wk 2 2 mucosal immunity Flashcards
physiological functions of mucosal tissues
gas exchange food absorption sensory activities reproduction #
glands which secrete mucosas
lachrymal salivary mammary kidney uro-genital tract
where would classic lymph nodes be located in GI
mesentery
distinctive anatomical featurees of gut mucosal immune system
intimate relaitonship betwen mucosal epithelia and lymphoid tissue
special structure
specialised mechanisms
effector mechanisms of gut mucosal immunity
activated/memory t cell predominate
‘natural’ effector/ regulatory T cells
immunoregulatory of gut mucosal cells is done by (2)
active down regulation of immune response
inhibitory maccrophages and tolerising dendritic cells
disease which causes constant inflammation of gut
chron’s disease
area of activationin gut immune cells
peyer’s patch
which are is covered by an epithelial layer containing specialised cells called M cells, tht have characteristic membrane ruffles (M= microvilli)
peyer’s patch
microvilli increases
surface area
where are dendritic cells located in peye’s patch
intimately close to M cell, directly behind
other than help from M cells, how can dendritic cells provide immune response
can do through lamina propria, extend across the layer to catch the antigen from the lumen of the gut
`cells located in gut epithelium
CD4 dendritic cell CD8 macrophage mast cell dendritic cell IgA plasma celll
MADCAM-1 is a
molecular adresin
on epithelium
t/f MAdCAM is onyl found in gut
false
most abundant antibody in intestinal response
IgA (80%) - mostly IgA2
also dimeric
(IgM = 15%)
(IgG=5%) - most abundant in systemic
name of recdptor which allows binding of IgA to epithelial face and into luminal gut
poly-Ig receptor
3 ways IgA provides protection in gut
secreted to gut and neutralise pathogens and toxins
bind to pathogens internalsied in endosomes and neutralise
can export toxins from within lamina propria while being secreted
t/f IgM can replace IgA
true
poly-Ig can bind to dimerics, IgM also dimeric
not as good but works for those with immune defiency
outline the characteristics of special T cells of gut
expresses alphaE:Beta7 = anchoring to epithelium, does not move
activated
restricted antigen receptor
what happens when a virus infects mucosal epithelium cell
infected vell - displays viral peptide to CD8 IEL (MHC class I)
activated IEL kills infected epithelium by perforin/granzyme and Fas-dependent pathways
when epithelum cells undergo stress (infection, damage, toxic peptides) and express MIC-A and MIC-B, what happens
IEL T cells bind to MIC-A,B via NKG2D, activates, CD8alpha:alpha bind to TL, kills strssed cell via perforin/granzyme pathway
what happens in coeiliac disease
more death of epithelium cells than production
epithelium becomes flat, reduces absorption (surface area decreases)
define oral tolerance
default response too oral administration of prootein state of specific peripheral unresponsiveness
which responses require a mediated response the most in gut
T cell
IgE
t/f commensal organisms help cause hyperesponsiveness of mucosa
false
regulates local hyporesponsiveness
how are T cells mediated 2
anargy/deletion of T cells
generation of regulatory T cells
both immunosuppresive and induce B cells switching to IgA production
3 things which when present in commensal bacteria inhibit dendritic cell maturation
PGE2
TGF-beta
TSLP
define t cell anargy
tolerance mechanism in which the lymphocyte is inactivated following antigen encounter, yet remains alive in a hyporesponsiveness state
MAdCAM-1 is an adressin molecule, what is this
ligand receptor
when would dendritic cells be activated in gut
if microorganisms penetrate epithelium
dxpress strong co-stimulatory ligands and induce CD4 T cells to differentiate into effector Th1 and Th2 cells
what activates the NFkB pathway
intracellular sensors in epithelial cells (PRR)
defensins are
anti-microbial peptides
how does an infection develop
if some of the immune response cells are over taken, oesnt work properly and so infections able to spread
naive CD4 T cells can activate into effector Th2 or Th1 cells, what does each produce and effect
Th2 - IL-13 produced, epithelial repair and mucus secretion
- IL-5 produced, recruits/activates eosinophils, promotes IgA production
- drive B cells to produce IgE (main immuno for parasites)
Th1- IL-3,IL-9 activates mast cells (histamine, TNFalpha, MMCP)
- activates macrophages
- activates B cells, produce IgG2a
helminths infection is a
parasites infection
which effector Th cell is appropriate fro helminths infection
Th2
th1 will lead to a chronic infection, IgG good at removing bacteria not parasites
how does HIV infect
infects dendritic cells, expresses co-stimulation and moves to lymph nodes
finds more hosts, infects CD4T cells (activated) - these migrate to carry out effector functions, widespread dissemination
primary immunodeficiency disorders present usually with
mucosal dysfunction
t/f selective IgA defiency is only viral
false
only bacterial
common variable immunodefiency is due to
failur to differentiiate into Ig secreting cells
- low immunoglobulins (IgA ect)
- bacterial infection
CVID associated infections are
recurrent sinopulmonary and GI infections
XLA (x-length agammaglobulinaemia) only affects males t/f
true
when does XLA present, why
7/8months
immunoglobulin from mother (IgG, dimeric IgA) depletes, dont make their own
what is the defect found in XLA
no b cells
agammaglobulinaemia
associated conditions of CGD (Chronic Granulomatous Disease)
granulomas-pneumona, liver abscess, perianal abscess, skin abscess
associated bacteria of CGD
staph aureus
CGD is failure of
phagocyte respiratory burst
how is CGD treated
bone marrow transplant
Severe Combined Immunodefiency (SCID) appears
in first few weeks
SCID is a profound defect in
t and b cell imunity
associated conditions of SCID
oral candidiasis
chronic diarrhoea
interstitial pneumonotitis
how is type 1 hypersensitivity initiated
crosslinking of allergen specific IgE on surface of mast cells with specific allergen
triggers for anaphylaxis 3
venom
drugs
food
due to systemic arrival (IgE secreted by plasma)
how does food cause anaphylaxis
undigested proteins absorbed across gut, enters vasculature
why is avoidance key for allergens
every time allergen in presented to immune, stronger memory response
coeliac disease is
hypersensitivity (non-allergic) to gluten
treatment for coeliac
gluten-free diet
gamma interferon from gluten specific t cell activat eepithelial cells which produe IL-15, what does this induce
proliferation and activation of IEL
intra-epithelial lymphocytes
activation of IEL and T cells causes
death of epithelial cells
characteristics of coeliac intestine
gut flattens (lymphocytes/IELs kill epithelial quicker than they can be produced) lots of IELs along mucosal surface loss of villi
2 genes associated with coeliac disease
HLA-DQ2
HLA-DQ8
associated antibody production of coeliac disease 3
anti-gliadin
anti-endomysal
anti-tissuue transglutaminase
how is coeliac disease diagnosed in adults
adults - serology determines if they have anti-tissue transglutaminase
then biopsy
what may cause a patient coeliac disease be misdiagnosed
if they are IgA deficient - wont product anti-tissue transglutaminase
t/f b cells can present antigens in secondary response
true
why is if there is no gluten, there is no antibody
b cell binds to gluten complex contsinign transglutminase
t cell binds and produces anti-gluten
b cells instead produces antibodies for transglutaminase
characteristics of Crohn’s disease
focal and discontinuous inflammation with deep eroding fissures
also granulomas may be present
t/f granulomas in ulcerative colits
false -
where does ulceritive colitis begin
rectum, moves proximally and contiguously
ulcerative colitis is due to
distortion of crypts with infiltration of monocytes/neutrophils and plasma cells
t/f inflammation/ulceration of ulcertive colitis only affects surface of mucosa
true
treatment for ulceritive colitis
non-specific anti-inflammaotry and immunosuppressive drugs
steroids/azathioprine/cyclosporin/methotrexate
anti-TNF alpha
