TRUE OR FALSE: gamma delta t lymphocytes of the gut-associated immune system are capable of killing injured mucosal epithelial cells by inducing apoptosis?
TRUE
When the lymphocytes lining the mucosa of the respiratory tract are induced into effector status by a bacterial antigen, were do the lymphocytes subsequently migrate to?
The effector lymphocytes will leave the site of antigenic stimulation via the draining lymph nodes and distribute themselves to all mucosal surfaces
List three ways by which the mucosal-associated lymphoid system of the intestines differs to the immune system of the spleen and lymph nodes
- T cell repertoire + distribution differs (in intestines much more gamma delta T cells)
- there is normally oral tolerance to food HOWEVER if same food Ag was injected there wouldn’t be tolerance and there would be an immune response
- The main antibody produced by the mucosal-associated immune system is IgA whereas IgM and IgG are produced by lymphocytes of the spleen and lymph nodes
what are the primary and secondary lymphoid tissues innervated by?
sympathetic NS
Outline the processes by which enteric pathogens lead to the development of protective immunity
1) enteric pathogens enter via enterocytes/ M cells
2) M cells trigger infection by releasing cytokines (IL8) and chemokines (MCP1 and RANTES)
3. the chemokines attract neutrophils, monocytes, eosinophils and T lymphocytes.
4. M cells are involved in Ag presentation to macrophages in the Peyers patches
5. this in turn activates B and T cells
6. activated B cells = plasma cells secrete IgA
7. b cells migrate from intestinal mucosa to other mucosal surfaces
TRUE OR FALSE
Some of the features of an illness resulting from a bacterial infection including fever, sleepiness and loss of appetite are induced by effector lymphocytes traveling to the brain and influencing the areas of the brain responsible for temperature and appetite regulation
false
what are the physical barriers for the GIT mucosa?
- 1 cell thick layer of epithelium
- mucous
- gastric acid
- microflora
- proteolytic enzymes
- motility
What are the protective immune responses in the GIT?
- SIgA
- cell mediated immunity
- T cells (CD4, CD8, gamma delta T cells, IELs)
- DCs, macrophages and NK cells
what are Peyer’s patches?
- consist of masses of lymphocytes arranged in follicles covered by M cells
what are M cells?
- specialised epithelium
- found in peyers patches
- microfold cells
- phagocytic
- take up Ag and present to APCs
what are the ways in which Ag can be captured by APCs in mucosal tissue?
1) M cells take up Ag and present down into peyers patch to DCs
2) DCs sit in lamina propriety with arms in btw epithelial cells -> can grab Ag
3) Ab that has been secreted and bound by Ag can be brought into lamina propria to DCs
which tissues make up the GALT?
1) Tonsils adenoids
- ring of lymphoid organs surrounds the entrance to the GI and respiratory tracts
2) Appendix
- lymphocytes + germinal centres
3) Peyer’s patches
- inductive sites
4) Solitary lymphoid nodules or scattered lymphoid cells
what are the protective mechanisms in the GALT?
non immune protection
1) 1 cell thick layer of epithelium
2) mucous
3) gastric acid
4) microflora
5) proteolytic enzymes
6) motility
GALT
- SIgA
- cell mediated immunity
- T cells (CD4, CD8, gamma delta T cells, IELs)
- DCs, macrophages and NK cells
what are intraepithelial lymphocytes?
- IELs -> effector T cells
- many of them are gamma delta T cells in the mucosal system
(other IELs incl CD8 alpha beta / CD8 alpha alpha T cells)
what happens in the lymphocyte circulation in the GALT?
- lymphocytes activated lured back to gut when they differentiate into effector cells
- effector lymphocytes activated in any mucosal tissue recirculates through all mucosal tissues
- endothelial cells in mucosal tissues express MadCAM (adhesion molecules that effector lymphocytes use to migrate into mucosal tissues)
which Ab isotype is the most abundant in gut secretions, which cell is it produced by?
- IgA is a dimer produced by plasma cells
- dimer formed by J chain joining cysteines in each monomer
- j chain attaches to receptor and is responsible for transporting of IgA and IgM across epithelium
what are the actions of IgA?
- neutralises viruses and bacterial enzymes
- activates complement by the alternative pathway
- bind antigens either in the lamina propria or in the cytoplasm of the enterocytes
- combined with antigens may bind to Fc receptors on phagocytic cells to opsonise antigens, initiate an oxidative burst and release inflammatory cytokines
what is oral tolerance?
- Hallmark of gut immunity
- Most Ag presented to the mucosal immune system induce tolerance
- Oral tolerance refers to the state of systemic hyporesponsiveness induced by feeding protein
- Immunologic nonresponsiveness to luminal Ags is more common than mucosal responsiveness
If an antigen induces inflammatory response in the gut what is it called and why does it happen?
- protective immunity
- Pathogenic microbes have virulence factors and PAMPs that override the default unresponsiveness of the gut
- inflammatory response during infection induces APCs to express co- stimulatory molecules > provide additional signal required for expansion of naïve lymphocytes
- Infected enterocytes release variety of cytokines and chemokines > recruit inflammatory cells
what are the mechanisms of oral tolerance?
1) anergy = T cells presented in the absence of co-stimulation
2) apoptosis of antigen specific T cell by apoptosis
3) Ag specific responses and T cells producing IL-4, IL-10 & TGF-β are suppressed by development of Treg cells
