Immunological Functions of the Alimentary Tract Flashcards
(16 cards)
Compare innate and adaptive immunity
Innate:
- Prevents infection and avoids disease
- Non-specific, no memory
- Mediated by macrophages, epithelial barriers, secretions etc
Adaptive:
- Responds to infection and prevents disease
- Highly specific response to targeted microbe
- Memory
- Mediated by - Lymphocytes, antibodies
What is systemic immunity?
Immunity mediators within bone marrow, spleen, thymus, lymph system, blood circulation
What is mucosal immunity?
Immunity mediators within mucous membranes - eyes, nose, mouth, lungs, gut, GU tract
Describe the features and mechanisms of the mucosal immune system
- Mucosal surfaces - Oral, nasal, lacrimal surfaces, GI tract, bronchial tract, GU tract, mammary glands
- All sites non-sterile and colonised by microbes
- Main route of entry for infectious microorganisms
- Large SA specialised for absorption
Innate mechanism includes:
- Mucin, peristalsis, antimicrobial peptides and proteins e.g. lysozyme, lactoferrin; phagocytes
Adaptive mechanism includes:
- Mucosal/secretory immune system
Must be able to discriminate b/w harmful pathogens and harmless antigens - foods and commensal bacteria
Describe the features of the mucosal barrier
Innate:
- Natural barriers (e.g. stomach)
- Mucin
- Peristalsis
- Proteolysis
- Microvillus membrane or squamous cell
Immunological:
- Secretory IgA/IgM/IgG
What are sources of serum, saliva and local antibodies in the oral cavity?
- Lymphoid tissue
- Peripheral blood
- Gingival focus of leucocytes
- Salivary gland
- Crevicular fluid
- Saliva
What are the lymphoid cells of the gut?
- Intra-epithelial lymphocytes
- Lymphocytes and macrophages scattered in lamina propria
- Peyer’s patches (along jejenum and ileum, increase proximal to distal)
Explain how Peyer’s patches function as lymphoid tissues
- Peyer’s patches have unique epithelium containing M cells. Specialised for transporting antigens from intestinal lumen to underlying lymphoid tissue.
- M cells actively engulf pathogens via phagocytosis
- Via transcytosis, they transport the antigens across the epithelium from apical surface to basolateral surface
Describe the predominant muscosal antibody
- Predominantly SIgA
- Found in all secretions and breast milk
- Provide passive immune protection in new-born infants
Describe the mechanism of action of antibodies
- Binding to key functional sites on microbes and toxins
- Agglutination - Antibodies bind to antigens on cells, causing them to clump together, helps neutralise pathogens and prevent them from infecting cells.
- Induce inflammation
- Recruit immune cells
Where is the muscosal immune system usually stimulated?
- Site of stimulation usually at specialised sites in GALT, BALT and NALT
Gut-associated lymphoid tissue (GALT) isa collection of lymphoid tissues located throughout the gastrointestinal tract
NALT = Upper resp tract lymphoid tissue
BALT = Bronchal lymphoid tissue
Describe the features of secretory antibodies, how do they vary from serum antibodies
E.g. SIgA
- Dimeric/polymeric structure - Secretory antibodies often consist of multiple Y-shaped subunits (IgA) monomers linked by J chain, forming dimeric structure. Allows them to bind multiple antigens simultaneously, strengthening the interaction. 2 antibodies dimerise via
- J chain - Helps stable polymeric structure by linking individual IgA monomers
- Produced by mucosal epithelial cells, protects antibody from degradation in harsh muscosal environment/presence of proteolytic enzymes. Facilitates antibody’s transport across epithelial barrier, enhances its binding to pathogens
- Found in muscosal secretions i.e. tears, saliva, breast milk, mucus in GI and resp tracts
Dimeric structure allows for binding of 4 pathogens instead of 2, meaning it’s harder for pathogens to burrow in the mucosal surface.
What are some approaches to oral immunisation?
- Attenuated virus (e.g. polio)
- Attenuated recombinant bacterialk mutants (e.g. salmonella typhi)
- Mucosal adjuvants (e.g. cholera toxin)
- Liposomes, microspheres
- Capsules
- Transgenic edible plants
Describe oral vaccine delivery using GM plants
- Hep B surface antigen gene, is transferred from yeast into a plant cell cell (potato is used as a prototype)
- Potato plants regenerated from transformed cells
- Hepatitis vaccine is correctly expressed by potato plants
- GM potatoes are harvested that contain the hepatitis vaccine
Explain the concept of oral tolerance
- Orally delivered antigens can suppress systemic immunity -natural mechanism to prevent immune reactions to food and useful commensals. Allows GI tract to distinguish b/w commensals and pathogens
- If an antigen is first encountered through the mucosal immune system, the systemic immune system may become unresponsive (tolerised- turns off B/T cells) to that antigen. Food can act as antigen.
- Practical Considerations of Oral Tolerance:
- Tolerance to dietary foods, breakdown to food allergy
- Oral vaccination and safety
- Treatment and prevention of autoimmune diseases
Discuss oral tolerance being a contra-indication for oral immunisation
Oral tolerance, where the immune system is desensitized to antigens introduced orally, can be a contraindication for oral immunization because it can prevent the desired immune response to the vaccine. Oral tolerance can lead to suppression of the immune response, including anergy (unresponsiveness) and deletion of specific T cells. This can hinder the vaccine’s ability to stimulate the immune system and develop protective immunity.
Induction of oral tolerance can depend on many factors, such as nautre of antigen, dose, frequency of delivery
- Tolerance: Soluble antigens; Vaccinaion: Antigen/adjuvant or other formulations
- Tolerance: Repeated sustained doses; Vaccination: Limited number of immunisations
- Tolerance: High doses (e.g. 20-500mg bolus); Vaccination: Low dose (usually in microgram range)
