L9 - Immunology of the gut mucosa 1 - Dr Jamie Mann Flashcards
- Understand and define the concept of immune tolerance, particularly in the context of the immune system's response to food antigens. - Explain the basic components and functions of the mucosal immune system, including the mucosal structure and relevant immune cells.
What is the primary function of the mucosal immune system?
The mucosal immune system protects internal epithelial surfaces (e.g., gastrointestinal, respiratory, and urogenital tracts) from infection by pathogens such as bacteria, viruses, fungi, and parasites.
Which anatomical sites are considered part of the mucosal immune system?
The gastrointestinal tract, respiratory tract, urogenital tract, associated lymph nodes, and mammary glands.
Why is the mucosal immune system crucial for survival?
These surfaces are constantly exposed to pathogens. Without an effective mucosal immune response, harmful microbes could establish infections, replicate, and spread throughout the body.
How does the skin compare to mucosal surfaces in immune protection?
The skin is a strong physical barrier preventing pathogen entry. In contrast, mucosal surfaces are more vulnerable as they are exposed to external environments and require specialized immune protection.
What is the historical evolutionary link between mammalian skin and mucosal surfaces?
Millions of years ago, mammalian skin was originally mucosal tissue that secreted mucus. This adaptation was crucial for early marine organisms in protecting against pathogens in the ocean.
What is the role of mucus in immune defense?
Mucus acts as a physical barrier, trapping pathogens and preventing them from reaching epithelial cells. It also contains antimicrobial molecules that neutralize threats.
How do hagfish use mucus as a defense mechanism?
Hagfish secrete large amounts of mucus when threatened. This mucus clogs the gills of predators, effectively suffocating them and preventing predation.
What challenges do mucosal sites in the respiratory tract protect us from
- Particulates
- Pollutants
- Allergens
- Airborne pathogens
What challenges do mucosal sites in the gastrointestinal tract protect us from
- Food
- Commensals
- Ingested pathogens
What challenges do mucosal sites in the urogenital tract protect us from
Introduced pathogens
- Commensals
- Sperm `
What are the key functions of the mucosal immune system beyond pathogen defense?
It selectively responds to harmful pathogens but tolerates commensals, food antigens, and sperm to prevent unnecessary immune activation and inflammation.
How does the mucosal immune system regulate commensal microbes?
It maintains a symbiotic relationship with commensals, allowing them to exist without triggering inflammation, while still being capable of responding to pathogenic microbes.
Do food proteins always get broken down into amino acids before absorption?
No, while most dietary proteins are broken into amino acids, small amounts of intact proteins can enter the bloodstream.
Why doesn’t the immune system usually attack dietary proteins?
The mucosal immune system induces oral tolerance, a process that prevents an immune response against harmless food antigens, reducing the risk of food allergies.
What happens when oral tolerance fails?
Failure in oral tolerance can lead to food allergies, where the immune system mistakenly recognizes food proteins as harmful and triggers an inappropriate immune response (e.g., peanut allergy).
What do nutritionists and physiologists typically say about dietary protein absorption? ( and what is the however)
They often state that dietary proteins are fully broken down into polypeptides, then amino acids, which are absorbed by the gastrointestinal tract—meaning no intact proteins enter the bloodstream.
🔹 However, this is not entirely true!
✅ Small amounts of intact dietary proteins can cross the gut barrier and enter the bloodstream, but in most people, they do not trigger an immune response due to oral tolerance mechanisms.
What key experiment demonstrates oral tolerance?
Mice are fed an antigen (ovalbumin, OVA) and later immunized with the same antigen.
🔹 Group 1 (fed OVA) → Weakened immune response to OVA after immunization.
🔹 Group 2 (not fed OVA, control) → Strong immune response after immunization.
Step-by-Step Breakdown of the oral tolerance mouse experiment :
1️⃣ Feeding Phase (Day 0):
Experimental Group: Mice are fed ovalbumin (OVA), a model antigen.
Control Group: Mice receive a control solution (PBS) instead of OVA.
2️⃣ Immunization Phase (~Day 14):
All mice are injected with OVA + adjuvant to induce an immune response.
The adjuvant enhances immune activation, mimicking a real infection.
3️⃣ Measurement of Immune Response:
Researchers assess T-cell-mediated immunity using a delayed-type hypersensitivity (DTH) test (footpad swelling).
Serum antibody levels (IgA) are measured to evaluate humoral immune responses.
What does this experiment prove?
Prior exposure to an antigen via the gut can induce immune tolerance, preventing a strong immune response upon later exposure.
What happens if an animal is fed one antigen but immunized with a different antigen?
The immune system still responds to the new antigen, meaning tolerance is antigen-specific.
What immune responses are measured in this experiment
- T-cell response (delayed-type hypersensitivity, through a footpad swelling test)
- Serum antibody levels
Why does prior feeding of an antigen reduce immune responses?
The mucosal immune system actively suppresses immune responses to prevent unnecessary inflammation against harmless food proteins.
What was the purpose of the mouse tolerance induction experiment?
To demonstrate that prior oral exposure to an antigen (OVA) reduces the immune response upon later systemic immunization.
Why were different strains of mice (CBA, C3H, A) used in the study?
To show that oral tolerance is not strain-specific and occurs across different genetic backgrounds.
What were the two groups of mice in the tolerance induction experiment?
🔹PBS-fed group (control): Received sham feeding (PBS) before immunization.
🔹 OVA-fed group (experimental): Fed ovalbumin (OVA) before immunization.
What was measured after immunization in the tolerance induction experiment?
Serum anti-OVA antibody titers to assess the strength of the immune response.
What were the key results of the tolerance induction experiment?
🔹PBS-fed mice: High anti-OVA antibody levels (strong immune response).
🔹 OVA-fed mice: Lower anti-OVA antibody levels (indicating tolerance induction).
🔹 All three mouse strains showed oral tolerance, but with variation in response levels.
What does this tolerance induction experiment prove about oral tolerance?
Oral exposure to an antigen before systemic exposure can suppress the immune response, preventing excessive immune activation.
How does this tolerance induction experiment relate to food allergies?
Failures in oral tolerance mechanisms may contribute to food allergies, where the immune system incorrectly mounts a response to dietary antigens.
Is oral tolerance only observed in mice?
No, it has been observed in other species, including pigs, where prior feeding of an antigen (e.g., soya protein) leads to a reduced antibody response upon later immunization.
What experiment demonstrated oral tolerance in pigs?
Pigs were fed soya protein (soya based diets at 3 weeks old) before being immunized with soya protein -
🔹 PBS-fed pigs (control) → Developed a strong anti-soya antibody response.
🔹 Soya-fed pigs → Showed a reduced immune response, indicating tolerance induction.
Study: Weaning Piglets onto Soya-Based Diets at 3 Weeks Old
✅ What were the key findings and what does this indicate ?
1️⃣ Antibody responses were generated to food antigens (soya) after initial (prime) feeding.
2️⃣ Antibody response at weaning (green) was comparable to an injected protein antigen.
3️⃣ The antibody response in the weaning group was not boosted upon re-exposure, unlike the naïve or injected groups.
🔹 Oral exposure to soya at weaning induces a regulated immune response.
🔹 Oral tolerance mechanisms prevent excessive immune activation upon re-exposure
How does the historical example of Mithridates relate to oral tolerance?
Mithridates of Pontus (100 BC) reportedly consumed small doses of poison daily to build resistance.
🔹 While not true oral tolerance, this concept resembles the principle of gradual immune adaptation to antigens.
Why is the historical example relevant to immunology?
It illustrates early human attempts to induce tolerance, similar to how the immune system adapts to harmless dietary antigens.
What is the mucosal immune system vs the systemic immune system
the mucosal immune system is a specialised branch of the immune system that protects mucosal surfaces exposed to the external environment whilst the systemic immune system involves a network of organ tissues and cells that protect internal, non mucosal tissues from pathogens
Which antibody plays a dominant role in mucosal immunity, and what is its function?
Secretory IgA (sIgA) provides the first line of defense by neutralizing pathogens and toxins while preventing an overactive immune response to harmless antigens.
what does systemic immunity rely on
IgG, circulating immune cells, cytokines and antibodies : primarily IgG to detect and eliminate infections throughout the body’s internal compartments
List three key differences between mucosal and systemic immunity.
1️⃣ Mucosal immunity protects barrier surfaces, while systemic immunity protects internal organs and tissues.
2️⃣ Secretory IgA (sIgA) dominates mucosal immunity, whereas IgG dominates systemic immunity.
3️⃣ Mucosal immunity is tolerogenic to non-harmful antigens (e.g., food, commensals), whereas systemic immunity responds aggressively to eliminate pathogens.
which organs, tissues and cells make up the systemic immune system
primary lymphoid organs like bone marrow and the thymus and secondary lymphoid organs such as the sleen and peripheral lymph nodes
what is the lactating breast considered to be a part of
the mucosal immune system
besides the gastrointestinal, respiratory and urogential ( as well as lactating breast) what other parts of the body are considered to be apart of the mucosal immune system?
The oral cavity, pharynx, middle ear, and the glands associated with these tissues, such as the salivary glands and lacrimal glands.
What are the four main types of barriers in the mucosal immune system?
Physical, chemical, innate immune cell and microbial barriers that work together to protect mucosal surfaces from infections.
What makes up the mucus layer ( physical barrier - innate immunity) and what is their function
glycoporteins aka mucins which form a gel-like layer that traps pathogens, prevents adhesion, and facilitates their removal.
What is the function of epithelial tight junctions in mucosal immunity ( physical barrier - innate immunity)
They form a physical seal between epithelial cells, preventing microbial entry into tissues.
What is the function of cilia in the respiratory tract (physical barrier - innate immunity) ?
Cilia propel mucus and trapped microbes outward, preventing them from reaching the lungs.
How Does pH Act as a Chemical Barrier? (innate immunity)
The acidic environment of the stomach and vagina inhibits microbial growth, preventing infections.
Name Two Antimicrobial Peptides (AMPs) that act as chemical barriers in Mucosal Immunity (innate immunity)
Defensins and cathelicidins which disrupt microbial membranes, killing bacteria and viruses.
Defensins and cathelicidins ** (produced by, cationic nature and immune modulation) (innate immunity)
These peptides are primarily produced by epithelial cells lining various body surfaces like the skin, respiratory tract, gastrointestinal tract, and urogenital tract, creating a protective barrier at these entry points.
Cationic nature:
They are positively charged, which allows them to interact with the negatively charged bacterial membranes, disrupting their structure and leading to cell death.
Immune modulation:
Beyond direct antimicrobial activity, defensins and cathelicidins can also modulate the immune response by attracting immune cells to the site of infection and promoting wound healing.
What Is the Role of Lysozyme in Mucosal chemical Defense?
Lysozyme, found in tears, saliva, and mucus, breaks down bacterial cell walls, preventing infection.
What is the function of lactoferrin in mucosal chemical immunity? (innate immunity)
It sequesters iron, depriving bacteria of an essential nutrient and inhibiting their growth.
What are two ways that resident microbiota help prevent infections? (innate immunity)
1️⃣ Compete with pathogens for nutrients and attachment sites.
2️⃣ Produce metabolites (e.g., short-chain fatty acids) that enhance epithelial integrity.
What are four key innate immune cells involved in mucosal immunity?
1️⃣ Macrophages – Engulf pathogens and regulate inflammation.
2️⃣ Dendritic Cells – Sample antigens and initiate adaptive immune responses.
3️⃣ Neutrophils – Rapidly recruited to infection sites to clear pathogens.
4️⃣ Innat lymphoid cells (ILCs) - Early cytokine responses for immunity and tissue repair
What is MALT, and what is its role in mucosal immunity?
MALT (Mucosa-Associated Lymphoid Tissue) is a collection of immune tissues in mucosal surfaces that contain B cells, T cells, and antigen-presenting cells to help initiate immune responses and maintain tolerance.
What are the different subtypes of MALT based on location?
1️⃣ NALT – Nasal-Associated Lymphoid Tissue (upper respiratory tract) e.g. tonsils
2️⃣ BALT – Bronchial-Associated Lymphoid Tissue (lungs)
3️⃣ GALT – Gastrointestinal-Associated Lymphoid Tissue (intestines) e.g. peyers patches
( Mesenteric Lymph Nodes – Drain and support immune responses in the gut)
what are examples of regional lymph nodes
Retropharyngeal, submaxillary and parotid LN
Mediastinal LN
Mesenteric LN
What is a Peyer’s patch, and why is it important?
Peyer’s patches are large lymphoid aggregates found in the small intestine. They contain B cells and T cells and play a key role in initiating immune responses to gut antigens.
How does HIV affect mucosal immunity, particularly in the gut?
HIV depletes CD4 T cells, leading to destruction of lymphoid structures like Peyer’s patches, leaving the host vulnerable to infections.
What are isolated lymphoid follicles, and how do they differ from Peyer’s patches?
Isolated lymphoid follicles are smaller, dispersed lymphoid aggregates in the intestine that contain B and T cells, but they are generally smaller than Peyer’s patches. Exist in a range of sizes, with the larger displaying germinal center characteristics
What are cryptopatches, and how do they function in mucosal immunity?
Cryptopatches are tiny lymphoid aggregates in the gut that serve as sites for early immune cell development and may contribute to immune responses. Considered to develop into single B-cell follicles. Contain mainly innate lymphoid cells (ILCs) – see slide 14.
What Is the Role of Mesenteric Lymph Nodes in mucosal immunity ?
Mesenteric lymph nodes are large immune structures that help drain lymph from the intestines and coordinate immune responses to gut antigens.
What are the two main cells involved in the adaptive mucosal immunity
1️⃣T-cells
All the usual suspects – Th1, Th2, Th17, Treg
2️⃣B-cells
Lots of IgA plasma cells, some IgM, and some IgG secreting cells.
What Is Mucus?
Mucus is a gel-like secretion on mucosal surfaces made up of glycoproteins, water, lipids, and antimicrobial peptides. It is released by goblet cells. Its main function is to protect epithelial surfaces by trapping microbes and preventing direct contact with the epithelium.
What are goblet cells, and what do they secrete?
Goblet cells are specialized epithelial cells that secrete mucin glycoproteins, water, lipids, DNA, and antimicrobial peptides to maintain the mucus layer and protect mucosal surfaces.
How many types of mucin glycoproteins does the body produce?
The body produces 21 different types of mucin glycoproteins.
How does mucus act as a protective barrier in the gastrointestinal tract?
Mucus forms a physical barrier that prevents microbes from directly contacting epithelial cells. It also traps bacteria, preventing them from invading the gut lining.
What happens when the mucus barrier is compromised, such as in colitis
In conditions like colitis, the mucus layer becomes thinner, allowing bacteria to come into direct contact with the epithelial surface, leading to inflammation and damage.
Which antibody predominates in mucosal secretions, and which predominates in the systemic compartment?
IgA predominates in mucosal secretions, while IgG is the dominant antibody in the systemic (blood) compartment.
% proportion of immunoglobulins (IgM, IgG, IgD and IgA) in the systemic compartment
IgM = 17%
IgG = 52%
IgD = 1%
IgA = 30%
% proportion of immunoglobulins (IgM, IgG, IgD and IgA) in mucosal secretions
IgM = 13%
IgG = 6%
igD = 1%
IgA = 80%
How does IgA differ in the systemic compartment versus mucosal surfaces?
- Systemic IgA is mostly monomeric, with only 1-5% in polymeric form.
- Mucosal IgA is predominantly in their polymeric form, with a smaller fraction as monomeric IgA.
What are the key functions of IgA in mucosal immunity?
- Neutralization – Binds to pathogens and toxins to prevent infection.
- Secretion into the Lumen – Actively transported into mucosal secretions where -pathogens reside.
- Pathogen Removal – Can bind to invading pathogens inside the body and transport them back out via receptor-mediated translocation.
what are IgA antibodies produced in response to in mucosal tissues
IgA antibodies are produced in response to the specific commensal bacteria present in a particular mucosal environment. This selective response helps shape the composition of the microbiota and maintain a balanced relationship between the host and commensals.
what does IgA prevent
prevents commensal bacteria from entering mucosal tissues by binding to these microorganisms in the mucosal lumen.
how can IgA neutralise potential threats
IgA can neutralize potential threats by binding to surface structures or toxins of commensal bacteria
Why is IgA used as a marker for mucosal vaccine efficacy?
Since IgA is the primary mucosal antibody, its induction indicates a strong mucosal immune response, making it an important marker in mucosal vaccine development.
What are the major cytokines involved in the differentiation of naïve T cells (Th0) into specific T cell subsets (Th2, Th1, Th17 and Treg)
IL-4 → Th2
IL-12 → Th1
TGF-β & IL-6 → Th1`7
TGF-β → Treg
What is the role of Th1 cells in mucosal immunity?
Transcription factor: T-bet
Cytokines secreted: IFN-γ
Target: Intracellular pathogens (e.g., viruses, intracellular bacteria)
What is the function of Th2 cells?
Transcription factor: GATA-3
Cytokines secreted: IL-4, IL-5, IL-13
Target: Parasites (e.g., helminths)
What do Th17 cells do in mucosal immunity?
Transcription factor: RORγt
Cytokines secreted: IL-17A/F
Target: Extracellular bacteria (e.g., PMNs, neutrophils)
What is the function of regulatory T cells (Tregs)?
Transcription factor: FoxP3
Cytokines secreted: IL-10, TGF-β
Function: Suppress excessive immune responses to maintain tolerance
What are antimicrobial peptides, and how do they function?
small cationic peptides less than 100 aa in size produce by epithelial cells and immune cells e.g. Paneth cells in crypts. They play a crucial role in mucosal immunity by punching holes in pathogen membranes, leading to pathogen destruction
what are two examples of antimicrobial peptides
Defensins & Cathelicidins
Defensins :
Small cysteine-rich cationic peptides that disrupt microbial membranes and modulate immune responses, classified into α- and β-defensins based on structure and expression patterns. Produced by Paneth cells.
Cathelicidins
Linear antimicrobial peptides, exemplified by LL-37, that disrupt microbial membranes and regulate inflammation and immune signaling. Produced by enterocytes.
What is the function of M cells in mucosal immunity?
M cells, located in Peyer’s patches of the intestine, sample antigens from the external environment and transport them to immune cells like dendritic cells and T cells. This process is vital for initiating and modulating immune responses, helping the body recognize pathogens while maintaining tolerance to harmless substances.
How do M cells help transport antigens?
`The minimal gap between the M cell pocket and the external environment facilitates efficient transport of antigens, organisms, and proteins into the body. This process aids dendritic cells and T cells in recognizing pathogens and initiating immune responses.
How are M cells distinguished from neighbouring enterocytes in the FAE
M cells can be distinguished from neighboring enterocytes in the FAE by architectural features (short and blunted microvilli and an intraepithelial pocket housing mononuclear phagocytes and lymphocytes),
M cell structure
- Apical microfolds
These are poorly organized villi that lack the uniform microvilli of other intestinal epithelial cells. - Thin glycocalyx
This allows for adhesion but also allows molecules to pass through. - Intraepithelial pockets
These invaginations on the basolateral surface of M cells form pockets that harbor lymphocytes. - Basolateral membrane
This membrane is invaginated, forming pockets that reduce the distance antigens have to travel to reach the basolateral membrane.
What role do dendritic cells play in antigen sampling?
Professional antigen-presenting cells (APCs) extend dendritic arms between epithelial cells into the gut lumen to sample antigens. They detect foreign material and present it to T cells for immune activation.
What are CD11c+ dendritic cells, and what is their unique function?
CD11c+ dendritic cells are specialized immune cells that extend projections into the gut lumen to sample pathogens and antigens. Their unique function is to present these antigens to T cells, thereby initiating adaptive immune responses and maintaining immune balance in the gut.
where are CD11+ dendritic cells located
closly associated with epithelial cells in the gut lining
How do CD11c+ dendritic cells sample antigens in the gut?
Extend dendrites through junctions of epithelial cells. Directly capture bacteria and antigens from the lumen. This process aids in immune surveillance and the initiation of immune responses.
How are CD11c+ dendritic cells visualized in research studies?
Transgenic mice expressing GFP under the CD11c promoter demonstrate green fluorescence.
Fluorescent markers are as follows:
Green: CD11c+ dendritic cells
Red: Cytokeratin (an epithelial marker)
Blue: Nuclei
This shows dendritic cells extending dendrites between epithelial cells into the gut lumen.
Why is dendritic cell antigen sampling important for immune defense?
Captures pathogens & antigens from the gut lumen
Presents antigens to T cells to trigger adaptive immune responses
Helps maintain immune tolerance to commensal microbiota while defending against pathogens
What is immune tolerance?
A mechanism employed by the immune system to dampen immune responses against harmless antigens, such as food proteins or commensal bacteria.
What role do dendritic cells (DCs) play in immune tolerance?
DCs are antigen-presenting cells that sample the environment.
They are crucial in determining whether an immune response should be activated or suppressed to maintain tolerance.
How did researchers study the role of DCs in tolerance?
They depleted DCs in a mouse model using the CD11c-DTR system, where DCs express the diphtheria toxin receptor (DTR) and can be eliminated by diphtheria toxin.
What is the purpose of the CD11c-DTR system in immunological research?
The CD11c-DTR system allows researchers to selectively deplete dendritic cells (DCs) in mice by expressing the diphtheria toxin receptor (DTR) on DCs. When diphtheria toxin (DT) is administered, only DCs are eliminated, helping scientists study their role in immune responses and tolerance.
Why don’t normal mice get affected by diphtheria toxin?
Mice are naturally resistant to diphtheria toxin because they do not express the diphtheria toxin receptor (DTR).
How did researchers deplete DCs in their experiment?
They engineered transgenic mice to express the diphtheria toxin receptor (DTR) under the CD11c promoter (a marker for dendritic cells).
When diphtheria toxin (DT) was administered, it killed DCs via apoptosis.
What happens when dendritic cells are depleted?
No antigen presentation occurs, preventing T cell activation, and no immune response is generated.
What are OT-I and OT-II mice, and how do they help in T cell research?
These mice have T cells engineered to recognize a specific OVA (Ovalbumin) peptide.
OT-I mice: Have CD8+ T cells recognizing OVA via MHC Class I (H-2Kb).
OT-II mice: Have CD4+ T cells recognizing OVA via MHC Class II (I-Ab).
Used to study cytotoxic (CD8+) vs. helper (CD4+) T cell responses.
What happens when OT-II T cells are transferred into CD11c-DTR mice?
If DCs are present: OT-II T cells proliferate upon encountering OVA.
If DCs are depleted (DT treatment): No proliferation occurs.
How was T cell proliferation assessed?
Using CFSE staining, which allows tracking of T cell division.
Proliferating cells lose CFSE intensity over time as the dye gets diluted.
What do the CFSE flow cytometry graphs in Peyer’s Patch (PP) and Mesenteric Lymph Node (MLN) show?
- Without DT (-DTx):
20% of OT-II T cells proliferate in Peyer’s Patch.
49% of OT-II T cells proliferate in the Mesenteric Lymph Node. - With DT (+DTx) (DC depletion):
Only 3% of OT-II T cells proliferate (significantly reduced)
What conclusion can be drawn from the CFSE proliferation data?
- Dendritic cells (DCs) are essential for priming naïve CD4+ T cells after mucosal immunization with OVA.
- Without DCs, T cells fail to proliferate, showing that DCs are crucial for initiating immune responses.
Why is the response in the Mesenteric Lymph Node (MLN) stronger than in Peyer’s Patch (PP)?
The MLN is a major site for antigen presentation, leading to higher T cell activation.
The MLN is a major site for antigen presentation, leading to higher T cell activation.
It demonstrates that conventional dendritic cells (cDCs) are critical for mucosal immune responses.
Deleting CD11c+ DCs prevents immune activation, which is crucial for understanding tolerance mechanisms.
What are the major subsets of CD11c+ dendritic cells (DCs) involved in immune responses?
CD103+ DCs – Found in mucosal tissues, responsible for activating T cells and inducing gut-homing properties.
CX3CR1+ DCs – More associated with maintaining immune homeostasis and tolerance rather than activating T cells.
(CD11c: general marker)
Which dendritic cell population is responsible for triggering T cell proliferation?
CD103+ CD11c+ dendritic cells are responsible for T cell activation and proliferation. These DCs uptake antigens, migrate to mesenteric lymph nodes (MLN) or Peyer’s patches, and activate naïve T cells.
What molecules are essential for gut-homing of T cells, and how are they induced?
- CCR9 – Binds to CCL25, guiding T cells to the gut.
- α4β7 integrin – Binds to MAdCAM-1, which is expressed in gut vasculature.
- These molecules are upregulated by mucosal DCs but not by blood-derived DCs
How do blood-derived and mucosal dendritic cells differ in T cell activation?
- Mucosal DCs induce gut-homing markers (CCR9, α4β7) on T cells, directing them to mucosal tissues.
- Blood-derived DCs can activate T cells but do not induce gut-homing properties, meaning those T cells will not migrate to the gut.
Why is the ability of dendritic cells to program T cell homing important for vaccine development?
To protect mucosal surfaces (e.g., gastrointestinal or respiratory tract), vaccines must stimulate mucosal DCs to ensure that T cells acquire the correct homing markers (CCR9, α4β7) and migrate to the appropriate site. Using blood-derived DCs may activate T cells but not direct them to mucosal tissues.
What molecules are involved in lymphocyte homing to mucosal tissues?
Lymphocytes express Alpha4Beta7 and CCR9, while endothelial cells express MAdCAM-1 and CCL25. These interactions help lymphocytes locate the correct vasculature and enter tissues.
What is the main mechanism behind oral tolerance?
Induction of regulatory T cells (Tregs), not deletion or anergy.
How does CCL25 guide lymphocytes?
CCL25 creates a gradient that lymphocytes follow, allowing them to home to specific tissues
How do Tregs contribute to oral tolerance?
Tregs suppress immune responses and prevent inflammation in the intestines by producing immunosuppressive cytokines like IL-10.
What happens when CD4 T cells are introduced into SCID mice?
The mice develop colitis due to T cell activation by dendritic cells, leading to inflammation in the intestines.
What did researchers discover about IL-10 producing Tregs in SCID mice?
When SCID mice were fed OVA, IL-10 producing Tregs proliferated and prevented colitis, demonstrating that Tregs protect against inflammation.
What role do CD103+ dendritic cells play in Treg activation?
They are crucial for activating FoxP3+ Tregs, which suppress immune responses.
How do researchers identify Tregs?
By their high FoxP3 expression, which is a hallmark of regulatory T cells.
What happens if Tregs are deleted in mice?
Severe inflammation occurs, proving Tregs are essential for immune regulation.
How do Treg populations change after antigen exposure?
They expand significantly over days, reaching up to 56% by later stages.
How can understanding oral tolerance help in medicine?
It can be applied to vaccines, autoimmunity, food allergies, and intolerances.
What molecules help lymphocytes home to mucosal tissues?
Lymphocytes express Alpha4Beta7 integrin and CCR9, which bind to MAdCAM-1 and CCL25 on endothelial cells to facilitate tissue entry.
How does CCL25 guide lymphocyte migration?
CCL25 forms a gradient that lymphocytes follow, helping them locate and enter the correct tissue.
What happens when MAdCAM-1 binds to Alpha4Beta7?
The interaction helps anchor lymphocytes to the vasculature, allowing them to exit blood vessels into tissues.
How do Tregs contribute to immune regulation?
Tregs suppress immune responses by secreting IL-10, which prevents excessive inflammation.
What is a SCID mouse, and why is it used in immune studies?
A SCID (Severe Combined Immunodeficiency) mouse lacks T cells, B cells, and NK cells, making it highly susceptible to infections. It is used to study immune cell interactions.
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