10. Coordination of tissue-specific memory Flashcards
Structure
- Importance of tissue-specific responses
- Response 1: Lymphoid structures
- Response 2: Resting cell subsets
- Response 3: Dendritic cell conditioning
Why are tissue-specific responses so important?
1.1
Provision of maximum immune protection. Pathogens exploit all available niches in the body, meaning that a diverse set of protective methods are required for the diverse set of locations.
How are lymphoid structures important for tissue-specific responses? Key point
2
Lymphoid structures coordiante immune responses by bringing activated DCs and naive lymphocytes together, and provide fast, coordinated responses.
What are the three types of lymphoid structure?
2.1
- Primary: Produce virgin lymphocytes.
- Secondary: Sites for activated lymphocytes
- Tertiary: Post-natal/ectoopic
Give an example of primary lymphoid structures?
2.2
Thymus, and bone marrow
Give examples of secondary lymphoid tissues
2.3
- Lymph nodes
- Spleen
- Gut/Mucosal/Nasal Associated Tissues (GALTs/MALTs/NALTs)
Example: GALTs include the MLN (Mesenteric Lymph Nodes), Peyer’s Patches, and Portal Lymph Nodes.
Give an example of a tertiary lymphoid structure
2.4
Isolated lymph node follicles
How do lymphoid structures develop?
2.5
- Retinoic acid induces CXCL13 (Chemokine) by mesenchymal cells
- This attracts precursor LTi cells from the blood to form first cell clusters
- LTi-clustering facilitates signalling through TRANCER
- This leads to induction of LTα1β2 by pre-LTi cells, which then mature
- Interaction of LTα1β2-epxressing cells with LTβR cells, which causes differentiation that causes chemokine, adhesive and cytokine molecules
- A particularly important molecule is CCR7, which supports the attraction of more hematopoeitic stem cells
- This leads to lymph node growth
Why are lymphoid structures so important?
2.6
Making fast, coordinated responses localised in different organs. Acting as an organiser for DCs and naive T-cells. Integration of responses between different tissues
Why are unique cell subsets important? Key point
3
Different tissues have different functions, and therefore different challenges. Different immune cell subsets will be present in different tissues, allowing for more specific responses.
3 main unique resting cell types in gut
3.1
- Unique lymphocytes
- Unique IgA production from B-cells
- Specialised enterocytes
Examples of gut-associated cell lymphocytes
3.2
- Mesenteric lymph node lymphocytes
- Peyer’s Patch lymphocytes
- Lamina Proparia lymphocytes
- Intra-Epithelial Lymphocytes
Function/Importance of IgA antibodies in the gut?
3.3
Dimeric antibodies that are good for agglutination and blocking. Production of IgA is strongly suported by T-cell production of TGFβ, and is secreted across enterocytes and epithelium of the bile duct.
Important for the regulation of gut microbial communities
How are enterocytes important for specific responses in the gut?
3.4
Enterocytes usually absorb and secrete water.
- Important defensive properties (i.e., synthesis of protective mucus over the epithelium, and production of IgA)
- Specialised enterocytes (Paneth cells secrete defensins, Goblet Cells secrete mucus, Intermediate cells and Enterochromaffin cells that regulate smooth muscle function)
- Microfold (M) cells. Specialised enterocytes that cover the dome of Peyer’s patches. Capture and delivery antigens to the immune system.
What are the two states of dendritic cells?
4.1
- Steady state (no infection, prolonged conditioning)
- Inflammatory state (brief conditioning with inflammatory cytokines)
What is T-cell homing?
4.2
When derivatives drive T- and B-cells to express tissue homing receptors, and brings them to the lymph nodes to meet the DCs
How does Vitamin A drive gut T-cell homing?
4.3
- Gut DC converts VitA to Retnoic Acid after activation in the MLN
- This induces α4β7
- α4β7 binds MAdCAM, αEβ7 (binds E-cadherin) and CCR9 (binds CCL25/TECK)
- This allows for lymphocyte homing to the gut
How does Vitamin D drive skin T-cell homing?
4.4
- Skin DCs transport VitD metabolites to a Peripheral LN
- T-cells and B-cells there have an RXR-VDR receptor
- The RXR-VDR receptor induces CCR4, which binds CCL17, and CCR10, which binds CCL27
- These molecules allow for lymphocyte homing to the skin
