Mucosal Immunity Flashcards
mucosal tissue
gas exchange
food absorption
sensory activities
reproduction
all functions critical to life
epithelial cells
passive but selective variable and regulated transcellular tight junction paracellular
afferent lymphatic vessel
brings antigens into lymph node
mostly on dendrites
gut mucosal immune system
specialised antigen organisation and uptake
memory T cell predominate
immunoregulatory environment
peyers patch
covered by an epithelial layer containing specialised cells called M(mricofoam) cells which have characteristic membrane ruffles
m cells are often a target for pathogen
due to less mucosal protection
how do m cells take up antigens
endocytosis and phagocytosis
antigen is transported across the m cells in vesicles
released at the basal surface
actives T cells
due to antigen binding by dendritic cells
dendritic cells
can extend processes across the epithelial layer to capture antigen from the lumen of the gut
what does the mucosal immune system consist of
distinct compartments
epithelium and lamina propria
lamina propria
dendritic cell, plasma cell macrophage, CD4 & 8 T cell, mast cell, IgA
epithelial layer
CCR9, DC,
alpha4-beta7 integrin
coeliac disease
T cells enter peyers patches
directed by the homing receptors CCR7 and l-selectin
T cells in peyers
encounter antigen transported across m cells and become activated by dendritic cells
activated t cells
drain bua mesenteric lymph nodes to the thoracic duct and return to the gut via bloodstream
activated T cells expressing alpha4-beta7 integrin and CR9
home to the lamina propria and intestinal epithelium of small intestine
MadCAM-1 on endothelium
gut-homing effector T cells bind
found in the vasculature at musical sites
humoral intestinal response
IgA - mostly produced in gut
IgA1 : IgA2
3: 2 = gut
10: 1 = periphery
dimeric - four antigen binding sites
IgM
IgG
systemic hormal immune repsonse
reversal
IgA - monomeric
IgA is transported across the lumen of the gut
binds to receptor on basolateral face of epithelial cell
endocytosis
transcytosis to apical face of epithelial cell
release of IgA dimer at apical face of epithelial cell
secreted IgA
binds and neutralises pathogens and toxins on the gut surface
bind and neutralise antigens internalised in endosomes
export toxins and pathogens from the lamina propria while being secreted
special T cells in the gut
intraepithelial lymphocytes
expression of aphaE:beta7 intern anchors them in the epithelium
2 types with different recognition mechanism
intra-epithelial lymphocytes (IELs)
lie within the epithelial lining of the gut
CD8+ T cells
virus infects mucosal epithelium cell
infected cell displays viral peptide to CD8 IEL via MHC class 1
activated IEL kills infected epithelial cell by perforin/granzyme and fas-dependent pathways
epithelial cells undergo stress as a result of infection
express MIC-A and MIC-B
NKG2D on IELs bind to MIC-A,B and activated IEL
CD8 alpha:alpha homodimers also bind to TL
activated IEL
kills the stressed cell via the perforin/granzyme pathway
balance between protective immunity and homeostasis
discriminating between pathogen and innocuous antigens
oral tolerance
T and IgE responses inhibited more than IgG responses
mucosal hyporesponsiveness
commensal organisms help regulate local hyporesponsiveness - PPAR gamma
anergy or deletion of antigen specific T cells - no costimulation
generation of regulatory T cells - weak costimulation
role of intestinal mucous immunity in disease
infectious disease primary immunodeficiency allergy coeliac disease IBD
mucosal response to infection and regulation of mucosal immune reponses
innate mechanisms eliminate most intestinal infections rapidly
activation through ligation of pattern recognition receptors
intracellular sensore in epithelial cells, PRR, activate the NFkB pathway
gene transcription and production of cytokines, chemokine and defensives
activation of underlying immune response
outcome of infection by intestinal pathogens
determined by a complex interplay between the microorganisms and the host IR
naive CD4 T cells are activated
during helminth infection and can differentiate to Th1 or Th2 effector cells
Th2 cell effector functions
produce IL-13, IL-5
induces epithelial cell repair and mucus and activated eosinophils
drive B cells to produce IgE
drive mast cell recruitment via IL-3, IL-9
specific IgE arms mast cels against helminths
Th1 cell effector functions
activate macrophages
activate B cells to produce IgG2a
infected dendritic cells
shuttle virus from the site of exposure to the regional lymph nodes where they concentrate virus particles and infect CD4+ T cells
mucosal disorder associated with primary immunodeficienct
all associated with mucosal abnormalities
CVID - adults
recurrent sinopulmonary and GI infections
failure to differentiate into Ig secreting cells
XLA - childhood. after 6 months of age
sinoplumonary and GI infections and devastating systemic manifestations
no B cells / agammaglobulinaemia
CGD - childhood
staphylococcus aureus/inflammatory granulomaspneumona, liver abscess, perianal abscess, skin abscess
failure of phagocyte respiratory burst
SCID - childhood
profound defect in t and B cell immunity
SCID - childhood
profound defect in t and B cell immunity
food allergy
type 1 hypersensitivity reaction initiated by crosslinking of allergen specific IgE on the surface of mast cells with the specific allergen
memory response- immune system must be primed
IgE secreted by plasma cells
binds to a high-affinity Fc receptor FcRI on mast cells
activated mast cells
provide contact and secreted signals to B cells to stimulate IgE production
coeliac disease - gluten sensitive enteropathy
genetically linked, autoimmune disorder
causes damage to the small intestine leading to malnutrition
tigger unknown
genetic susceptibility HLADQ2/HLADQ8
immunopathology T cell/IEL mediated
coeliac disease has small intestine with villous atrophy
villi gone
epithelium damage
low absorption capacity - malnutrition
diagnosing coeliac disease
NICE guidelines
biopsy - adults
serology - paediatrics
who goes for a biopsy
IgA anti-tissue transglutaminase autoantibodies
beware IgA deficiency and false negatives
crohns disease
focal and discontinuous inflammation with deep and eroding fissures +/- granulomas
ulcerative colitis
restricted to rectum and colon
starts in rectum and moves proximally and contiguously - can develop extra-intestinal manifestations
inflammation and ulceration just in surface mucosa
ulcerative colitis - treatment
non specific anti-inflammatory and immunosuppressive drugs
