Podcast
Questions and Answers
What is the primary role of Peyer's patches in the gut?
What is the primary role of Peyer's patches in the gut?
Which type of lymphoid tissue is exclusively found in the small intestine?
Which type of lymphoid tissue is exclusively found in the small intestine?
What characterizes the effector mechanisms of the mucosal immune system?
What characterizes the effector mechanisms of the mucosal immune system?
How does the mucosal immune system regulate responses to harmless antigens?
How does the mucosal immune system regulate responses to harmless antigens?
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What type of antibodies predominantly support mucosal immunity?
What type of antibodies predominantly support mucosal immunity?
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Where are isolated lymphoid follicles located?
Where are isolated lymphoid follicles located?
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What is a distinctive anatomical feature of the mucosal immune system?
What is a distinctive anatomical feature of the mucosal immune system?
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Which of the following structures is NOT part of the Gut Associated Lymphoid Tissue (GALT)?
Which of the following structures is NOT part of the Gut Associated Lymphoid Tissue (GALT)?
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What is the primary function of the thymus in relation to T cells?
What is the primary function of the thymus in relation to T cells?
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What type of cells are primarily found in the thymus?
What type of cells are primarily found in the thymus?
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Which of the following lymphoid organs is essential for the encounter between lymphocytes and antigens?
Which of the following lymphoid organs is essential for the encounter between lymphocytes and antigens?
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How does lymphatic fluid contribute to the immune response?
How does lymphatic fluid contribute to the immune response?
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What role do dendritic cells play in the lymphatic system?
What role do dendritic cells play in the lymphatic system?
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What is the purpose of positive and negative selection in the thymus?
What is the purpose of positive and negative selection in the thymus?
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Where do naïve lymphocytes populate after exiting the thymus?
Where do naïve lymphocytes populate after exiting the thymus?
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What is the primary component of lymphatic fluid?
What is the primary component of lymphatic fluid?
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What is the primary function of microfold cells (M cells) in the gut?
What is the primary function of microfold cells (M cells) in the gut?
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Where are isolated lymphoid follicles most frequently found?
Where are isolated lymphoid follicles most frequently found?
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What do M cells lack compared to conventional intestinal epithelial cells?
What do M cells lack compared to conventional intestinal epithelial cells?
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What role do macrophages and dendritic cells play related to M cells?
What role do macrophages and dendritic cells play related to M cells?
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What initiates the development of isolated lymphoid follicles after birth?
What initiates the development of isolated lymphoid follicles after birth?
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How do pathogens utilize M cells in the gut?
How do pathogens utilize M cells in the gut?
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Which immune response is initiated by dendritic cells and primed T cells?
Which immune response is initiated by dendritic cells and primed T cells?
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Which lymph nodes play a crucial role in shaping immune responses to intestinal antigens?
Which lymph nodes play a crucial role in shaping immune responses to intestinal antigens?
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What is the primary type of T cell found in the epithelium of the small intestine?
What is the primary type of T cell found in the epithelium of the small intestine?
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What is the main function of type a CD8 T cells in the intestinal epithelium?
What is the main function of type a CD8 T cells in the intestinal epithelium?
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Which form does IgA primarily take in mucosal tissues?
Which form does IgA primarily take in mucosal tissues?
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How is IgA transported across the epithelium to reach its target antigen in the gut lumen?
How is IgA transported across the epithelium to reach its target antigen in the gut lumen?
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What role do tight junction proteins play in the mucosal barrier?
What role do tight junction proteins play in the mucosal barrier?
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What is the primary function of type b CD8 T cells in the intestinal epithelium?
What is the primary function of type b CD8 T cells in the intestinal epithelium?
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Which immune cell type in the lamina propria is primarily responsible for producing IgA?
Which immune cell type in the lamina propria is primarily responsible for producing IgA?
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What is the main characteristic of the mucosal immune system even in the absence of disease?
What is the main characteristic of the mucosal immune system even in the absence of disease?
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What is the purpose of mucus production in the intestinal epithelium?
What is the purpose of mucus production in the intestinal epithelium?
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Which cytokines are known to be potent inflammatory and repair agents protecting intestinal crypts?
Which cytokines are known to be potent inflammatory and repair agents protecting intestinal crypts?
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What role do Paneth cells play in the intestinal epithelium?
What role do Paneth cells play in the intestinal epithelium?
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Which TLRs are present on the intestinal epithelial cells?
Which TLRs are present on the intestinal epithelial cells?
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NOD2 is specifically known for recognizing which molecular structure?
NOD2 is specifically known for recognizing which molecular structure?
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How does NOD1 differentiate between bacteria?
How does NOD1 differentiate between bacteria?
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What is the primary function of enteroendocrine cells within the intestinal epithelium?
What is the primary function of enteroendocrine cells within the intestinal epithelium?
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Which role does the gut microbiota play regarding the immune system?
Which role does the gut microbiota play regarding the immune system?
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Study Notes
Thymus
- Attracts circulating T cell precursors from bone marrow
- Essential for T cell maturation
- Composed of cortical and medullary epithelial cells, stromal cells, interdigitating cells and macrophages
- Important for T cell precursor differentiation and education (positive and negative selection)
Secondary/Peripheral Lymphoid Organs
- Lymph nodes
- Spleen
- Mucosal Associated Lymphoid Tissue (MALT)
Lymphocyte-Antigen Encounter
- Occurs in peripheral lymphoid organs
Lymph Node
- Lymphatics drain extracellular fluid from peripheral tissues
- Lymph carries antigen taken up by dendritic cells and macrophages to lymph nodes
- Lymph carries recirculating lymphocytes from lymph nodes back into blood
Mucosal Associated Lymphoid Tissue (MALT)
- Nasal associated lymphoid tissue (NALT)
- Bronchus associated lymphoid tissue (BALT)
- Gut associated lymphoid tissue (GALT)
Distinctive Features of the Mucosal Immune System
- Intimate interactions between mucosal epithelia and lymphoid tissues
- Discrete compartments of diffuse lymphoid tissue and more organized structures like Peyer's patches and isolated lymphoid follicles
- Specialized antigen-uptake mechanisms, e.g., M cells in Peyer's patches
- Activated/memory T cells predominate even in the absence of infection
- Secretory IgA antibodies
- Presence of distinctive microbiota
- Active downregulation of immune responses predominates
GALT
- Peyer's patches - only in the small intestine
- Isolated lymphoid follicles - entire intestine
- Appendix
- Tonsil and adenoid - in throat
Peyer's Patches
- Important sites for the initiation of immune responses in the gut
- 100-200 Peyer's patches in the human small intestine
- Visible to the naked eye, dome-like structure projecting into the intestinal lumen
- Contain B cells in B cell follicles, intercalated by T cell zones and dendritic cells
- Follicle-associated epithelium separates the lymphoid tissue from the gut lumen
M Cells
- Have a folded luminal surface instead of microvilli
- Do not secrete digestive enzymes or mucins
- Directly exposed to microorganisms and particles within the gut lumen
- Bind microbes and internalize them by transcytosis
- Provide a conduit for luminal microbes into the GALT and connected lymphatics
- Targeted by pathogens to gain access to the subepithelial space
Mesenteric Lymph Nodes
- Tissues of the small intestine drain to the mesenteric lymph nodes
- Largest lymph nodes in the body, crucial for initiating and shaping immune responses to intestinal antigens
- Mucosal surface and lymphoid aggregates of the large intestine drain to the mesenteric lymph nodes and the caudal lymph node
Mucosal Immune System
- Contains large numbers of effector lymphocytes even in the absence of disease
- Effector cells are found in two main compartments: the epithelium and the lamina propria
Intraepithelial lymphocytes (IEL)
- Lymphoid component of the epithelium consists mainly of lymphocytes, which are predominantly CD8 T cells, also called IEL
- Type a: express α:β T-cell receptors and CD8α:β heterodimer, possess cytolytic functions like antiviral activity and IFN-γ secretion
- Type b: express α:β or γ:δ T-cell receptors and CD8α:α heterodimer, involved in mucosal repair after inflammatory damage and stimulation of antimicrobial peptide release
IgA
- Dominant class of antibody in the mucosal immune system
- Produced locally by plasma cells in the mucosal wall
- Different forms in the blood and mucosal secretions
- IgA in blood is mainly a monomer
- In mucosal tissues, IgA is almost exclusively a polymer, usually a dimer
- Transported across epithelium by the polymeric immunoglobulin receptor (pIgR) via transcytosis to reach its target antigen
- Functions in various ways
Innate Immunity in the Gut
- Physical barrier: thin layer of permeable epithelium protects underlying tissues, tight junction proteins maintain paracellular permeability
- Mucus layer: large glycoproteins (secreted and membrane-bound) called mucins provide viscosity and protective properties
- Epithelial cells have immunological functions: sloughing, mucus production, antimicrobial peptides (AMPs), cytokines and chemokines, T cell-like cytokines
Intestinal Epithelial Cells (IECs)
- Enterocytes: absorption, mucus, digestive enzymes
- Enteroendocrine cells: hormone production, stem cell factors
- Goblet cells: specialized mucus producers
- Paneth cells: specialized cells defending the crypts in the small intestine and colon
- M cells: antigen and microbe passage to GALT
TLRs on IECs
- Epithelial cells express Toll-like Receptors (TLRs) on both apical and basal surfaces
- Sense bacteria in the gut lumen and those that have penetrated the epithelium
NOD Proteins
- NOD1 and NOD2 act as sensors
- NOD1 recognizes a diaminopimelic acid-containing peptide found in Gram-negative bacteria
- NOD2 recognizes muramyl dipeptide found in most bacterial peptidoglycans
- NOD2 dysfunction is associated with Crohn’s disease
Gut Microbiota and Functions
- 1014 microbes colonize the GI tract
- Immune response against these microbes is proactive, involving a constant adaptive response
- Inflammation is used sparingly
Cytokines
- Polypeptides secreted by leukocytes and other cells that act on hematopoietic cells
- Modulate immune and inflammatory responses
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Description
Test your knowledge on the role of the thymus and peripheral lymphoid organs in the immune system. This quiz covers T cell maturation, lymphocyte encounters, and the functions of various lymphoid tissues. Prepare to explore the intricacies of the mucosal immune system and how it interacts with antigens.
