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
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)
