WEEK 1: Immunology of the gut Flashcards
Interior of the body interacts with the external environment through mucosal surfaces.
What is mucosa?
State the different types of mucosal surfaces in the body?
A membrane rich in mucous glands.
*Gastrointestinal tract
*Respiratory tract
*Urinogenital tract
Mucosal Immune System
Mucosal membranes are major entry points of pathogens (particularly vulnerable to infection). They require specialized defensive systems.
Name the immunity found the mucosal surfaces.
Mucosal Immune System
Describe the Structure of the mucosa of the small intestine.
- Consists of finger-like processes (villi) covered by a layer of thin epithelial cells (red). Outline the cell types in the epithelium and their functions.
CELLS IN THE EPITHELIUM
1. M cells:
Function: These specialized epithelial cells are found in the mucosa-associated lymphoid tissue (MALT) and are responsible for transporting antigens from the gut lumen to underlying immune cells, thus initiating immune responses against pathogens.
- Goblet cells:
Function: Goblet cells produce and secrete mucus, which forms a protective layer over the epithelial surface of the intestine.
This mucus helps lubricate the intestinal lining and provides a barrier against pathogens and mechanical damage. - Paneth cells:
Function: Located in the crypts of Lieberkühn in the small intestine, Paneth cells secrete antimicrobial peptides (such as defensins and lysozyme) and proteins, which help to regulate the gut microbiota, protect against pathogens, and maintain intestinal homeostasis. - Intraepithelial lymphocytes:
Function: These are a subset of lymphocytes residing within the epithelial layer of the intestine.
IELs play important roles in immune surveillance, responding rapidly to infections or tissue damage, and maintaining immune tolerance to harmless antigens.
- Intestinal epithelial cells (Enterocytes):
Function:
*Enterocytes are the most abundant cell type in the intestinal epithelium.
*They are responsible for absorbing nutrients, electrolytes, and water from the gut lumen into the bloodstream.
*Additionally, enterocytes contribute to the physical barrier of the intestine and participate in immune responses by expressing pattern recognition receptors and secreting cytokines in response to pathogens.
Describe the Structure of the mucosa of the small intestine.
The tissue layer under the epithelium is the lamina propria.
Outline all the structures found in the lamina propria and their functions.
- Blood vessels:
Function: Blood vessels in the lamina propria, including capillaries and venules, provide a route for the transport of absorbed nutrients and oxygen to the surrounding tissues, as well as the removal of waste products. - Lymphatic vessels (Lacteals):
Function: Lymphatic vessels, known as lacteals in the small intestine, absorb dietary fats and fat-soluble vitamins (such as vitamins A, D, E, and K) from the intestinal lumen and transport them to the bloodstream via the lymphatic system.
*Lymphatics arising in the lamina propria drain to the mesenteric lymph nodes.
- Lymphoid follicles (Peyer’s patches):
Function: These are aggregated lymphoid nodules located in the lamina propria and submucosa of the small intestine, particularly in the ileum.
Peyer’s patches are important sites of immune surveillance.
and defense, containing specialized immune cells such as B cells, T cells, and antigen-presenting cells.
They play a crucial role in initiating immune responses against pathogens and maintaining immune tolerance to harmless antigens.
Antigen enters a Peyer’s patch from the gut via the M cells. Peyer’s patches have no afferent lymphatics, but they are a source of efferent lymphatics that connect with the lymphatics carrying lymph to the mesenteric lymph node
- Plasma cells:
Function: Plasma cells are specialized immune cells derived from activated B lymphocytes.
They are responsible for producing and secreting immunoglobulins (antibodies), which play a critical role in neutralizing pathogens and toxins in the intestinal lumen, thus contributing to mucosal immunity.
- Macrophages:
Function: Macrophages are phagocytic immune cells that engulf and digest pathogens, cellular debris, and foreign particles in the lamina propria.
*They also function as antigen-presenting cells, presenting antigenic peptides to T lymphocytes and initiating adaptive immune responses.
- Dendritic cells:
Function: Dendritic cells are antigen-presenting cells that play a key role in immune surveillance and tolerance in the intestinal mucosa. They capture antigens from the gut lumen and transport them to lymphoid tissues, where they activate T cells and initiate adaptive immune responses. - Fibroblasts:
Function: Fibroblasts are connective tissue cells found in the lamina propria that produce and maintain the extracellular matrix, providing structural support and elasticity to the intestinal mucosa. - Smooth muscle cells:
Function: Smooth muscle cells are present in the lamina propria of the small intestine, where they regulate the contraction and relaxation of the muscularis mucosae, facilitating the movements of the intestinal villi and aiding in nutrient absorption and peristalsis.
What is the process that M cells use to transfer pathogens from the epithelium to the peyers patch called?
TRANSCYTOSIS
-M cells possess specialized structures on their apical surface that facilitate the uptake of luminal contents, including pathogens, through transcytosis.
-Once internalized, the pathogens are encapsulated within vesicles and transported across the M cell to the basal side, where they are released into the subepithelial dome region of the Peyer’s patch.
-This process allows for the efficient delivery of antigens from the gut lumen to the underlying immune cells within the Peyer’s patch, initiating immune responses against pathogens.
What are lymphoid organs?
Describe the 2 main types of lymphoid organs and give examples..
Lymphoid organs are parts of the lymphatic system where lymphocytes (a type of white blood cell) mature, proliferate, and carry out immune responses.
- Primary Lymphoid Organs:
*These organs are where immature lymphocytes develop and mature into functional immune cells.
Examples include the bone marrow and the thymus gland.
In the bone marrow, B lymphocytes (B cells) undergo maturation, while in the thymus, T lymphocytes (T cells) mature and develop functional capabilities.
- Secondary Lymphoid Organs:
*These organs are where mature lymphocytes encounter antigens, undergo activation, and initiate immune responses.
Examples include lymph nodes, spleen, tonsils, and mucosa-associated lymphoid tissues (MALT) such as Peyer’s patches in the small intestine and the appendix.
In secondary lymphoid organs, lymphocytes interact with antigen-presenting cells and other immune cells, leading to the initiation of adaptive immune responses against pathogens.
Give examples of secondary lymphoid organs according to the following categories.
- To antigens in tissues
- To antigens in blood
- To antigens in mucosal surfaces
- To antigens in tissues
-Lymph nodes - To antigens in blood.
-Spleen - To antigens in mucosal surfaces
-GALT (Gut-Associated Lymphoid Tissue): Found in the gastrointestinal tract, particularly in the intestines.
-MALT (Mucosa-Associated Lymphoid Tissue):
MALT refers to lymphoid tissues associated with mucosal surfaces throughout the body.
from GALT in the gut, MALT includes structures in other mucosal sites such as the respiratory tract, genitourinary tract, and mucosal surfaces of the eyes.
-BALT (Bronchus-Associated Lymphoid Tissue):
Found in the respiratory tract, particularly in the bronchi and bronchioles of the lungs.
Discuss the innate immune responses of the gut.
- Stomach Acid:
Function: Creates an acidic environment in the stomach, which helps to kill ingested pathogens and bacteria, thus serving as a primary defense mechanism against infections. - Mucus (+Antibacterial Molecules):
*Mucus forms a protective layer over the epithelial cells lining the gastrointestinal tract.
*It traps pathogens and prevents them from directly contacting the epithelial surface.
*Additionally, mucus contains antibacterial molecules (such as defensins and lysozyme) that help to inhibit the growth of bacteria and other microorganisms.
- Barrier (Commensal Bacteria):
-The presence of commensal bacteria in the gastrointestinal tract helps to maintain a healthy microbial balance (microbiota) and competes with potential pathogens for resources, thus preventing colonization by harmful microbes.
-Commensal bacteria also play important roles in immune regulation and nutrient metabolism.
- Epithelial Cells (+Mucin):
Function: Intestinal epithelial cells form a physical barrier between the gut lumen and the underlying tissues.
They are covered by a layer of mucus (containing mucin), which further enhances the barrier function by trapping pathogens and preventing direct contact with the epithelial surface.
- Paneth Cells (Antimicrobial Peptides):
Function: Paneth cells are specialized epithelial cells found in the crypts of Lieberkühn in the small intestine.
They secrete antimicrobial peptides (such as defensins and lysozyme) that help to regulate the gut microbiota, protect against pathogens, and maintain intestinal homeostasis.
- Innate Cells (e.g., Phagocytic Macrophages):
Function: Phagocytic macrophages are immune cells found in the lamina propria and submucosa of the gastrointestinal tract.
*They engulf and digest pathogens, cellular debris, and foreign particles, thus playing a crucial role in innate immune defense against infections.
*Additionally, macrophages contribute to tissue repair and immune regulation in the gut.
Discuss the adaptive immunity of the gut.
T cells.
T Cells:
T lymphocytes, or T cells, are a type of white blood cell that plays a central role in adaptive immune responses.
In the gut, various subsets of T cells, including CD4+ T helper cells and CD8+ cytotoxic T cells, are present.
CD4+ T helper cells can differentiate into distinct subsets, such as Th1, Th2, Th17, and regulatory T cells (Tregs), each with specific functions in immune regulation and defense against pathogens.
-T cells in the gut mucosa are exposed to a diverse array of antigens derived from commensal bacteria, food particles, and potential pathogens.
-Upon activation by antigen-presenting cells, such as dendritic cells, T cells undergo clonal expansion and differentiation into effector cells, which mediate immune responses tailored to the specific antigen encountered.
-T cells play critical roles in maintaining immune homeostasis in the gut, regulating inflammatory responses, and promoting tolerance to harmless antigens.
Which T cells are the most predominant in the small intestine?
TH17
State the functions of t cells in the gut.
- Immune Surveillance: T cells continuously survey the gut mucosa for the presence of pathogens, infected cells, and other abnormalities. This surveillance helps to detect and eliminate invading pathogens, preventing infections and maintaining gut health.
- Response to Pathogens: Upon encountering pathogens, T cells initiate immune responses to eliminate the invaders. CD4+ T helper cells differentiate into subsets such as Th1, Th2, and Th17 cells, which produce cytokines to activate immune cells like macrophages and recruit other immune cells to the site of infection.
CD8+ cytotoxic T cells directly kill infected cells to prevent the spread of pathogens.
- Regulation of Inflammation: T cells, particularly regulatory T cells (Tregs), help to control inflammation in the gut and prevent excessive immune responses. Tregs suppress the activity of other immune cells, such as effector T cells and dendritic cells, thereby maintaining immune tolerance to harmless antigens and preventing autoimmune reactions.
- Tissue Repair and Homeostasis: T cells contribute to tissue repair and maintenance of gut homeostasis. They produce growth factors and cytokines that promote the proliferation and differentiation of epithelial cells, aiding in the repair of damaged mucosal tissues.
- Immunological Memory: T cells in the gut can develop memory responses upon encountering pathogens. Memory T cells, formed after initial exposure to a pathogen, provide rapid and enhanced immune responses upon re-encounter with the same pathogen, leading to more effective clearance of the infection.
- Interaction with Microbiota: T cells interact with the gut microbiota, the diverse community of microorganisms residing in the gastrointestinal tract. They help to maintain a symbiotic relationship with commensal bacteria, promoting immune tolerance to beneficial microbes while responding to pathogenic bacteria.
- Mucosal Immunity: T cells contribute to mucosal immunity in the gut, particularly by producing immunoglobulin A (IgA) antibodies. IgA antibodies secreted by activated T cells help to neutralize pathogens and toxins in the gut lumen, preventing their invasion and maintaining intestinal barrier function.
Discuss the adaptive immunity of the gut.
- B cells
B Cells:
B lymphocytes, or B cells, are another key component of adaptive immunity responsible for antibody production.
B cells in the gut mucosa are stimulated by antigens encountered in the gut lumen or presented by antigen-presenting cells.
Upon activation, B cells differentiate into plasma cells, which secrete antibodies specific to the encountered antigens.
Immunoglobulin A (IgA) antibodies are particularly abundant in the gut mucosa and play a crucial role in mucosal immunity.
IgA antibodies produced by gut-associated B cells are transported across the epithelium and secreted into the gut lumen, where they neutralize pathogens, toxins, and harmful antigens, thereby preventing their entry into the body.
- What is class switching?
- Discuss
Class switching, also known as isotype switching or class switch recombination (CSR), is a process that occurs in B cells during their maturation and differentiation.
It involves changing the class of immunoglobulin (antibody) produced by the B cell, while retaining the specificity for the antigen recognized by its B cell receptor (BCR).
During class switching, B cells switch from expressing one class of antibody (typically IgM or IgD) to expressing another class, such as IgG, IgA, or IgE.
This process allows B cells to tailor the antibody response to different types of pathogens and immune challenges encountered in the body.
The process of class switching occurs in the germinal centers of secondary lymphoid organs (such as lymph nodes and spleen) and is mediated by specific enzymes, particularly activation-induced cytidine deaminase (AID).
What is T-dependent activation?
T-dependent activation refers to the process by which B cells are activated with the assistance of helper T cells (CD4+ T cells).
This pathway is crucial for the generation of robust and long-lasting antibody responses against protein antigens.
- Antigen Recognition: T-dependent activation begins with the recognition of protein antigens by B cell receptors (BCRs) on the surface of B cells.
Protein antigens are typically processed and presented by antigen-presenting cells (APCs), such as dendritic cells or macrophages, to helper T cells via major histocompatibility complex class II (MHC-II) molecules.
- Interaction with Helper T Cells: Upon encountering the antigen-MHC-II complex, naive helper T cells become activated.
This activation is facilitated by co-stimulatory signals, such as interaction between CD40 ligand (CD40L) on the T cell and CD40 on the B cell, as well as cytokines secreted by the activated T cell, such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-21 (IL-21).
- T Cell Help for B Cell Activation: Activated helper T cells provide critical signals that promote B cell activation and differentiation.
These signals include cytokines that regulate B cell proliferation, differentiation, and class switching. For example,
*IL-4 induces class switching to IgE or IgG1, while
*IL-5 promotes eosinophil activation and differentiation.
- Germinal Center Reaction: Following interaction with helper T cells, activated B cells migrate to the germinal centers of secondary lymphoid organs (such as lymph nodes and spleen).
Within germinal centers, B cells undergo clonal expansion, somatic hypermutation, and affinity maturation. This process results in the generation of B cell clones with increased affinity for the antigen.
- Differentiation into Memory B Cells and Plasma Cells: Some of the activated B cells differentiate into memory B cells, which provide long-lasting immunity upon re-exposure to the antigen.
- Others differentiate into plasma cells, which produce and secrete large quantities of antibodies specific to the antigen encountered. These antibodies contribute to the elimination of pathogens and provide immune protection.
