gastrointestinal mucosal immunology - basic science Flashcards
what are cytokines
chemical mediators that regulate cell immune responses
what does the gastrointestinal tract represent
a major site of host-environment (luminal contents) interaction
Gastrointestinal epithelial barrier
Single layer of cells – different phenotypes
Physical barrier between host and environment
Rapid restitution to retain continuity
Selective permeability of water, ions, nutrients
Epithelial barrier growth dynamics
Lgr5+ stem cells in base of crypt
Proliferation and differentiation as move up the crypt
Cell shedding at tip
Autophagy important
Tight control by signalling molecules (epithelial cells/mesenchymal cells) – Wnt/B-catenin, Notch, BMP, Hedgehog
Develop Self-tolerance
Non-responsiveness to self antigens
Develop exogenous tolerance
Non-responsiveness to an enormous array of newly encountered environmental antigens (Food and Microbes)
Develop an effective Immune response
Elimination or control of infections, allergic and noxious agents
how do Gut dendrite cells and macrophages exist
exist as several phenotypes which have distinguishable cell markers and functions
what is the role of DC subsets and macrophage
presenting antigen and driving T cell differentiation eg. Th1 or Tregs
what is required fir the clearance of pathogens
Th1 cells and other proinflammatory cells eg Th17 cells are required
what is required for maintaining immune homeostasis and tolerance
Tregs (Tregs, Tr1, Th3)
what also contributes to mucosal tolerance
B cells through differentiation in plasma cells and IgA
what does the epithelial barrier have
important structure and function as part of immune defence
what is there a cross talk between
the epithelial barrier, microbiota and immune cells
what are M cells
specialised and organised parts of the immune system in the gut
what do cytokines do
they orchestrate and finely tune the immune response –pro-inflammatory and anti-inflammatory cytokines
what 3 signals determines T cell response
MHC/peptide-TCR
CD80-CD28
Cytokine
what are macrophages
phagocytic and ingest and kill foreign micro-organisms
describe more on macrophages
first line of defence system in the gut
Tissue resident and monocyte derived
sampling of particulate antigens
phagocytic
secrete cytokines eg IL-10 required for the survival of FoxP3+ Treg cells
Professional APCs to modulate adaptive immune response
describe IgA
- Binds to immune cells impacting their function eg phagocytosis, degranulation
- Antimicrobial
- Neutralises toxins
- Cross talk with microbiota tolerance
cytokines are key
communication between cells and drive function