L13 - Mucosal Immunity

Question 1

Essential function of mucosal surfaces?

Answer 1

Gas exchange
Food absorption
Sensory activities
Reproduction

Question 2

What are the mucosal surfaces for entry of pathogens?

Answer 2

Mouth & respiratory contract

Gastrointestinal tract

Reproductive tract

Question 3

3 functions of the epithelium?

Answer 3

Lines mucosal surfaces defining border

Defends from invasion

selectively transports components essential for life to lamina/circulation

Question 4

What are the 2 ways that mucosal tissue is defined?

Answer 4

Scattered - lymphocytes dotted around

Organised - B cell and T cell areas concentrated in 1 area - drain the lymph nodes

Question 5

Anatomical features of the mucosal immune system?

Answer 5

Interactions between mucosal epithelia and lymphoid tissues

discrete compartments of diffuse lymphoid tissue and organised structures e.g. tonsils

specialised antigen-uptake mechanisms e.g. M cells in Peyer’s patches

Question 6

Effector mechanisms of the mucosal immune system?

Answer 6

Presence of distinctive microbiota

Secretory IgA antibodies

activated ‘natural’ effector T cells present

Activated T cells predominate even without infection

Question 7

Immunoregulatory environment of the mucosal immune system?

Answer 7

Active downregulation of immune response

Inhibitory macrophages & tolerance-inducing DCs

Question 8

The 4 cells that stem cells differentiation in mucosal tissue leads to?

Answer 8

Enterocytes/colonocytes
Paneth cells
Goblet cells
Enteroendocrine cells

Question 9

function of enterocytes/colonocytes?

Answer 9

absorptive

AMPs production

Question 10

function of paneth cells?

Answer 10

AMPs

Question 11

function of goblet cells?

Answer 11

mucus secretion - lubricate food and prevent bacteria binding

Question 12

function of enteroendocrine cells?

Answer 12

neurohumoral factors secretion - enzymes

Question 13

What are M cells?

Answer 13

sample environment and phagocytose pathogens

Question 14

Antimicrobial protein families in intestine and skin?

Answer 14

REG3y - bind onto carbs

BD1/2/3/4 - produced by sebaceous gland

RNases

Lactoferrin - ferrous ions

Calprotectin - binds Ca ions

Question 15

What is the dominant class of Ab on mucosal surfaces?

Answer 15

IgA
IgA1 - lung
IgA2 - colon

Question 16

Major function of IgA?

Answer 16

IMMUNE EXCLUSION

IgA adsorb on the mucus layer - interactions between carbohydrates

IgA do NOT activate complement classical pathway - does NOT promote inflammation

Question 17

What are IgA resistant to?

Answer 17

protease

Question 18

What are the immune cells of the mucosa?

Answer 18

Intraepithelial lymphocytes (IELs)

Question 19

What do IELs recognise?

Answer 19

epithelial cells expressing abnormal phenotypes resulting from stress/infection

Question 20

What are ILCs?

Answer 20

Innate Lymphoid cells

Question 21

Group 1 ILCs?

Answer 21

ILC1
NK cells
IFNy
similar to Th1

Question 22

Group 2 ILCs?

Answer 22

ILC2
Trigger soluble antibody response
similar to Th2

Question 23

Group 3 ILCs?

Answer 23

ILC3
Inflammatory response & epithelial type immunity
similar to Th17 & Th22

Question 24

What samples the mucosal compartments?

Answer 24

Distinct DCs e.g. CD103+

Question 25

What is MadCAM?

Answer 25

on vasculatare of all mucosa | Gut homing lymphocytes

Question 26

Why are host-commensal interactions needed in the gut?

Answer 26

help to digest food responsible for extraction & synthesis of nutrients compete with pathogens inhibit pathway that is required for pathogen uptake

Question 27

What gut infection can arise when antibiotics are used?

Answer 27

Clostridium difficile altered gut environment and pathological inflammation

Question 28

What is happy equilibrium "physiological inflammation"?

Answer 28

Commensal bacteria constantly triggering slight inflammation important in calming the immune response

Question 29

How does salmonella cause infection?

Answer 29

kill M cells - infect macrophages and epithelial cells invade luminal surface of epithelial cells enter phagocytes cells that are sampling gut luminal contents

Question 30

How does shigella cause infection?

Answer 30

physically kills M cells invade basal surface of epithelial cells and spread cell-wall peptides binds NOD1 - activate NFkB pathway activated epithelium secretes CXCL8 - recruits neutrophils

Question 31

What does shiga toxin do?

Answer 31

inhibit translation

Question 32

What does Clostridium difficile toxin A do?

Answer 32

inactivates GTPase

Question 33

What does rotavirus NSP4 do?

Answer 33

disrupts tight junctions

Question 34

What response do helminth infections provoke?

Answer 34

Th2 IL13 - epithelial cell repair M2 macrophages activated Driver B cells to produce IgE IL5 recruits eosinophils IL3/IL9 mast cell recruitment

Question 35

Aberrant mucosal immunity?

Answer 35

Crohn's - NOD2, Atg16L1 - phagoctyoses intracellular bacteria Coeliac - HLA-DQ2 - binds gliadin C. difficile