Test 2: lecture 1 barriers

Question 1

___ are organized lymphoid structures in the small intestine that contain specialized mechanisms to sample the intestinal lumen. These mechanisms include M cells and specialized dendritic cells.

Answer 1

Peyer’s Patches

Question 2

Communication between ___ bacteria and the mucosal immune system is essential for normal mucosal immune functioning. The microbiota therefore plays an essential role in establishing and maintaining tissue homeostasis

Answer 2

commensal

Question 3

The ___immune system is directly exposed to the environment. Most pathogens invade through mucosal surfaces that in many cases forms a monolayer that is on epithelial cell thick and provides a verey large surface area for contact with foreign microbes.

Answer 3

mucosal

Question 4

___ is the major antibody isotype found in the intestinal lumen. It is secreted into the lumen by a specialized secretion mechanism involving the poly-Ig receptor

Answer 4

IgA

Question 5

____: specialized lymphocytes for surveillance of mucosal epithelial tissue

Answer 5

Intra-epithelial lymphocytes

Question 6

3 anatomical features of the mucosal immune system

Answer 6

mucosal epithelia close to lymphoid tissues

can be organized into compartments such as peyer’s patches or more diffuse

they have special ways to take up antigens - M cells in the peyer’s patch

Question 7

2 effector mechanisms of the mucosal immune system

Answer 7

even in the absence of infection there are activated/memory T cells

there are also “natural” effector/regulatory T cells present

Question 8

2 immunoregulatory things the mucosal immune system will do

Answer 8

decrease immune response to food and non-pathogen antigens

inhibitory macrophages and tolerance-inducing dendritic cells

Question 9

the mucosal immune system includes the :

Answer 9

epithelial layer

lamina propria

Question 10

what is in the lamina propria

Answer 10

Lamina Propria: the “space” under the epithelial cell layer: rich in connective tissue and contains abundant innate and adaptive immune cells
→ Lymphatic vessels collect fluids, antigens, pathogens

Question 11

secondary lymphoid organs in the mucosal tissues can be ___ or organized.

Answer 11

scattered

both filter lymph and connect to the mesenteric lymph nodes

Question 12

an example of organized lymphoid tissue is the __-

Answer 12

peyer’s patch in the GI tract

Question 13

M cells

Answer 13

found in the GI tract

part of the epithelial layer that separates the peyer’s patch from the gut lumen.

ruffled membrane→ no mucous secretion or surface glycocalyx

allows for uptake of pathogen

Question 14

how do M cells work

Answer 14

they will take up antigen (endocytic)

transcytosis in membrane bound vesicles

give pathogen to lymphoid cells- DC cells that carry the pathogen to peyer’s patch

Dendritic cells sample the material, become activated by PAMPs, activate T cells

Question 15

___ can extend processes across the epithelial layer of the GI tract to capture antigen from the lumen.

Answer 15

dendritic cells

Question 16

T cell priming and redistribution in the MALT

Answer 16

immature T cells with CCR7, LFA-1 and L-selectin enter lamina propria by HEV

they get activated by dendritic cells → drain via mesenteric lymph nodes → back into blood stream

activated T cells will express alpha4beta7 integrin and CCR9/CCR10 → this will pull activated T cells out of blood and back to the lamina propria

Question 17

immature T cells enter the peyer’s patch by ___

Answer 17

HEV (high endothelial venules)

Question 18

___ on immature T cells direct them to peyer’s patch

Answer 18

CCR7 and L-selectin

Question 19

T cells activated in the MALT are ___ with adhesion molecules that mediate distribution throughout the MALT

Answer 19

imprinted

alpha4:Beta7 integrin and CCR9

Question 20

naive T cells will have ___ receptor while activated T cells will have ___ recepetors

Answer 20

CCR7 (T zone) → CCR9/CCR10 (receptors for intestinal epithelial chemokines)

Question 21

naive T cells will have LFA-1 while activated T cells will have ___

Answer 21

alpha4:beta7 integrin → mucosal calling card

Question 22

gut homing effector T cells that express a4:B7 and L-selectin bind to ___

Answer 22

MAdCAM-1 on the endothelium of blood vessels in mucosal sites

Question 23

___ expressed on endothelium of blood vessels in all mucosal sites

Answer 23

MAdCAM-1

Question 24

gut epithelial cells express chemokines,____, specific for gut homing T cells

Answer 24

E-cadherin (on epithelial cells of mucosal surface) will attach to the alphaE:beta7

CCL25 and CCL28 will bind to the CCR10 and CCR9 receptors on the activated T cells

Question 25

Movement of IgA

Answer 25

made in the lamina propria by plasma cell will release **IgA** (dimer connected by a J chain) this attaches to **poly-Ig receptor** on the basal layer of the epithelial cell eats IgA and **transports it to the lumen** **IgA and part of the PIGR (secretory component)** is released into the lumen

Question 26

\_\_\_ binds to IgA on the basal side of epithelial cells in GI tract

Answer 26

poly-Ig receptor (PIGR)

Question 27

where does IgA work

Answer 27

can work in the lumen- binding and neutralizing pathogens and toxins can work inside the epithelial cell can work in the lamina propria and carry pathogens out to the lumen

Question 28

Lamina Propria lymphocytes: 3:1 ratio of \_\_\_T cells (just like LN, spleen). Mostly activated/memory cells.

Answer 28

CD4:CD8

Question 29

Intraepithelial lymphocytes (IELs): 90%\_\_\_\_, activated cells

Answer 29

T cells, mostly CD8s

Question 30

\_\_\_have direct contact with epithelial cells allows for close communication and rapid effector responses

Answer 30

IEL intraepithelial lymphocytes

Question 31

Type A IEL

Answer 31

conventional CD8+ T cells Effector CD8 T cells require **signal 1 only** **only needs to see antigen presented in MHC class 1** to trigger kill response will release perforin/granzyme and Fas-dependent pathway and kill target cell

Question 32

Type B IEL

Answer 32

T cells with limited TCR diversity detect stress signals: “induced self” Largely **MHC-peptide-independent** **NKG2D binds to MIC-A, B**: costimulation **CD8α:a** homodimers bind to a nonclassical MHC molecule called TL **epithelial cells will send out stress signal→ type B IEL will bind to MIC-A,B and TL and will kill cell**

Question 33

\_\_\_ receptors on the type B IEL will bind to TL on stressed epithelial cell and trigger kill response

Answer 33

CD8 alpha:alpha

Question 34

\_\_\_ receptors on the type B IEL will bind to MIC-A,B on stressed epithelial cell and trigger kill response

Answer 34

NKG2D

Question 35

when epithelia cells are stressed or damaged that produce ___ that can be seen by Type B IEL

Answer 35

MIC A and MIC B TL

Question 36

restitution of GI cells

Answer 36

when epithelial cells are killed neighboring cells will spread out and migrate to cover space -→ prevent pathogens from leaking through then they will divide

Question 37

oral tolerance

Answer 37

body will not react the same way to food as it does to an antigen mouse study- if you feed an antigen to a mouse, the mouse will become tolerant to that antigen( will not react), if you later inject that same antigen the mouse will not have an immune response

Question 38

commensal bacteria fill a ___ that function to prevent overgrowth of pathogenic bacteria

Answer 38

niche if good bacteria is there it prevents bad bacteria from entering that area -when things go wrong is when good bacteria is wiped out and bad bacteria can grow and attack

Question 39

how does the innate immune system tell the difference between commensal and pathogens?

Answer 39

location of where the pathogen is found good bacteria does not invade cells and would be seen by surface toll like receptors **where bad pathogens can break into the cell and would be seen by PRRs such as NOD2**

Question 40

Coincident detection of multiple PAMPs in distinct cellular locations may also allow the innate immune system to distinguish \_\_\_

Answer 40

pathogens from commensals. BOTH express PAMPs (MAMPs?) **ONLY pathogens invade**

Question 41

pathogens that invade the cell will trigger \_\_\_

Answer 41

TLR, NOD2 and activation of NFkB that triggers the release of cytokines that trigger the activation of the immune system

Question 42

DSS colitis

Answer 42

experimental model Chemical injury of colonic epithelium Breakdown of epithelial barrier Desequestration of commensals (leaky gut syndrome) **if you kill off commensal bacteria and TLR are the next line of defense. if animals do not have normal TLR they will die**