Lecture 38 GI

Question 1

what are the immune mechanisms that help protect from pathogen entry through the GI tract?

what type of barriers are these? physical, chemical barriers?

Answer 1

Goblet cells
Epithelial tight junctions
Commensal organisms
Intra-epithelial lymphocytes
GALT
M(microfold) cells

physical

Question 2

this physical barrier is produces mucus and glycocalyx as a physical barrier

Answer 2

Goblet cells

Question 3

this physical barrier is disrupted with GI inflammation

Answer 3

Epithelial tight junctions

Question 4

this physical barrier is >400 spp, compete for space and nutrients; antibiotics disrupt this homeostasis

Answer 4

Commensal organisms

Question 5

this physical barrier contains CD8, many have gamma-delta TCRs

Answer 5

Intra-epithelial lymphocytes

Question 6

this physical barrier contains B & T cells - Peyer’s patches (ileum)

Answer 6

GALT

Question 7

this physical barrier transports pathogens to APCs in the GALT

Answer 7

M (microfold) cells

Question 8

what are the chemical barriers produced from the mucosal surface?

Answer 8

secretory IgA
proteolytic enzymes
antimicrobial molecules

Question 9

this chemical barrier is produced in the Peyers patches and GALT and reduces pathogen adherence and neutralizes viruses, bacteria and toxins

Answer 9

Secretory IgA

Question 10

this chemical barrier is produced in the saliva, stomach and pancreas and breaks down proteins

Answer 10

proteolytic enzymes

Question 11

this chemical barrier is produced in the GI tract

Answer 11

antimicrobial molecules

Question 12

what are the examples of antimicrobial molecules?

Answer 12

lactoferrin
lysozyme
cathelicidins
defensins

Question 13

lactoferrin
lysozyme
cathelicidins
defensins

these are examples of?

Answer 13

antimicrobial molecules

Question 14

this antimicrobial binds iron to inhibit bacterial growth

Answer 14

lactoferrin

Question 15

this antimicrobial is produced by gastric, pyloric, duodenal glands as well as macrophages/monocytes; its also chemotactic and cleaves cell wall of Gram + bacteria

Answer 15

lysozyme

Question 16

this antimicrobial is formed in immune cells, in salivary glands, and in epithelia of respiratory, digestive and reproductive tracts; antimicrobial

Answer 16

cathelicidins

Question 17

this antimicrobial is 30-40 aa peptides produced by granulocytes, epithelial cells, and Paneth cells

its Functions: chemotactic, disrupt bacterial & fungi cell membranes & cause cell lysis

Answer 17

defensins

Question 18

Celiac disease, IBD-Crohns and Ulcerative colitis are what types of diseases?

Answer 18

GI diseases

Question 19

that are the types of GI diseases discussed in class?

Answer 19

Celiac disease and IBD-Crohns, IBD-Ulcerative colitis

Question 20

what are the anti-inflammatory cytokines of the gut?

Answer 20

IL-10, TGF-beta

Question 21

what are the local dendritic cells that live in the GI tract interacting with T cells called? what does this do?

Answer 21

CD103+CD11b+; this causes differentiation of naive T lymphs into Tregs in response to microbial antigens

Question 22

these cytokines dampen the immune response?

Answer 22

Tregs and TGF-beta

Question 23

This IL is produced by local DCs and Th2 cells to decrease proinflammatory cytokine production?

Answer 23

IL-10

Question 24

what causes the ankle swelling in Celiac disease?

Answer 24

albumin deficiency

Question 25

differential diagnosis for celiac disease?

Answer 25

``` celiac disease milk intolerance common variable immunodeficiency disease IgA deficiency HIV infection ```

Question 26

what lab tests det malabsorption for celiac disease?

Answer 26

low bicarb low Ca2+, low vitamin D low albumin

Question 27

what is the acute cause of malabsorption? if gradual and progressive weight loss? this is for celiac disease?

Answer 27

infection; defective digestion and flattening of the intestinal villi

Question 28

what is the leading diagnosis for Celiac disease?

Answer 28

gluten intolerance, wheat, barley, rye

Question 29

General manifestations of gluten sensitivity?

Answer 29

active GI symptoms silent/subtle latent dermatitis herpitiformis celiac disease not diagnosed til 3rd or 4th decade of life

Question 30

what are the diagnostic tests for celiac disease?

Answer 30

humoral and cell mediated problem, IELs cause villous atrophy then you have to keep in mind the transglutaminase 2a antibodies and antigliadin antibodies *keep in mind how these function

Question 31

significant histological findings of the mucosal surface on the duodenum in celiac disease?

Answer 31

broad and short intestinal villi

Question 32

what is the main pathogenesis of Celiac disease? describe what activates this

Answer 32

cytotoxic T cells (IELS) leads to villous atrophy IFNg releases IL-15 which causes IELs to become cytotoxic then there is IL-21 which continues the inflammation response both have a suppressive effect on Tregs

Question 33

this diagnostic tool is used to classify Celiac disease?

Answer 33

Marsh Classification

Question 34

main treatment for celiac disease?

Answer 34

removal of gluten from diet *TG2a antibodies, IL-15 inhibitors, gliadin peptide specific T cell response

Question 35

How is GI mucosal inflammation controlled?

Answer 35

IL-10 and TGF-beta

Question 36

what is the pathogenesis of IBD? so because we know this is due to impaired barrier function, what factors initiate this? what inflammatory cells are involved?

Answer 36

lack of Treg Control and decreased T cell apoptosis multifactorial; macrophages, T cells (helper T cells and Th17s), innate lymphoid cells these cells respond to microbial antigens and ones that produce cytokines promoting chronic inflammation

Question 37

what anti-inflammatory DCs promote Treg differentiation and anti inflammatory cytokine production in IBD? what happens when another set of DCs come into the area when a pathogen invades?what is this called?

Answer 37

CD103+CD11b+ migration into the intestine from the blood and immunogenicity results CD103-CD11b+

Question 38

what immunogenic APCs produce IL-1beta, IL-6, 12, 18, 23, TNF-alpha these in turn activate?

Answer 38

CD103-CD11b+ ILCs (IFN-g, IL-17, IL-22 and T cells 1,2, 17)

Question 39

what are the major symptoms of IBD?

Answer 39

chronic inflammation(leads to cancer risk due to upregulation of IL-22), fibrosis, and epithelial damage

Question 40

what are the major signs and symptoms of Crohn's disease?

Answer 40

deep granulomas cobblestoning garden hose string sign

Question 41

where does crohn's disease occur?

Answer 41

terminal ileum

Question 42

what two proteins are diagnostic in IBD? polymorphism?

Answer 42

OmpC and ASCA NOD2 polymorphism

Question 43

pathophysiology of crohn's?

Answer 43

IL-2/IL-10 deficiency Environmental agent Mutation of NOD2 leading to a gain of function, excessive release of Th1/Th17

Question 44

what is the significance of the NOD2 gene?

Answer 44

it codes for a protein that senses muramyl dipeptide that initiatas the NF-KB pathway, but when mutated they hyper-respond resulting in excessive inflammation and do not shut off

Question 45

where does Ulcerative Colitis occur?

Answer 45

colon and rectum

Question 46

what are the major presenting s/s of ulcerative colitis?

Answer 46

bloody diarrhea, inflammation, P-ANCA (pericytoplasmic anti-neutrophil cytoplasmic antibody)

Question 47

what is the pathophysiology of Ulcerative Colitis?

Answer 47

not driven by Th1 cytokines, its driven by NKT cells stimulated by IL-13

Question 48

what is the pathophysiology of Ulcerative Colitis?

Answer 48

not driven by Th1 cytokines, its driven by NKT cells stimulated by IL-13

Question 49

what cytokines are elevated in ulcerative colitis?

Answer 49

IL-5 and IL-13 (fibrosis and disruption of epithelium)

Question 50

what cytokines are elevated in Crohn's disease?

Answer 50

IFN-gamma (activation of macrophages, inflammatory cells)

Question 51

what is the best way to manage IBD?

Answer 51

anti-TNF, anti-IL-12, anti-IL-23

Question 52

how do we treat Crohn's specifically?

Answer 52

``` Anti-TNF corticosteroids antibiotics nutritional deficiencies monitor for cancer ```

Question 53

how do we treat UC specifically?

Answer 53

similar approach monitor for toxic megacolon monitor for colonic carcinoma