immunological functions of the alimentary tract Flashcards
what is the mucosal immune system ?
- Mucosal surfaces: oral, nasal, lacrimal surfaces gastrointestinal tract, bronchial tract, Genito-urinary tract and mammary glands
- All sites are non- sterile as they are exposed to the environment and colonised by microbes
- Main route of entry for infectious microorganisms
- Large surface area specialised for absorption. Gut ~ 200m2 Skin ~2m2
what are the innate and adaptive mechanisms in the mucosal immune system ?
- Innate mechanisms of protection include: mucin, peristalsis, antimicrobial peptides and proteins e.g. lysozyme, lactoferrin; phagocytes
- Adaptive mechanisms are also present: mucosal/secretory immune system
- Must discriminate between harmful pathogens and harmless antigens – foods and commensal bacteria
what comprises of the mucosal barrier ?
Innate: Natural barriers
* (eg stomach)
* Mucin
* Peristalsis
* Proteolysis
* Microvillus membrane or squamous cell
Immunological: Secretory IgA/IgM
IgG
what are the sources of serum , saliva and local antibodies in the oral cavity ? - ( may not be asked but just in case)
- Lymphoid Tissue – A source of immune cells that contribute to systemic immunity.
- Peripheral Blood – Carries immune cells and antibodies to different parts of the body, including the oral cavity.
- Gingival Focus of Leukocytes – White blood cells accumulate in the gum tissue to help fight infections.
- Salivary Gland – Produces saliva, which contains antibodies (like IgA) that help protect the oral environment.
- Crevicular Fluid and Leukocytes – This fluid, found in the crevicular domain (the small gap between the teeth and gums), contains immune cells and proteins that contribute to local defense.
- Saliva – A major source of antimicrobial proteins and antibodies that help protect teeth and soft tissues.
what are the lymphoid cells in the gut ?
- intra-epithelial lymphocytes
- lymphocytes and macrophages scattered in lamina propria
- peyers patches
what is a peyers patch ?
- specialised lymphoid tissue found in small intestine - ileum
Functions:
* immune Surveillance – Detects harmful bacteria and viruses in the gut.
* Antibody Production – Contains B cells, which produce IgA antibodies to neutralize pathogens.
* T Cell Activation – Helps activate T cells, which play a role in adaptive immunity.
* Microbial Balance – Maintains a healthy balance of gut bacteria and prevents harmful infections
structure:
* M cells (Microfold cells): Specialized cells that sample antigens (foreign substances) from the intestine.
* B and T Lymphocytes: Immune cells that help mount a defense against infections.
* Follicles: Contain clusters of immune cells for rapid response to pathogens.
how was the function of peyers patches determined ?
- Animal Models Used: Researchers conducted studies on mice, rabbits, and other animals to understand the role of Peyer’s patches in immunity.
- Scientists surgically removed Peyer’s patches or genetically modified animals to lack them.
- They then exposed these animals to intestinal infections or oral vaccines to observe immune responses.
- Animals without Peyer’s patches had a weaker immune response to gut infections.
- Their ability to produce IgA antibodies (which protect the gut) was significantly reduced.
- The balance of gut microbiota was disrupted, leading to increased infections.
- The ability of the gut to recognize and respond to antigens was impaired.
what are the functions of M cells ?
Antigen Sampling and Transport:
* M cells capture antigens (bacteria, viruses, toxins, food particles) from the intestinal lumen.
* They transfer these antigens to underlying dendritic cells, macrophages, and lymphocytes in Peyer’s patches.
Immune Activation:
* Once the antigens are delivered, dendritic cells present them to T cells.
* This process helps trigger an adaptive immune response, including the activation of B cells, which produce IgA antibodies to fight infections.
Oral Tolerance:
* M cells help the immune system distinguish between harmful pathogens and harmless substances like food and beneficial gut bacteria.
* This prevents unnecessary immune responses that could lead to allergies or inflammatory diseases.
Gateway for Oral Vaccines:
* Since M cells efficiently transport antigens to immune cells, they are targeted for oral vaccines (e.g., polio and cholera vaccines).
* This allows for mucosal immunity, which is crucial for protecting the gut from infections.
Role in Disease:
* Some pathogens, like Salmonella, Shigella, and prions, exploit M cells to enter the body and cause infections.
* These bacteria invade through M cells, avoiding normal gut defenses and leading to diseases like diarrhea and gastroenteritis.
describe the pathway of the common mucosal immune system
- Antigen Uptake in the Gut (Induction Site):
* The antigen (Ag) enters through the intestinal lumen and is captured by M cells in Peyer’s patches (part of the gut-associated lymphoid tissue, GALT).
* Dendritic cells (DCs) process the antigen and present it to T cells in the Peyer’s patches. - Activation of Immune Cells
* T cells become activated and help stimulate B cells to produce IgA antibodies (a key mucosal antibody).
* Activated B and T cells move to the mesenteric lymph nodes, where they further mature. - Migration Through the Thoracic Duct (Circulation Phase):
* The activated immune cells enter the lymphatic system and travel through the thoracic duct into the bloodstream.
* This allows them to reach distant mucosal tissues beyond the gut. - Homing to Mucosal Effector Sites (Response Sites):
* The immune cells selectively migrate to different mucosal effector sites, including:
* Salivary glands (oral cavity protection)
* Lacrimal glands (eye protection)
* Mammary glands (immunity in breast milk)
* Lungs (respiratory immunity)
* Genito-urinary tract (protection in reproductive and urinary systems)
* Plasma B cells in these sites produce IgA antibodies, which provide local immune protection.
compare and contrast serum IgG and secretory IgA
what are some approaches to oral immunisation ?
- Attenuated virus (eg polio)
- Attenuated recombinant bacterial mutants (eg Salmonella typhi)
- Mucosal adjuvants (eg cholera toxin)
- Liposomes, microspheres,
- Capsules
- Transgenic edible plants
describe oral vaccine delivery using GM plants
- The Hep B surface antigen gene, is transferred from yeast into a plant cell (potato is used as a prototype).
- Potato plants are regenerated from transformed cells
- Hepatitis vaccine is correctly expressed by potato plants
- GM potatoes are harvested that contain the hepatitis vaccine
Why Aren’t Mucosal Immunity Vaccines Used as Frequently as Systemic Immunity Vaccines?
Complexity of Mucosal Immunity:
* The mucosal immune system is different from the systemic immune system and is designed to be tolerant to harmless antigens (like food and gut microbiota).
* Generating a strong immune response at mucosal surfaces without triggering excessive inflammation is challenging.
* IgA responses are harder to induce than IgG responses, requiring special vaccine formulations.
Vaccine Stability and Delivery Challenges:
* Mucosal vaccines must survive harsh environments like stomach acid and digestive enzymes.
* Many protein-based vaccines degrade before they can stimulate an immune response.
* Some vaccines need adjuvants (immune-stimulating additives), but safe mucosal adjuvants are limited.
Lower and Shorter Immunity in Some Cases:
* Systemic vaccines (injections) often produce strong, long-lasting IgG responses, while mucosal vaccines * sometimes generate weaker or shorter-lived protection.
* Boosters may be required more frequently for mucosal vaccines.
Limited Success in Some Diseases:
* While mucosal vaccines work well for gut and respiratory diseases (e.g., polio, cholera, flu nasal spray), they have struggled with other infections.
* Many viruses and bacteria evade mucosal immunity, requiring a strong systemic response instead.
Easier Regulation and Production of Injectable Vaccines:
* Most current vaccine technologies (e.g., mRNA, protein subunits) are designed for intramuscular or subcutaneous injection.
* Manufacturing, storage, and distribution of systemic vaccines are well-established, making them easier to produce and regulate.
When Are Mucosal Vaccines Preferred?
* Despite these challenges, mucosal vaccines are preferred when:
✔ The infection enters through mucosal surfaces (e.g., polio, cholera, rotavirus, flu).
✔ Systemic vaccines fail to prevent transmission (e.g., intranasal COVID-19 vaccines are in development).
✔ Need for needle-free delivery (e.g., easier administration for mass vaccination).
what is oral tolerance ?
- an active process of local and systemic immune unresponsiveness to orally ingested antigens such as food.
- Orally delivered antigens can suppress systemic immunity
- If an antigen is first encountered through the mucosal immune system, the systemic immune system may become unresponsive (tolerised) to that antigen.
what are the practical considerations of oral tolerance ?
- Tolerance to dietary foods, breakdown to food allergy.
- Oral vaccination and safety
- Treatment and prevention of autoimmune diseases
is oral tolerance a contra indication of oral immunisation ?
- goal is to make your immune system react and fight off diseases. But the challenge is that if you give too many doses or too much of the same thing, your immune system might stop reacting to it, which would make the vaccine less effective.
- Induction of oral tolerance can depend on many factors, such as the nature of the antigen, dose and frequency of delivery.
- Tolerance: Soluble antigens
Vaccination: Antigen/adjuvant or other formulations - Tolerance: Repeated sustained doses
Vaccination: Limited number of immunisations - Tolerance: High doses (eg 20-500mg bolus)
Vaccination: Low dose (usually in mg range)
