Mucosal Immunity

Question 1

mucosal tissue

Answer 1

gas exchange
food absorption
sensory activities
reproduction

all functions critical to life

Question 2

epithelial cells

Answer 2

passive but selective
variable and regulated
transcellular
tight junction
paracellular

Question 3

afferent lymphatic vessel

Answer 3

brings antigens into lymph node

mostly on dendrites

Question 4

gut mucosal immune system

Answer 4

specialised antigen organisation and uptake

memory T cell predominate

immunoregulatory environment

Question 5

peyers patch

Answer 5

covered by an epithelial layer containing specialised cells called M(mricofoam) cells which have characteristic membrane ruffles

Question 6

m cells are often a target for pathogen

Answer 6

due to less mucosal protection

Question 7

how do m cells take up antigens

Answer 7

endocytosis and phagocytosis

Question 8

antigen is transported across the m cells in vesicles

Answer 8

released at the basal surface

Question 9

actives T cells

Answer 9

due to antigen binding by dendritic cells

Question 10

dendritic cells

Answer 10

can extend processes across the epithelial layer to capture antigen from the lumen of the gut

Question 11

what does the mucosal immune system consist of

Answer 11

distinct compartments

epithelium and lamina propria

Question 12

lamina propria

Answer 12

dendritic cell, plasma cell macrophage, CD4 & 8 T cell, mast cell, IgA

Question 13

epithelial layer

Answer 13

CCR9, DC,

Question 14

alpha4-beta7 integrin

Answer 14

coeliac disease

Question 15

T cells enter peyers patches

Answer 15

directed by the homing receptors CCR7 and l-selectin

Question 16

T cells in peyers

Answer 16

encounter antigen transported across m cells and become activated by dendritic cells

Question 17

activated t cells

Answer 17

drain bua mesenteric lymph nodes to the thoracic duct and return to the gut via bloodstream

Question 18

activated T cells expressing alpha4-beta7 integrin and CR9

Answer 18

home to the lamina propria and intestinal epithelium of small intestine

Question 19

MadCAM-1 on endothelium

Answer 19

gut-homing effector T cells bind

found in the vasculature at musical sites

Question 20

humoral intestinal response

Answer 20

IgA - mostly produced in gut

IgA1 : IgA2

3: 2 = gut
10: 1 = periphery

dimeric - four antigen binding sites

IgM
IgG

Question 21

systemic hormal immune repsonse

Answer 21

reversal

IgA - monomeric

Question 22

IgA is transported across the lumen of the gut

Answer 22

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

Question 23

secreted IgA

Answer 23

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

Question 24

special T cells in the gut

Answer 24

intraepithelial lymphocytes

expression of aphaE:beta7 intern anchors them in the epithelium

2 types with different recognition mechanism

Question 25

intra-epithelial lymphocytes (IELs)

Answer 25

lie within the epithelial lining of the gut | CD8+ T cells

Question 26

virus infects mucosal epithelium cell

Answer 26

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

Question 27

epithelial cells undergo stress as a result of infection

Answer 27

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

Question 28

activated IEL

Answer 28

kills the stressed cell via the perforin/granzyme pathway

Question 29

balance between protective immunity and homeostasis

Answer 29

discriminating between pathogen and innocuous antigens oral tolerance T and IgE responses inhibited more than IgG responses

Question 30

mucosal hyporesponsiveness

Answer 30

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

Question 31

role of intestinal mucous immunity in disease

Answer 31

``` infectious disease primary immunodeficiency allergy coeliac disease IBD ```

Question 32

mucosal response to infection and regulation of mucosal immune reponses

Answer 32

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

Question 33

outcome of infection by intestinal pathogens

Answer 33

determined by a complex interplay between the microorganisms and the host IR

Question 34

naive CD4 T cells are activated

Answer 34

during helminth infection and can differentiate to Th1 or Th2 effector cells

Question 35

Th2 cell effector functions

Answer 35

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

Question 36

Th1 cell effector functions

Answer 36

activate macrophages activate B cells to produce IgG2a

Question 37

infected dendritic cells

Answer 37

shuttle virus from the site of exposure to the regional lymph nodes where they concentrate virus particles and infect CD4+ T cells

Question 38

mucosal disorder associated with primary immunodeficienct

Answer 38

all associated with mucosal abnormalities

Question 39

CVID - adults

Answer 39

recurrent sinopulmonary and GI infections | failure to differentiate into Ig secreting cells

Question 40

XLA - childhood. after 6 months of age

Answer 40

sinoplumonary and GI infections and devastating systemic manifestations no B cells / agammaglobulinaemia

Question 41

CGD - childhood

Answer 41

staphylococcus aureus/inflammatory granulomaspneumona, liver abscess, perianal abscess, skin abscess failure of phagocyte respiratory burst

Question 42

SCID - childhood

Answer 42

profound defect in t and B cell immunity

Question 43

SCID - childhood

Answer 43

profound defect in t and B cell immunity

Question 44

food allergy

Answer 44

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

Question 45

IgE secreted by plasma cells

Answer 45

binds to a high-affinity Fc receptor FcRI on mast cells

Question 46

activated mast cells

Answer 46

provide contact and secreted signals to B cells to stimulate IgE production

Question 47

coeliac disease - gluten sensitive enteropathy

Answer 47

genetically linked, autoimmune disorder causes damage to the small intestine leading to malnutrition tigger unknown genetic susceptibility HLADQ2/HLADQ8 immunopathology T cell/IEL mediated

Question 48

coeliac disease has small intestine with villous atrophy

Answer 48

villi gone epithelium damage low absorption capacity - malnutrition

Question 49

diagnosing coeliac disease

Answer 49

NICE guidelines biopsy - adults serology - paediatrics who goes for a biopsy IgA anti-tissue transglutaminase autoantibodies beware IgA deficiency and false negatives

Question 50

crohns disease

Answer 50

focal and discontinuous inflammation with deep and eroding fissures +/- granulomas

Question 51

ulcerative colitis

Answer 51

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

Question 52

ulcerative colitis - treatment

Answer 52

non specific anti-inflammatory and immunosuppressive drugs