Chapter 5: Secondary Lymphoid Tissue: Innate Immune Response Meets Adaptive

Question 1

What chemokine receptor will activated dendritic cells begin to express?

Answer 1

CCR7

Question 2

CCR7 receptors on dendritic cells are activated by chemokines produced by what cells?

Answer 2

endothelial cells

Question 3

Where are DCs primarily found in the lymph node?

Answer 3

paracortex

Question 4

Explain migration of APCs to secondary lymphoid tissue.

Answer 4

1. DCs and phagocytes bind to ag via PRRs (TLRs etc)
2. Activation of TLRs induces acute inflammatory response > production of pro-inflammatory cytokines
3. Cytokines cause change in phenotype altering migration pattern and enhancing function
4. activated dendritic cells express chemokine receptor called CCR7 which is activated by chemokines that are produced by the endothelium
5. Chemokines bind to CCR7 on DCs, allowing them to exit tissue,
6. Upon activation DCs switch focus from antigen capture to ag presentation
7. activated DCs concentrate in draining lymph nodes and become trapped in paracortex
8. Naive T cells expressing CCR7 bind to chemokines on HEVs (high endothelilal venules) and migrate to the paracortex

Question 5

What are the sites in the body in which naive, mature lymphocytes will first be exposed to their specific antigens?

Answer 5

lymph nodes and spleen

Question 6

Macrophages are typically found in what part of the lymph node?

Answer 6

throughout

Question 7

PALS in spleen stands for what? Describe it.

Answer 7

periarteriolar lymphoid sheaths PALS which has mostly T cells

arterioles in the spleen which become surrounded by cuffs of lymphocytes

Question 8

Label this picture.

Answer 8

Question 9

What are other ways B7 CD marker is designated?

Answer 9

B7.2 or CD86

Question 10

DCs constitutively express what co-stimulatory molecules?

Answer 10

B7 (B7.2), CD40

Question 11

What are some inducible co-stimulatory molecules found on DCs?

Answer 11

IFN-y, TLRs

Question 12

Macrophages have constitutive expression of what co-stimulatory molecules?

Answer 12

B7 (B7.2), CD40

Question 13

Macrophages induce which co-stimulatory molecules?

Answer 13

IFN-y, TLRs

Question 14

B cells express what constitutive co-stimulatory molecues?

Answer 14

CD 40

Question 15

B cells express what inducible co-stimulatory molecules?

Answer 15

T cells, B7

Question 16

Describe expression of HLA class II in DCs.

Answer 16

constitutive but upregulated by IFN-y

Question 17

Describe expression of HLA class II from macrophages?

Answer 17

negative or low level expression but induced by IFN-y

Question 18

Describe expression of HLA Class II from B cells?

Answer 18

constitutive but upregulated by IL-4

Question 19

What is the major function of DCs?

Answer 19

activation of naive Th cells

Question 20

Major function of macrophages?

Answer 20

initiation and effector phase of the Th1 response for cell mediated immunity

Question 21

Major function of B cells?

Answer 21

initiation of the Th2 response for humoral immunity

Question 22

Describe the exogenous pathway of antigen presentation.

Answer 22

1. MHC II molecules produced in ER of APC and Ii (invariant chain) produced at same time
2. Ii has a class II invariant chain peptide (CLIP) that binds with high affinity to peptide binding cleft of newly synthesized MHC class II
3. CLIP + Ii transported to location of endocytic vesicles with ingested ag
4. HLA DM is found in late endosome and exchange CLIP for phagocytosed peptide that binds to MHC II molecule with higher affinity than the CLIP

Question 23

Describe endogenous pathway of MHC loading.

Answer 23

peptides from proteins are transported through a peptide transporter known as TAP complex (transporter of antigen processing) and into ER where they bind to MHC class I molecules

Question 24

What bridges the TAP transporter to the MHC class I molecules?

Answer 24

tapasin

Question 25

MOA by which proteasome inhibitors act in the treatment of cancer.

Answer 25

regulatory proteins like p53 are not degraded in proteasome so they can induce apoptosis

Question 26

Name 2 proteosome inhibitors discussed in this chapter.

Answer 26

bortezomib
carfilzomib

Question 27

What is the use for bortezomib?

Answer 27

currently approved to treat multiple myeloma and mantle cell lymphoma (clinical trials for leukemia)

Question 28

What is the use for carfilzomib?

Answer 28

currently approved to treat multiple myeloma (clinical trials for leukemia and lymphomas)

Question 29

Cross presentation (cross priming) meaning?

Answer 29

When APC like DC can ingest a virally infected MHC class I cell and present viral ag to CD8 T cells as well as CD4 T cells