Where are the mucosa found ?
Lungs, gut, eyes, nose, uterus etc
- Where most infection enters - needs to be semi-permeable as is constantly interacting with pathogens
How does the mucosa’s immune response work?
- Is a balance between an overt immune response and a tolerogenic response
What Is a MALT and give an example (2 points)
- Mucosa associated lymphoid tissue
- e.g., Peyers patches in gut - have high population of B-cells - interact with DCs - migrate to lymph node
- Then home back to where the infection was found - specific antigen
What allows the mucosa to respond very quickly to infection?
Because they do not need to be primed by Dendritic cells first
What does the mucosa use as its effectors?
IgA antibodies
Why will the mucosa not usually trigger an overt response? 1 point
Mucosal tissue contains a high abundance of tolerogenic cytokines e.g., TGF-beta
For each structure in the gut, what does stem cell differentiation create?
enterocytes - absorptive - AMPs production
Paneth cells - antimicrobial peptide production - AMPs
Goblet cells - mucus secretion
How is IgA excluded?
plgR - binds to IgA - and it is exocytosed into the gut lumen
What are IELs and what are the two types?
Intraepithelial Lymphocytes
Type 1: Similar to CD8 cells but are already primed - and have an activated phenotype
- can rapidly recognise abnormal phenotypes expressed by cells and eliminate epithelial cells in presence of infection
Type 2: Activated IELS- but don’t interact with MHC peptide complexes
- Interact with MHC like molecules on stress cells
How is celiacs disease caused?
Caused by overt/excessive activation of IELs
- HLA-DQ2 - binds gliadin - lymphocyte mediated
What are ILCs?
Innate lymphoid cells - counterpart of CD4+ T helper cells
- Secrete cytokines that respond quickly to pathogenic tissue damage
What are ILCs equivalents to in helper cells?
Group 1 ILCs - Th1 cells
Group 2 ILCs - Th2 - secrete IL-4/5/9/13 - activate eosinophils + wound repair - skew B cell development
Group 3 ILCs - Th17/Th22 - defensives - mucus - antic peptides - are ready to secrete cytokines and skew/enhance immune response
Function of DCs
- Constantly sampling antigens from environment and presenting them to T cells
- Trigger T cells - CD4+ and CD8 cytotoxic
- T and B cell maturation
How are tolerogenic DCs different?
- Secrete anti-inflammatory - T regs - CD103+
- Imprint homing and upregulate - so T and B cells just continue circulating and are not matured
How does the mucosa interact with commensal bacteria?
- Interact in happy equilibrium
- Extract and synthesise metabolites
- They compete with unwanted pathogens - inhibit pathway required for pathogen uptake
- Small reactions - tolerogenic - low level inflammatory response - don’t want big response as it would kill them all
- Commensals actively down regulate the inflammatory pathway
What is down regulated in the gut during a response to mucosal pathogens? What is there instead?
Toll like receptors - not expressed on apical surface
Have intracellular pattern recognition receptors
What occurs when cells have been invaded by pathogens in the mucosa?
Recognised by N0D1/N0D2 and NFkB signalling is initiated
- Which switches on pro-inflammatory cytokines
- Recognition by PRRs triggers innate response - DC activation - adaptive immunity
Where are pattern recognition receptors found in the mucosa?
Basal surface - not on the surface of cell as normal
How does salmonella evade the immune system
Escapes vacuoles and hides in cytosol
- Escapes cell surface PRRs
Name 2 pro-inflammatory cytokines
IL-1, IL-18
Name 2 anti-inflammatory cytokines
IL-10, TGF-beta
How does Shigella work?
Invades via mucosal cells - and kills cells
- Has a toxin that inhibits translation
- C.difficile - toxin A - inactivates GTPases
What do Helminths infections provoke?
Strong Type-2 responses
- Production of non-phagocytic cells - helps eliminate some of the larger infections
How is Crohns disease caused?
Over-activation of intracellular PRR N0D2, Atg16L1
- Autophagy - causes sustained microbial induced inflammation - innate mediated
