Chapter 5: Secondary Lymphoid Tissue: Innate Immune Response Meets Adaptive Flashcards
What chemokine receptor will activated dendritic cells begin to express?
CCR7
CCR7 receptors on dendritic cells are activated by chemokines produced by what cells?
endothelial cells
Where are DCs primarily found in the lymph node?
paracortex
Explain migration of APCs to secondary lymphoid tissue.
- DCs and phagocytes bind to ag via PRRs (TLRs etc)
- Activation of TLRs induces acute inflammatory response > production of pro-inflammatory cytokines
- Cytokines cause change in phenotype altering migration pattern and enhancing function
- activated dendritic cells express chemokine receptor called CCR7 which is activated by chemokines that are produced by the endothelium
- Chemokines bind to CCR7 on DCs, allowing them to exit tissue,
- Upon activation DCs switch focus from antigen capture to ag presentation
- activated DCs concentrate in draining lymph nodes and become trapped in paracortex
- Naive T cells expressing CCR7 bind to chemokines on HEVs (high endothelilal venules) and migrate to the paracortex
What are the sites in the body in which naive, mature lymphocytes will first be exposed to their specific antigens?
lymph nodes and spleen
Macrophages are typically found in what part of the lymph node?
throughout
PALS in spleen stands for what? Describe it.
periarteriolar lymphoid sheaths PALS which has mostly T cells
arterioles in the spleen which become surrounded by cuffs of lymphocytes
Label this picture.
What are other ways B7 CD marker is designated?
B7.2 or CD86
DCs constitutively express what co-stimulatory molecules?
B7 (B7.2), CD40
What are some inducible co-stimulatory molecules found on DCs?
IFN-y, TLRs
Macrophages have constitutive expression of what co-stimulatory molecules?
B7 (B7.2), CD40
Macrophages induce which co-stimulatory molecules?
IFN-y, TLRs
B cells express what constitutive co-stimulatory molecues?
CD 40
B cells express what inducible co-stimulatory molecules?
T cells, B7
Describe expression of HLA class II in DCs.
constitutive but upregulated by IFN-y
Describe expression of HLA class II from macrophages?
negative or low level expression but induced by IFN-y
Describe expression of HLA Class II from B cells?
constitutive but upregulated by IL-4
What is the major function of DCs?
activation of naive Th cells
Major function of macrophages?
initiation and effector phase of the Th1 response for cell mediated immunity
Major function of B cells?
initiation of the Th2 response for humoral immunity
Describe the exogenous pathway of antigen presentation.
- MHC II molecules produced in ER of APC and Ii (invariant chain) produced at same time
- Ii has a class II invariant chain peptide (CLIP) that binds with high affinity to peptide binding cleft of newly synthesized MHC class II
- CLIP + Ii transported to location of endocytic vesicles with ingested ag
- 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
Describe endogenous pathway of MHC loading.
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
What bridges the TAP transporter to the MHC class I molecules?
tapasin
MOA by which proteasome inhibitors act in the treatment of cancer.
regulatory proteins like p53 are not degraded in proteasome so they can induce apoptosis
Name 2 proteosome inhibitors discussed in this chapter.
bortezomib
carfilzomib
What is the use for bortezomib?
currently approved to treat multiple myeloma and mantle cell lymphoma (clinical trials for leukemia)
What is the use for carfilzomib?
currently approved to treat multiple myeloma (clinical trials for leukemia and lymphomas)
Cross presentation (cross priming) meaning?
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
