produce cytokines to attract macrophages and enhance epithelial barrier repair.
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Inflammatory Bowel Disease is considered an autoimmune disease.
Inflammatory Bowel Disease is considered an autoimmune disease.
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The concordance rate of monozygotic twins with Ulcerative Colitis is around 50%.
The concordance rate of monozygotic twins with Ulcerative Colitis is around 50%.
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Inflammatory Bowel Disease mainly affects the small intestine and colon.
Inflammatory Bowel Disease mainly affects the small intestine and colon.
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Tolerance in the gut is primarily mediated by Th1 cells.
Tolerance in the gut is primarily mediated by Th1 cells.
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The mucosal immune system responds to commensal and pathogenic microbes in the same way.
The mucosal immune system responds to commensal and pathogenic microbes in the same way.
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IgG is the primary immunoglobulin produced in the gut.
IgG is the primary immunoglobulin produced in the gut.
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The breakdown of tolerance in the immune system leads to cancer.
The breakdown of tolerance in the immune system leads to cancer.
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The main function of Peyer's patches is to capture and present antigens from the lumen to T cells.
The main function of Peyer's patches is to capture and present antigens from the lumen to T cells.
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Study Notes
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The intestinal mucosa is a semi-permeable barrier composed of compacted glycoproteins, anti-microbial peptides, and secretory IgA, which provides protection against pathogens and maintains an intact barrier to all but the smallest molecules.
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The intestinal epithelium (enterocytes) expresses tight junction proteins to maintain an intact barrier and secretes MUC2, a glycoprotein that forms the mucus layer.
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Innate immune cells, including dendritic cells (DCs), macrophages, and innate lymphoid cells (ILCs), are present in close proximity to the epithelium, where they can capture antigens from the lumen and respond to cytokine signals.
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DCs and macrophages can capture antigens from the lumen by reaching between enterocytes while maintaining tight-junctional integrity, and are highly endocytic, with many pattern recognition receptors (PRRs) important for clearing bacteria and apoptotic/senescent cells.
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Mucosal DCs preferentially produce IL-10 and TGF-β, which are tolerogenic (anti-inflammatory) and promote differentiation of Tregs and class-switching to IgA.
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Activation of DCs leads to recruitment of ILCs, which secrete further cytokines, and the cytokine environment can quickly activate DCs to produce inflammatory cytokines.
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Peyer's patches are lymphoid aggregates found in the small intestine, where antigens enter via specialized epithelial cells called microfold (M) cells, and are collected by a sub-epithelial network of antigen-presenting cells (APCs), including DCs and macrophages.
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Germinal centers of lymphoid follicles contain populations of B cells undergoing isotype switching and somatic hypermutation, with the main function of developing IgA+ B cells in response to infection.
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Secretory IgA is produced as a dimer linked by the J chain from plasma B cells beneath the epithelium, and is transported into the lumen via the polymeric IgA receptor (pIgR) on epithelial cells.
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Secretory IgA prevents bacterial adhesion to the mucosa, aids in the clearance of pathogens, and neutralizes pathogens and toxins, with over 75% of Ig in the body being IgA, most of which is secreted at mucosal membranes.
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IgA deficiency is the most common human immunodeficiency, but has a relatively mild phenotype, with IgM compensating to some extent.
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The gut immune system distinguishes between pathogens and harmless antigens through a balance of immune responses, including the physical barrier, innate immunity, and adaptive immunity.
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Mucosal surfaces are the primary point of entry for most pathogens, and mucosal infections are the main cause of death in children under 5 years of age.
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The gut has a large population of FoxP3+ Tregs, which are maintained by tolerogenic DCs, and Th17 cells produce cytokines (IL-17, IL-22) to attract neutrophils and enhance epithelial barrier repair in response to pathogens.
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Inflammatory bowel disease (IBD) is a multifactorial disease with unknown etiologies, influenced by genetics, microorganisms, and environmental factors, and is characterized by a disruption of the mucosal barrier and inflammatory responses.
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Crohn's disease mainly affects the small intestine, with a Th1/Th17 response, neutrophil infiltrate, disruption of the mucosal barrier, and granuloma formation, while ulcerative colitis mainly affects the colon, with a mixed Th1/Th2 response.
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Description
Test your understanding of immunological tolerance, hypersensitivity responses, and mucosal immunity. Explore the mechanisms of central and peripheral tolerance, autoimmune diseases, and the different types of hypersensitivity responses.
