Mucosal Immunity

Question 1

Mucins

Answer 1

serve barrier function and secretion of mucous

• gastrointestinal mucins are O-linked oligosaccharides
• serve a barrier function and can sequester pathogens

Question 2

epithelial cells

Answer 2

• play role in innate immune response
• express TLR’s and NLR’s to recognize bacteria through ligation of TLR, will secrete cytokines and chemokines
• have lowered response to gut flora on floor of lumen. NLR receptors are in cytoplasm and TLR’s are on basolateral side - resulting in bacteria present in lumen not triggering a strong immune response, if bacteria invades into cell it triggers NLR or if it gets into lamin propria will trigger TLR.
• form barrier and serve antibacterial functions
• can release defensins and cytokines and chemokines if TLR and NLR are activated

Question 3

paneth cells

Answer 3

bottom of crypts, secrete antimicrobial substances and defensins. part of innate immunity.

Question 4

Peyer’s patches

Answer 4

found directly under epithelium, not encapsulated like lymph nodes, but have loose organizaiton of T and B cells and AP cells

Question 5

M Cells

Answer 5

• innate immunity
• antigen sampling
• embedded in epithelial layer, lack microvilli that epithelial cells do, but transport antigens in from lumen to Peyer’s patches for antigen presentation. dendritic cells pick up the antigen and present it to peyer’s patches

Question 6

dendritic cells

Answer 6

• adaptive immunity
• in lamina propria can extend arms through epithelial surface and sample Ag’s. Once pick up Ag’s can move to mesenteric lymph nodes to present the Ag’s. T and B cells will them be activated and homed back to the lamina propria where they are needed.
• express IL-6 and TGF-beta

Question 7

mesenteric lymph nodes

Answer 7

where antigen presentation takes place

Question 8

plasma cells

Answer 8

secrete IgA into the gut lumen to dampen immune responses to pathogens

Question 9

T cell

Answer 9

• in lamina propria and epithelial layer

Question 10

Mast cells

Answer 10

also found in lamina propria

Question 11

Goblet cells

Answer 11

innate immunity

- mucus secreting-barrier function and antibacterial

Question 12

Defensins

Answer 12

• small cationic peptides that have anti-microbial properties and can activate other immune cells
• alpha-defensins produced by Paneth cells in small bowel, and by neutrophils
• beta-defensins produced by absorptive epithelial cells in the colon

Question 13

Adaptive immunity

Answer 13

• humoral immunity and IgA
• Th17 dominant cell-mediated immunity
• suppression of cell-ediated immunity : regulatory T cells are very important to limit response to normal flora

Question 14

FoxP3

Answer 14

• stimulation of making of T reg cells - will help dampen the negative immune responses to gut flora

Question 15

CD103 expressing

Answer 15

regulatory dendritic cells

- can make retinoic acid from vitamin A

Question 16

Lymphocyte homing in the gut directs cells to the lamina propria

Answer 16

dendritic cell with antigen –> mesenteric lymph nodes or peyer’s patches –> retinoic acid production –> alpha4beta7 on lymphocytes helps effector T or B cell back to the gut by binding of MadCAM on the endothelial cells of the gut lamina propria

• Only DC’s in the gut express retinal dehydrogenase (RALDH) which is necessary for synth of retinoic acid from Vitamin A
• Chemokine receptor CCR9 on lymphcytes binds the chemokine ligand on intestinal epthelial cells of small intestine
• Chemokine receptor CCR10 binds chemokine CCL28 expressed by colon

Question 17

IgA function

Answer 17

• serves a protective role, neutralizes biologically activa Ag’s
• secreted into gut lumen and prevents uptake of Ag’s by intestinal tract
• inhibits adherence of bacteria to epithelial surfaces
• can enhance innate immune factors

Question 18

Serum IgA

Answer 18

• present in low levels
• does not fix complement, thus it is anti-inflammatory in the gut and won’t trigger this response.
• prevents colonization without inflammation
• allows for clearnce of circulating Ag Ab complexes without inducing systemic inflammation

Question 19

humoral immunity: IgA class switching: T cell dependent

Answer 19

• Luminal Ag taken up and presented to Peyer’s patch. Activates naive CD4+ T cell which turns into activated helper T cell.
• Activated helper T cell presents to B cell via CD40/CD40L. B cell class switches to IgA. Plasma cell is transferred across epithelium where it can release IgA for mucosal immunity.

Question 20

Humoral immunity: IgA class switching: T cell independent

Answer 20

Bacterium/PAMP binds the TLR of the dendritic cell. Dendritic cell secretes APRIL, TGF-beta, and BAFF which stimulates the B cell to class switch to IgA secreting cell

Question 21

IgA transport

Answer 21

• J chain holds IgA dimers together and binds IgA receptors on mucosal epithelial cell when secreted from the B cells. The IgA complex travels through eh mucosal epithelial cells, where it is cleaved and makes its way into the lumen.

Question 22

cell mediated immunity

Answer 22

• intraepithelial CD8+ T cells
• have a limited T cell repetoire - dampens immune repetoire
• Lamina propria cells are mostly CD4+ cells

Question 23

Th17 cells

Answer 23

• CD4+Tcells that play a role in colonization and protection of the gut
• secrete IL-17 and IL-22
• overactive TH17 response can be inflammatory

Question 24

Th2 cells

Answer 24

protect against helminthic infections/ parasites

• secrete IL-4 and IL-13
• type I hypersensitivity to food allergies, results in inappropriate mast cell activation

Question 25

Regulation of immunity in the GI tract

Answer 25

- LP has high progortion of FoxP3 cells in order to dampen immunity - CD103+ Dendritic cells, retinoic acid, TGF-beta play important role in development of T regs - TGF-beta, IL-10, IL-2 are secreted for regulation

Question 26

Inflammatory Bowel disease: 2 diseases that can result

Answer 26

- Crohn's disease (affects the entire thickness of the bowel wall and most frequently the terminal ileum) - Ulcerative colitis (restricted to the colonic mucosa)

Question 27

Hx: abdominal pain, non-bloody diarrhea, anorexia over past 2 years, pain is in RLQ and cramping. weight loss and abdominal mass in right iliac fossa, and perianal fistulas. Endoscopy shows ulceration of esophagus and small intestine with perianal fistula and neutrophilic infiltration.

Answer 27

Crohn's disease; a type of IBD

Question 28

why does IBD occur?

Answer 28

1. dysregulated innate immune response: defective defensin expression or inadequate negative immune regulation to commensal organisms 2. Abnormal cell-mediated immunity: due to overactive Th17 response or granulomatous inflammation by IFN-gamma producing TH1 cells 3. Defective regulatory T cell function: FoxP3 and IL-2 deficiencies result in inflammatory bowel disease 4. defective autophagy

Question 29

hx: 12 month old, irritability and lack of normal growth, underweight, pale appearance, protuberant abdomen, mild dehydration, muscle wasting, no enlargemtn of spleen, liver, lymph nodes. Hgb is low due to not absorbing Fe from the gut. Positive Ab's for IgA and IgG. Biopsy shows total villous atrophy and increased intraepithelial lymphocytes on second portion of duodenum and duodenal bulb

Answer 29

Celiac disease - embeded within epithelial lining there are an invasion of lympochytes within the epithelial surface - an immune mediated disease mediated by T cells - estimated frequency of 1:100 - associated with other AI diseases - abdominal pain, diarrhea, anemia, growht failure, osteoporosis

Question 30

what does celiac occur?

Answer 30

- response against gluten taken up in the gut that is deaminated and presented to B cells and T cells. - the T cells are activated against gluten and are responsible for the tissue damage

Question 31

Hx: food allergy after eating a peanut butter cookie. Was introduced to peanuts one month earlier. labored breathing, low BP, results in anaphylactic shock.

Answer 31

- food allergy: a Type I hypersensitivity - IgE mediated usually (present in young children) - non IgE are eosinophilic in origin (chronic skin/GI symptoms) Childhood food allergies: thought that mucosal barrier is not complete around 4 years of age. Affects GI and skin.