Mucosal Immunity Flashcards
what are the physiological functions of mucosal tissues
gas exchange
goof absorption
sensory activities
reproduction
how do non-pathogenic antigens enter/ext mucosal cells
transcellular
paracellular - via tight junctions, passive but selective (variable and regulated)
anatomical features of the gut mucosal immune system
intimate relationship between mucosal epithelial and lymphoid tissue
organised lymphoid structures unique to mucosal sites
specilaised antigen uptake mechanisms
effector mechanisms of gut mucosal immune system
activated/memory T cell predominate
natural effector/regulatory T cells
(important in HIV)
immunoregulatory environment features of gut mucosal immune system
balance between over-reacting and normal reactions;
active down regulation of immune system
inhibitory macrophages and tolerising dendritic cells
where are intestinal lymphocytes found when immune response induced
found in organised tissue scattered throughout the intestine where they carry out effector functions
what are Peyer’s patches
‘lymph node of the small intestine’;
covered in epithelium
contain specialised cells - M cells
contain dendritic cells, T cells and germinal centres
M cells
characteristic membrane ruffles
describe an immune response of gut mucosal immune system
- M cells take up antigen via endocytosis and phagocytosis
- antigen transported across M cell in vesicles and released at basal surface
- antigen is bound by dendritic cells - activating T cells
how do dendritic cells come into contact with antigens
expose antigen to T cells;
can extend processes across epithelial layer to capture antigen from the lumen of the gut
compartments of gut mucosal immune system
epithelium
lamina propria
lamina propria of gut mucosal immune system
main immune response to pathogen after immune response activated - all immune response cells present
entry of T cells to Peyer’s patch
via blood vessels
directed by homing receptors CCR7 and L-selectin
T cell function in Peyer’s patches
- encounter antigen transported across M cells and become activated by dendritic cells
- T cells then drain via mesenteric lymph nodes to thoracic duct and return to the gut via bloodstream
- activated T cells expressing alpha4:beta7 integrin and CCR9 home to gut (lamina propria and intestinal epithelium of small intestine)
function of gut homing effector T cells
bind to MAdCAM-1 on endothelium
the gut epithelial cells will express chemokines specific for gut-homing T cells
MAdCAM
found on endothelium and in vasculature of other mucosal sites
why is unified recirculation compartment of common mucosal immune system important
allows for lymphocytes primed in the gut to migrate to other mucsal sites passive immunity transferred in breast milk vaccine developments (e.g. HIV)
antibodies of humoral intestinal response
IgA - most abundant
IgM - 15%
IgG - 5%
reverse of systemic immune response
IgA function in gut mucosal immune system
- IgA binds to receptor on basolateral face of epithelial cell
- enters via endocytosis
- transcytosis to apical face of epithelial cell
- IgA dimer (secretory component) released at apical face of epithelial cell - can now bind and neutralise pathogens and toxins
describe intraepithelial lymphocytes (IEL)
special T cells in the gut;
cytotoxic T cells
restricted antigen receptor repetoire
express alphaE:beta7 integrin, anchoring them in he epithelium
2 types with different recognition mechanisms
immunopathology coeliac disease
gut mucosal immune response to virus
- infected cell displays viral peptide to CD8+ IEL via MHC class I
- activated IEL kills infected epithelial cell by perforin/granzyme and Fas-dependent pathways
- epithelial cells undergo stress and express MIC-A and MIC-B
- NKG2D on IELs bind to MIC-A,B - activating IEL. CD8alpha:alpha homodimers bind to TL
- IEL kills stressed cell in perforin/granzyme pathway
how do epithelium cells become stressed
as a result of;
infection
damage
toxic peptides
how is the balance between protective immunity and homeostasis maintained
discrimination between pathogen and innocuous antigens
oral tolerance
T cell and IgE mediated responses inhibited
oral tolerance
default response to oral administration of protein state of specific peripheral unresponsiveness
mechanisms of mucosal hyporesponsiveness
commensal organisms regulate local hyporesponsiveness - PPAR gamma
immune-suppression and induced switching of B cells to IgA production;
anergy or deletion of antigen specific T cells - no costimulation
generation of regulatory T cells by dendritic cells - CD4+ TGF beta producing Th3 cells - weak costimulation
