68 Questions
What is the estimated ratio of commensal bacteria to host cells in the human body?
10:1
What percentage of immune cells are located in the gut?
80%
What is the primary purpose of the physical barrier in maintaining the mucosal barrier?
To prevent pathogen entry
What is the consequence of a breakdown in tolerance in the immune system?
Autoimmune disease
What is the main cause of death in children under 5 years of age?
Mucosal infections
What is the role of gut-associated lymphoid tissues (GALT) in the immune system?
To induce immune responses
What is the role of IgM in a mild phenotype?
Compensates for other immune responses
What is the result of adherent or invasive bacteria in the epithelium?
Sustained TLR signals and inflammatory cytokines
What is the role of Th17 cells in the presence of TGFb, IL-6, and IL-1β?
They promote the expansion of Th17 cells
What is the effect of IL-22 on epithelial cells?
It increases epithelial permeability and allows transmigration of immune cells
What is the role of ILC2 cells in response to worm infections?
They recruit eosinophils to the site of infection
What is the primary function of mucosal surfaces?
They are the primary point of antigen entry
What is the primary function of IgA in the gut?
To neutralize potential pathogens without triggering damaging inflammatory responses
Which of the following is NOT a characteristic of Inflammatory Bowel Disease?
Autoimmune disease
What is the role of Peyer's patches in the gut?
To facilitate the isotype switching of B cells to IgA
What is the effect of Th17 cells in the presence of pathogens?
To attract neutrophils and enhance epithelial barrier repair
What is the approximate concordance rate of monozygotic twins with Crohn's Disease?
50%
Which of the following factors influences the development of Inflammatory Bowel Disease?
All of the above
Which type of immune cells are mainly involved in inflammatory bowel disease that affects the small intestine?
Th1 cells
What is the primary mechanism by which peripheral tolerance of B cells is induced?
Receptor editing of autoreactive B cells
Which type of hypersensitivity is characterized by the activation of neutrophils and the formation of crypt abscesses?
Type III hypersensitivity
What is the primary function of goblet cells in the intestinal mucosa?
Production of mucus
Which mechanism is responsible for the tolerance of commensal bacteria in the gut?
Induction of immune tolerance by dendritic cells
What is the primary difference between the mucosal immune response to commensal and pathogenic microbes?
Type of cytokines produced
What is the primary function of the tight junction proteins expressed by the intestinal epithelium?
To maintain an intact barrier to all but the smallest molecules
What type of cells are responsible for capturing antigens from the lumen and presenting them to T cells in Peyer's patches?
Dendritic cells and macrophages
What is the primary function of secretory IgA in the mucosal immune system?
To prevent bacterial adhesion to the mucosa and aid in the clearance of pathogens
What is the role of TGFb in the mucosal immune system?
To promote the differentiation of Tregs and induce tolerance
What is the primary function of the polymeric IgA receptor (pIgR) on epithelial cells?
To facilitate the transport of IgA into the lumen
What is the primary function of innate lymphoid cells (ILCs) in the mucosal immune system?
To secrete cytokines and activate immune responses
What is the main function of Peyer's patches in the mucosal immune system?
To develop IgA+ B cells in response to infection
What is the role of M cells in the mucosal immune system?
To sample antigens from the lumen and present them to APCs
What is the primary function of IL-10 in the mucosal immune system?
To promote the differentiation of Tregs and induce tolerance
What is the result of the activation of DCs and ILCs in the mucosal immune system?
The recruitment of ILCs and the secretion of cytokines
All of the secretory IgA produced in the gut lamina propria is transported to the lumen via transcytosis.
False
Tolerance in the gut is primarily mediated by TH17 cells.
False
M cells are a type of immune cell that can capture antigens from the lumen.
False
Dendritic cells in the gut produce primarily pro-inflammatory cytokines.
False
The polymeric IgA receptor is expressed on immune cells in the gut.
False
Innate lymphoid cells are primarily involved in adaptive immunity in the gut.
False
The tight junction proteins expressed by the intestinal epithelium are responsible for maintaining the physical barrier.
True
Goblet cells are responsible for producing IgA in the gut.
False
Peyer's patches are found in the colon and small intestine.
False
The majority of IgA in the body is produced in the gut.
True
In the presence of TGFb, IL-6, and IL-1β, Th1 cells are promoted.
False
IgA is involved in the activation of granulocyte degranulation.
False
IL-17A triggers antimicrobial peptide production from paneth cells and increases epithelial permeability.
False
ILC1 cells are involved in recruiting eosinophils to the site of infection during worm infections.
False
The primary function of Th17 cells is to induce tolerance in the mucosal immune system.
False
Mucosal surfaces are the primary point of antigen exit from the body.
False
The gut immune system is able to distinguish between pathogens and harmless antigens through the activation of TGFb and IL-6.
False
80% of immune cells are located in the skin.
False
Mucosal infections are the leading cause of death in children under 10 years of age.
False
Goblet cells are responsible for capturing antigens from the lumen and presenting them to T cells.
False
The physical barrier is the only system required to maintain the mucosal barrier.
False
Commensal bacteria outnumber host cells 5:1 in the human body.
False
Innate immunity at mucosal surfaces is primarily mediated by Tregs and Th17 cells.
False
IgA is primarily produced in response to pathogens and serves to trigger inflammatory responses.
False
Peyer's patches are sites of B cell isotype switching to IgM.
False
In the presence of pathogens, Th17 cells produce cytokines to attract macrophages and enhance epithelial barrier repair.
False
Inflammatory Bowel Disease is considered an autoimmune disease.
False
The concordance rate of monozygotic twins with Ulcerative Colitis is around 50%.
False
Inflammatory Bowel Disease mainly affects the small intestine and colon.
False
Tolerance in the gut is primarily mediated by Th1 cells.
False
The mucosal immune system responds to commensal and pathogenic microbes in the same way.
False
IgG is the primary immunoglobulin produced in the gut.
False
The breakdown of tolerance in the immune system leads to cancer.
False
The main function of Peyer's patches is to capture and present antigens from the lumen to T cells.
False
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.
-
Activation of DCs leads to recruitment of ILCs, which secrete further cytokines, and the cytokine environment can quickly activate DCs to produce inflammatory cytokines.
-
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.
-
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.
-
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.
-
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.
-
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.
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.
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