Mucosal Immunity

Question 1

what are the physiological functions of mucosal tissues

Answer 1

gas exchange
goof absorption
sensory activities
reproduction

Question 2

how do non-pathogenic antigens enter/ext mucosal cells

Answer 2

transcellular

paracellular - via tight junctions, passive but selective (variable and regulated)

Question 3

anatomical features of the gut mucosal immune system

Answer 3

intimate relationship between mucosal epithelial and lymphoid tissue
organised lymphoid structures unique to mucosal sites
specilaised antigen uptake mechanisms

Question 4

effector mechanisms of gut mucosal immune system

Answer 4

activated/memory T cell predominate
natural effector/regulatory T cells
(important in HIV)

Question 5

immunoregulatory environment features of gut mucosal immune system

Answer 5

balance between over-reacting and normal reactions;
active down regulation of immune system
inhibitory macrophages and tolerising dendritic cells

Question 6

where are intestinal lymphocytes found when immune response induced

Answer 6

found in organised tissue scattered throughout the intestine where they carry out effector functions

Question 7

what are Peyer’s patches

Answer 7

‘lymph node of the small intestine’;
covered in epithelium
contain specialised cells - M cells
contain dendritic cells, T cells and germinal centres

Question 8

M cells

Answer 8

characteristic membrane ruffles

Question 9

describe an immune response of gut mucosal immune system

Answer 9

1. M cells take up antigen via endocytosis and phagocytosis
2. antigen transported across M cell in vesicles and released at basal surface
3. antigen is bound by dendritic cells - activating T cells

Question 10

how do dendritic cells come into contact with antigens

Answer 10

expose antigen to T cells;

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

Question 11

compartments of gut mucosal immune system

Answer 11

epithelium

lamina propria

Question 12

lamina propria of gut mucosal immune system

Answer 12

main immune response to pathogen after immune response activated - all immune response cells present

Question 13

entry of T cells to Peyer’s patch

Answer 13

via blood vessels

directed by homing receptors CCR7 and L-selectin

Question 14

T cell function in Peyer’s patches

Answer 14

1. encounter antigen transported across M cells and become activated by dendritic cells
2. T cells then drain via mesenteric lymph nodes to thoracic duct and return to the gut via bloodstream
3. activated T cells expressing alpha4:beta7 integrin and CCR9 home to gut (lamina propria and intestinal epithelium of small intestine)

Question 15

function of gut homing effector T cells

Answer 15

bind to MAdCAM-1 on endothelium

the gut epithelial cells will express chemokines specific for gut-homing T cells

Question 16

MAdCAM

Answer 16

found on endothelium and in vasculature of other mucosal sites

Question 17

why is unified recirculation compartment of common mucosal immune system important

Answer 17

allows for lymphocytes primed in the gut to migrate to other mucsal sites
passive immunity transferred in breast milk
vaccine developments (e.g. HIV)

Question 18

antibodies of humoral intestinal response

Answer 18

IgA - most abundant
IgM - 15%
IgG - 5%

reverse of systemic immune response

Question 19

IgA function in gut mucosal immune system

Answer 19

1. IgA binds to receptor on basolateral face of epithelial cell
2. enters via endocytosis
3. transcytosis to apical face of epithelial cell
4. IgA dimer (secretory component) released at apical face of epithelial cell - can now bind and neutralise pathogens and toxins

Question 20

describe intraepithelial lymphocytes (IEL)

Answer 20

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

Question 21

gut mucosal immune response to virus

Answer 21

1. infected cell displays viral peptide to CD8+ IEL via MHC class I
2. activated IEL kills infected epithelial cell by perforin/granzyme and Fas-dependent pathways
3. epithelial cells undergo stress and express MIC-A and MIC-B
4. NKG2D on IELs bind to MIC-A,B - activating IEL. CD8alpha:alpha homodimers bind to TL
5. IEL kills stressed cell in perforin/granzyme pathway

Question 22

how do epithelium cells become stressed

Answer 22

as a result of;
infection
damage
toxic peptides

Question 23

how is the balance between protective immunity and homeostasis maintained

Answer 23

discrimination between pathogen and innocuous antigens
oral tolerance
T cell and IgE mediated responses inhibited

Question 24

oral tolerance

Answer 24

default response to oral administration of protein state of specific peripheral unresponsiveness

Question 25

mechanisms of mucosal hyporesponsiveness

Answer 25

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