Lecture 13: GI Immunology (Grosche)

Question 1

fxs of the mucosal immune system

Answer 1

1) maintains immunological homeostasis along the epithelial surface in oral/nasal/respiratory/GI/urogenital cavities and tracts
2) mediates symbiotic relationship b/w host and endogenous microorganism
3) first line of physical and immunological defense against invading pathogens

Question 2

MALT

Answer 2

mucosa-associated lymphoid tissue

Question 3

NALT

Answer 3

nasopharynx-assoc. lymphoid tissue

Question 4

BALT

Answer 4

bronchus-assoc. lymphoid tissue

Question 5

GALT

Answer 5

gut-associated lymphoid tissue

Question 6

inductive site

Answer 6

regional MALT and follicle-associated epithelium containing microfold (M) cells. (M cells transport organisms and particles from the gut lumen to immune cells across the epithelial barrier, and thus are important in stimulating mucosal immunity)

Question 7

3 examples of antigen-presenting cells. What do they do?

Answer 7

dendritic cells, macrophages, B cells. Prime naive B and T cells to become effector cells

Question 8

what is the largest lymphoid organ in the body?

Answer 8

the gut

Question 9

major fxs of the GI tract

Answer 9

1) digestion/absorption of nutrients
2) barrier function
3) immune response

Question 10

Components of mucosal defense mechs.

Answer 10

• extramucosal components
• intact mucus epithelium
• subepithelial/submucosal microcirculation and nervous system
• mucosal immune system
• ability of mucosa to undergo repair

Question 11

extramucosal components of mucosal defense mechanisms

Answer 11

• saliva
• HCl
• digestive enzymes
• water and electrolytes
• mucus
• immunoglobins
• normal peristalsis
• normal commensal microflora

Question 12

indigenous gut flora include 2 groups:

Answer 12

autochthonous (those with an evolutionary symbiotic relationship) and allochthonous flora (those with some pathogenic potential)

Question 13

non-indigenous gut flora include:

Answer 13

environmental flora (non-gut organisms acquired from the environment)

Question 14

what part of the gut are gram neg. and anaerobic bacteria more commonly found?

Answer 14

distal GI tract (past ileum)

Question 15

protective fxs of normal gut flora

Answer 15

• pathogen displacement
• nutrient competition
• production of anti-microbial factors to attack pathogens

Question 16

metabolic fxs of normal gut flora

Answer 16

• control of epithelial cell differentiation and proliferation
• synthesis of vitamins
• fermentation of non-digestible digestible dietary residues and mucus
• ion absorption
• salvage of energy
• production of by-products

Question 17

structural fxs of normal gut flora

Answer 17

• barrier fortification
• induction of IgA
• tightening of tight junctions
• immune system development

Question 18

Where are Peyer’s patches located?

Answer 18

small intestine

Question 19

where are lymphoid follicles located?

Answer 19

throughout entire gut

Question 20

Describe the structure and function of a Peyer’s patch

Answer 20

Domes of tissue covered by an epithelial layer and M cells. M cells come into contact with luminal antigens and transport them to antigen-presenting cells. T cells, B-cells and memory cells are stimulated upon encountering antigen. These cells then pass to the mesenteric lymph nodes where the immune response is amplified. Activated lymphocytes pass into the blood stream and travel to the gut where they carry out their final effector functions.

Question 21

describe structure of the mucosal epithelium

Answer 21

• monolayer of intestinal epithelial cells
• apical junction complex
• overlaying mucus layer

Question 22

what do goblet cells produce? What is its function?

Answer 22

mucus. Acts as physical barrier/bacterial adhesion/antibacterial substance

Question 23

main regulators of adaptive immunity

Answer 23

epithelial cells

Question 24

How do intestinal epi. cells effect innate immunity?

Answer 24

they maintain the density of apical microorganisms (antimicrobial peptides, neutrophils)

Question 25

3 components of the intestinal epithelial cell physical barrier

Answer 25

• microvilli of brush border
• tight junctions
• glycocalyx and thick mucus layer

Question 26

compare the responsiveness to bacteria at the luminal surface of intestinal epithelial cells to the crypts in the epithelium

Answer 26

Low responsiveness at the luminal surface to commensal bacteria. However, the crypts must be kept sterile to protect the stem cells that reside there. The crypts have special receptors (paneth cells) that recognize microbes and activate a pro-inflammatory mechanism if bacteria invade

Question 27

transcellular vs. paracellular pathways through the intestinal epithelial barrier

Answer 27

transcellular: pathway for molecules to move directly across the epithelial cells; mediated with receptors and channels. (90%)
paracellular: substances move across barrier BETWEEN cells through tight junctions and adherens junctions. (10%)

Question 28

ileal transport of IgG in neonates

Answer 28

used for uptake of immunoglobulins from collostrum during the first 24hrs of life. IgG binds to Fc receptors on apical membrane and is transported to basolateral membrane via endocytosis

Question 29

What is the apical junction complex?

Answer 29

controls paracellular pathway via tight junctions and adherens junctions. Regulates permeability of the GI tract

Question 30

fxs of adherens junctions

Answer 30

maintains cellular proximity and intercellular communication. Required for assembly of tight junctions

Question 31

fxs of tight junctions

Answer 31

• hold cell together
• maintain cell polarity
• regulate paracellular permeability

Question 32

immune cells of the lamina propria of the mucosal immune system

Answer 32

• plasma cells
• T and B cells
• Dendritic cells
• Macrophages
• mast cells

Question 33

immune cells of the epithelium of the mucosal immune system

Answer 33

effector T cells

Question 34

the main immunoglobulin of the GI tract

Answer 34

IgA

Question 35

functions of secretory IgA

Answer 35

• binds pathogens/toxins
• neutralizes intracellular LPS
• exports pathogens/toxins to apical surface
• limits access of pathogens to mucosal surfaces w/o risking inflammatory damage

Question 36

how does the nervous system regulate mucosal immunity?

Answer 36

modulation via sympathetic, parasympathetic, and local peripheral nervous system. Transmitters, hormones, and receptors all help modulate a normal immune response (i.e. neuroendocrine hormones regulate cytokine balance)

Question 37

Mechanisms of intestinal tolerance to commensal bacteria

Answer 37

• bacteria have impaired ability to escape mucus/invade epithelial barrier, low endotoxicity, and they inhibit the inflammatory pathway
• mucosal epithelium has reduced expression of receptors and permanent activation of anti-inflammatory response
• lamina propria has tolerogenic dendritic cells macrophages, and T cells, and produces anti-inflammatory cytokines

Question 38

Response of mucosal immune system to pathogens

Answer 38

• recognition by complement, NK cells
• inflammatory response
• activation of adaptive immune system
• destruction of pathogens + immunity

Question 39

failure to eradiate pathogens or to discriminate self from non-self leads to:

Answer 39

pathogen proliferation (sepsis), autoimmunity and allergy

Question 40

How is inflammation resolved?

Answer 40

• neutrophil infiltration stopped
• uptake and clearance of apoptotic cells and microorganisms
• antimicrobial activity of mucosal epithelial cells stimulated
• switch to biosynthesis of anti-inflammatory and pro-resolution lipid mediators (lipoxins, resolvins, protectins)

Question 41

Process of mucosal restitution and repair

Answer 41

• villus contraction
• restitution (migration of epithelial cells to seal exposed membrane)
• closure of leaky intercellular spaces (tight junctions)
• initiated by mediators released from nerves, immune effector cells, myofibroblasts, endothelial cells, extracellular matrix
• “repair” occurs after “restitution”