L25 - Mucosal Immune Responses Flashcards
How does the intestinal immune system protect the gut while maintaining tolerance?
The gut secretes a mucus layer that keeps microbes physically separated from the epithelium. Beneath this layer, a network of immune cells maintains tolerance to harmless antigens like food and commensals. Antigens from the gut are transported to nearby lymph nodes, where they activate T and B cells, initiating adaptive immune responses when needed.
How do you stop T and B cells responding to food?
- Food is full of Ags.
•Central tolerance can delete self-reactive T cells, but can’t delete T cell recognising foreign (non-self) non-dangerous antigens.
•Everyone has T cells that recognise food Ag.
Food: take up food antigens presented to T cells but bc they don’t have PPR (signal 1 but no signal 2 so T cell dies and deactivates, anergy)
What are the 2 signals required for T cell activation
MHC -Ag interacts w T cell receptor (signal 1)
Danger signal (signal 2)
How is the danger signal perceived
Danger signals (PAMPs) up-regulate B7 (CD80/86) on APC
•B7 signals to the T cell via CD28
The presence of B7 on the APC tells the T cell that the Ag it is recognising comes from a microbe and it should respond.
What is oral tolerance, and how does it differ from an oral vaccine response?
Oral tolerance occurs when soluble antigens are taken in through the gut, leading to immune tolerance—minimal T cell response due to lack of co-stimulatory signals (no signal 2). In contrast, oral vaccines include adjuvants that provide signal 2, triggering a strong T cell response. Tolerance creates memory to not respond to harmless antigens, while vaccination builds effector memory to mount a stronger response upon re-exposure.
How does oral tolerance prevent immune responses to harmless antigens like food?
- Delete T cells that recognise peanut → anergy
- Specific subsets of T cells: T cells become inert
- Induce inhibitory cytokine → opposite of pro, turns of T cells and B cells
- Treg → inhibitory T cell rather than promote
What happens when oral tolerance fails, and how does it differ between celiac disease and food allergies?
In celiac disease, gluten triggers a Th1-dominated response with increased IFN-γ, activating macrophages and plasma cells.
In food allergies (e.g., peanuts), allergens induce a Th2 response, leading to increased IL-4 and promoting IgE production—driving allergic inflammation.
What is the predominant antibody response in intestines and why?
•IgA’s dimeric structure makes it very good at clumping together and neutralising pathogens. The dimer binds to polyIC receptor to prevent it from digestion
•Peyers Patch B cells have higher rates of somatic hypermutation making IgA higher affinity and better at neutralising pathogens
•IgA is poor at stimulating ADCC so does not activate strong inflammatory responses that could impair the epithelial barrier
What are some ways of passive approach by mucosal immunity
- Tight junctions – prevent epithelium penetration
•Mucus layer – prevents microbes getting to epithelium
•Anti-microbial peptides – in inner mucus layer. Damage microbes that get too close to epithelium.
•IgA – Specialised for neutralising and blocking microbes.
Why are commensals good for us
- detoxify harmful molecules
- Biosynthetic → makes vitamin K
- Metabolic - breaks down fibres we can’t digest
- Protective - exclude pathogens
- Help promote more mature immune response
- No comensal = stunted immune response
- Commensals regulate immune response
How do commensals protect? What is he result if they are destroyed?
By filling up intestinal niche
- Strong antibiotic → leaves big space bc commensals are killed
- Neutrophils come in and there is a pathology bc walls are broken and harsh inflammatory
How can commensals still be dangerous
- They will mount opportunistic infections
- They have lower virulence
- It does detect commensals (PAMPs)
How does appendicitis arise?
- Appendix gets blocked
•Build up of mucus and intestinal/microbial products
•Immune inflammation occurs dropping barrier integrity
•Commensals invade lamina propria via epithelium
•Increased inflammatory response
•Appendix burst leading to peritonitis
•Life threatening – friendly bacteria no longer quite so friendly (opportunistic pathogens).
What are IBDs
- lost structure in the gut
- Linked to overenthusiastic commensals
How is IBD associated with over zealous responses against commensals
- barrier goes wrong
- We lose mucus
- Gets into lining and affect gut
- Causes gut damage (IgG IFNy TNFa)
- Causing collateral damage
What are some evidence to show that microbes train the immune system how to respond
- as yo9u get older»_space;> microbial diversity
- Giving young babies antibodies that kills commensals may induce allergic diseases
- Important in setting your immune set point
- Kids growing up on farms have less allergies (kids are exposed to farm dust all the time), LPS is dangerous which is in the farm dusts but small exposures early life trains your immune response
