Mucosal Immune Response

Question 2

important components of the mucosal barrier

Answer 2

gastric acid, pancreatic enzymes, bile acids, peristalsis, biofilm, secreted IgA and defensins, TIGHT JUNCTIONS (like a “force field” to prevent bacteria from coming in contact with immune cells)

Question 3

where are most of the immune cells in the gut?

Answer 3

lamina propia

Question 4

sequence of steps in mucosal defense to an invasive microbe

Answer 4

serum/mucosal factors (complement, Ig, antimicrobial peptides) ? neutrophils ? acute inflamm., macrophages ? lymphocyte response, clearance of pathogens, and resoration of homeostasis

Question 5

how does the gut sample the lumen contents?

Answer 5

M (microfold) cells that constantly “taste” bits of lumen; no mucos, no villi, selective uptake of antigen only

Question 6

lifecycle of an intestinal lymphocyte

Answer 6

born in bone marrow/thymus, migrates to Peyer’s patches where activated, expansion in MLN, homing back to intestinal lamina propia at sight of original matching antigen, but also to other mucosal surfaces

Question 7

preferential migration to mucosal sites results from?

Answer 7

expression of unique complementary adhesion molecules (by mucosal lymphocytes) and addressins (by endotherlial cells) basically tags the lymphocyte to migrate to mucosal epithelium

Question 8

lymphocytes express this unique complementary adhesion molecule

Answer 8

a4-b7 integrin

Question 9

mucosal endothelium expresses this addressin cell adhesion molecule

Answer 9

MAdCAM-1

Question 10

secretory IgA

Answer 10

most abundant Ig in the human body; prevents attachment and invasion of pathogenic bacteria by dimerizing with J chain and transcytosing across mucosal epithelial cells, where it blocks colonization and uptake of bacteria in the gut

Question 11

oral tolerance

Answer 11

antigen feeding induces tolerance to subsequent systemic antigen immunization – why we don’t have an immune response to everything we eat

Question 12

TH3

Answer 12

stimulated by dietary luminal antigen, suppresses immune response by release of TGFb and IL-10

Question 13

Tr1

Answer 13

stimulated by bacteria in the luminal antigen, supresses immune response by release by IL-10, TGFb

Question 14

There are also CD8 cells in the intestine that suppress by release of?

Answer 14

TGFb

Question 15

intestinal macrophages have these unique functional adaptations

Answer 15

release much fewer cytokines, do not express traditional surface molecules that activate immune response, “inflammation anergic” (still phagocytose)

Question 16

a defective innate immunity or decreased mucosal barrier function results in?

Answer 16

prolonged mucosal microbial exposure, T cell responses (Crohn’s ds)

Question 17

a lack of oral tolerance results in?

Answer 17

chronic inflammation (Crohn’s ds, ulcerative colitis, celiac ds)

Question 18

ulcerative colitis

Answer 18

diffuse inflamm of mucosa of colon, TH2 mediated

Question 19

Crohn’s disease

Answer 19

segmental inflamm of any part of GI tract, TH1/17 mediated (see nodularity, ulceration, narrowing)

Question 20

Crohn’s disease pathogenesis is a complex interplay between?

Answer 20

microbiota, environmental triggers, immune response, and genetic susceptibility

Question 21

we have engineered anti-____ monoclonal antibodies to decrease inflammatory response in Crohn’s disease

Answer 21

anti-TNF (infliximab), anti-IL-12/23 (Ustekinumab), anti-alpha4 (Natalizumab)

Question 22

What happened to patients on anti-alpha4 (natalizumab)? What was it replaced with?

Answer 22

acquired PML; anti-a4b7, antib7, antiMAdCAM