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Questions and Answers
What is one of the primary roles of enterocytes in the gut-associated lymphoid tissue (GALT)?
What is one of the primary roles of enterocytes in the gut-associated lymphoid tissue (GALT)?
Which type of cells in the lamina propria is most abundant in response to pathogens?
Which type of cells in the lamina propria is most abundant in response to pathogens?
What is the primary function of M cells in the gut?
What is the primary function of M cells in the gut?
What cytokine response is typically elicited by PRR engagement in enterocytes?
What cytokine response is typically elicited by PRR engagement in enterocytes?
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In the gut, which type of immune cell is primarily responsible for the first line of defense against pathogens?
In the gut, which type of immune cell is primarily responsible for the first line of defense against pathogens?
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What are the two major sections of the Gut-associated Lymphoid Tissue (GALT)?
What are the two major sections of the Gut-associated Lymphoid Tissue (GALT)?
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Which type of cells predominates in the gut epithelium and is primarily responsible for nutrient absorption?
Which type of cells predominates in the gut epithelium and is primarily responsible for nutrient absorption?
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What is the primary role of the mucus produced by goblet cells in the gut?
What is the primary role of the mucus produced by goblet cells in the gut?
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Which structures form the brush border in the gut epithelium?
Which structures form the brush border in the gut epithelium?
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What type of cells are located at the bottom of intestinal crypts and produce antimicrobial peptides?
What type of cells are located at the bottom of intestinal crypts and produce antimicrobial peptides?
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How do commensal organisms in the gut contribute to pathogen defense?
How do commensal organisms in the gut contribute to pathogen defense?
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What is the function of the glycocalyx associated with the brush border?
What is the function of the glycocalyx associated with the brush border?
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Which cells in the gut epithelium are important in integrating internal and external signals and coordinating immune responses?
Which cells in the gut epithelium are important in integrating internal and external signals and coordinating immune responses?
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Which epithelial cell type produces hormone-like molecules in the gut?
Which epithelial cell type produces hormone-like molecules in the gut?
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What is a characteristic of follicle associated epithelium (FAE) in the gut?
What is a characteristic of follicle associated epithelium (FAE) in the gut?
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What is an example of an inductive site in the mucosa where a primary adaptive immune response is initiated?
What is an example of an inductive site in the mucosa where a primary adaptive immune response is initiated?
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Which cells are involved in the local production of lymphotoxin (LT) and IL-17 that drive the development of induced MALT (iMALT)?
Which cells are involved in the local production of lymphotoxin (LT) and IL-17 that drive the development of induced MALT (iMALT)?
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What defines the local immune response of both mucosal and cutaneous immunity?
What defines the local immune response of both mucosal and cutaneous immunity?
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What term describes areas of induced MALT that can arise in the gut and lungs in response to infection and injury?
What term describes areas of induced MALT that can arise in the gut and lungs in response to infection and injury?
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Which type of mucosa is characterized by a single layer of columnar epithelium?
Which type of mucosa is characterized by a single layer of columnar epithelium?
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How do activated mucosal T and B cells reach various effector sites in the body?
How do activated mucosal T and B cells reach various effector sites in the body?
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What is a primary component of mucus that aids in immune function?
What is a primary component of mucus that aids in immune function?
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What is the significance of the 'common mucosal immune system' concept?
What is the significance of the 'common mucosal immune system' concept?
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Which statement accurately describes the role of antimicrobial peptides in mucosal immunity?
Which statement accurately describes the role of antimicrobial peptides in mucosal immunity?
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Which type of mucosal tissue is primarily associated with respiratory immunity?
Which type of mucosal tissue is primarily associated with respiratory immunity?
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What structure formed by the folding of the exterior surfaces of gut epithelium is key to nutrient absorption and pathogen defense?
What structure formed by the folding of the exterior surfaces of gut epithelium is key to nutrient absorption and pathogen defense?
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Which of the following functions is primarily associated with the goblet cells in the gut epithelium?
Which of the following functions is primarily associated with the goblet cells in the gut epithelium?
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How do enterocytes contribute to the immune response in the gut?
How do enterocytes contribute to the immune response in the gut?
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What type of surface covers the apical surfaces of gut epithelial cells that acts against ingested pathogens?
What type of surface covers the apical surfaces of gut epithelial cells that acts against ingested pathogens?
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Which of the following statements about the lamina propria is incorrect?
Which of the following statements about the lamina propria is incorrect?
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What distinguishes mucosal immunity from systemic immunity?
What distinguishes mucosal immunity from systemic immunity?
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Which of the following accurately describes a characteristic of type II mucosae?
Which of the following accurately describes a characteristic of type II mucosae?
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What role do antimicrobial molecules such as lysozyme and lactoferrin serve in mucosal immunity?
What role do antimicrobial molecules such as lysozyme and lactoferrin serve in mucosal immunity?
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What is the primary role of the brush border in the gut epithelium?
What is the primary role of the brush border in the gut epithelium?
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What is the primary function of the mucosa-associated lymphoid tissue (MALT)?
What is the primary function of the mucosa-associated lymphoid tissue (MALT)?
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Which feature characterizes the lamina propria within the GALT?
Which feature characterizes the lamina propria within the GALT?
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Which statement best describes the relationship between MALT and SALT in the immune system?
Which statement best describes the relationship between MALT and SALT in the immune system?
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Which of the following statements about the role of microbiota in the gut is accurate?
Which of the following statements about the role of microbiota in the gut is accurate?
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Which cell type is responsible for the production of mucus in the gut epithelium?
Which cell type is responsible for the production of mucus in the gut epithelium?
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What characteristic of the glycocalyx is essential for its function in the gut?
What characteristic of the glycocalyx is essential for its function in the gut?
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What primarily drives the ectopic development of lymphoid follicles and lymphatic vessels in induced MALT (iMALT)?
What primarily drives the ectopic development of lymphoid follicles and lymphatic vessels in induced MALT (iMALT)?
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Which of the following best describes a characteristic of inductive sites in the mucosa?
Which of the following best describes a characteristic of inductive sites in the mucosa?
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How do effector lymphocytes migrate to various effector sites after activation in an inductive site?
How do effector lymphocytes migrate to various effector sites after activation in an inductive site?
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What is the primary distinguishing feature of regions of mucosal-associated lymphoid tissue (MALT) that are linked to type 1 mucosa?
What is the primary distinguishing feature of regions of mucosal-associated lymphoid tissue (MALT) that are linked to type 1 mucosa?
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Which of the following statements accurately describes induced MALT (iMALT)?
Which of the following statements accurately describes induced MALT (iMALT)?
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Study Notes
Mucosal and Cutaneous Immunity
- Most human and animal pathogens enter the body through skin or mucosal surfaces.
- Mucosa-associated lymphoid tissue (MALT) and skin-associated lymphoid tissue (SALT) are collections of antigen-presenting cells (APCs) and lymphocytes.
- These tissues function independently and induce mucosal and cutaneous immune responses.
Mucosal Immunity Overview
- Mucosal Immunity is the immune response mounted at mucosal surfaces.
- The response is distinct from systemic immune responses and occurs locally where the antigen (Ag) is first encountered, without involvement of a draining lymph node).
- The effector cells can enter the lymphatic system or circulation but home to mucosal or cutaneous tissues.
Mucosal Immunity and Cutaneous Immunity
- Mucosal and cutaneous immune responses are different from systemic responses.
- The responses occur at the site of initial exposure to an Ag (antigen).
- Effector cells that are generated can enter efferent lymphatics or circulation, but they will specifically return to mucosal or cutaneous tissues to perform their effector functions.
- A systemic immune response can be triggered when antigen-bearing APCs of MALT or SALT migrate to local lymph nodes and activate naive B and T cells in that location.
Epithelial and Immune Function
- Mucosae come in two types:
- Type 1: Occurs in the intestine and lungs; composed of a single layer of columnar epithelium
- Type 2: Found in the mouth, nose, and vagina; uses squamous epithelium for a tougher tissue structure.
- Both types of mucosa produce mucus, which is a viscous solution of polysaccharides in water.
Mucus Composition
- Mucus contains various antibodies (Abs), mostly IgA in type 1 mucosae and IgG in type 2 mucosae.
- Contains antimicrobial molecules such as lysozyme (breaks down bacterial cell wall components) and lactoferrin (sequesters iron needed for bacterial growth).
MALT (Mucosa-Associated Lymphoid Tissue)
- MALT is a constantly being defended against pathogen assaults from immune responses mounted in MALT.
Inductive and Effector Sites
- An inductive site is an area in a mucosa where an antigen is encountered, leading to a primary adaptive immune response. (e.g. Peyer's Patches (PPs), in the gut)
- An effector site is an area where effector lymphocytes are dispatched. This could be an exocrine gland (e.g., salivary glands or lacrimal glands).
Components of GALT (Gut-Associated Lymphoid Tissue)
- GALT provides effective immune defense against ingested pathogens and toxins.
- Has two major sections: gut epithelium and lamina propria.
- Gut epithelium is folded into crypts and villi, and normal gut epithelium has follicle-associated epithelial (FAE) cells
- Lamina propria is loose connective tissue between the basolateral surfae of the epithelium and the muscle layer.
Elements of Gut Epithelium
- Enterocytes: Major portion, responsible for nutrient absorption.
- Enteroendocrine cells: Found in villi, produce mucus and hormone-like molecules.
- Paneth cells: Located in intestinal crypts, produce antimicrobial peptides.
- Goblet cells: Located on the sides of intestinal crypts, produce mucus and antimicrobial molecules.
Functions of GALT Components
- Mucus in GALT forms a strong physical barrier and antimicrobial defense.
- Gut epithelial cells' apical surfaces are protected by non-induced innate barriers.
- Commensal organisms compete for nutrients and space, limiting pathogenic encroachment.
- Beneficial microbiota secrete toxins that hinder pathogens and positively affect the underlying mucus layer.
- Brush border within GALT contains glycocalyx, which is a negative charge and repels pathogens
- TLRs, NLRs, and RLRs on enterocytes in GALT can respond to commensals or stress conditions through cytokine secretion.
- Additional innate defense in GALT is provided by γδ T cells within or near the epithelium; these cells produce antimicrobial peptides.
- NK cells and NKT cells in GALT participate in first-line defense.
Lamina Propria Components
- Lamina propria contains macrophages, neutrophils, NKT cells, mast cells, and immature DCs.
- Memory αβ T cells (both CD4+ and CD8+), memory B cells, and TH17 effectors are abundant.
- Some lymphocytes are diffusely distributed, while others organize into follicles.
Antigen Sampling in the Gut
- Follicle-associated epithelium (FAE) specializes in Ag capture.
- M cells, within FAE, directly transcytose antigens to other APCs in the dome.
- Interfollicular areas of FAE contain mature αβ T cells.
- Apical surfaces of M cells lack glycocalyx and have a thick brush border, which facilitates endocytosis of antigens.
GALT DCs
- Several DC subsets exist in mice, with CX3CR1+ DCs found throughout the gut.
- CX3CR1+ DCs directly sample Ag from the gut lumen and from M cells, while CCR6+ DCs mainly sample Ag from transcytosed M cells.
Immune Response Types
- In healthy conditions, GALT DCs will often provide tolerance or apoptosis for naïveT cells that respond to food antigens and promote Treg differentiation.
- During inflammation, GALT DCs mature and activate antigen-specific T cells. Activated DCs can migrate to draining lymph nodes to stimulate systemic immune responses.
NALT and BALT (Nasal-Associated Lymphoid Tissue and Bronchial-Associated Lymphoid Tissue)
- NALT and BALT defend against inhaled air substances and pathogens.
- NALT includes nasal submucosal glands, tonsils, and the epithelial layers lining the nasopharynx.
- BALT includes bronchial submucosal glands, epithelial layers lining the trachea, bronchi, and lungs, plus follicles and diffuse collections of lymphocytes beneath the epithelium.
- NALT and BALT have structures resembling those in the gut.
NALT and BALT Structure and Antigen Sampling
- Components of the upper respiratory system, like nose hairs and cillia in the nasal passages, provide non-induced innate barriers.
- Nasopharyngeal epithelial cells secrete sIgA, lactoferrin, lysozyme, and other antimicrobial molecules and maintain a normal microbiota.
- Under stress conditions, epithelial cells in NALT and BALT produce cytokines, which summon innate leukocytes.
- Unlike GALT, the uptake of antigens in NALT and BALT is easier due to a lack of harsh enzymes or low pH present in the gut.
Antigen Sampling and Response Types
- Antigen sampling in tonsils using M cells.
- Antigen sampling and responses in the airway that may use dendritic cells to convey antigens in the airway to the inductive sites.
- Dendritic cells that commence maturation can return to underlying lymphoid tissue or may migrate to more distant lymph nodes to induce a systemic response.
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Description
Test your knowledge on mucosal and cutaneous immunity, key concepts of how the body responds to pathogens that enter through skin or mucosal surfaces. Understand the roles of MALT and SALT, as well as the differences between local immune responses and systemic reactions.
