Term
| Provide a general outline of DC activation and migration |
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Definition
1) Capture and process antigens in the periphery
2) Become activated and migrate to draining lymph nodes where they present antigen to naive T-cells.
3) CD4+ T cells secrete cytokines that activate macrophages leading to destruction of microbes (if MHC II) and CD8+ T cells kill antigen-expressing infected cells (if MHC I). |
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Term
| Classify DCs in terms of basic morphology, tissue distribution and origins. |
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Definition
1) large cells with dendrite-like extensions for antigen uptake and cell:cell contact
2) Almost everywhere except in the CNS, eye and testes (immune privileged sites)
3) Arise from hematopoetic CD34+ cells, and both myeloid (CMP) and lymphoid progenitors (CLP)
4) All DCs express HLA-DR (MHC-class II), but are VERY HETEROGENEOUS and must be classified by surface phenotype AND function. |
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Term
| What are the primary functions of DCs? |
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Definition
SHORT- detect danger, capture antigens and bring them to naive T-cells, stimulate T and B cells and secrete cytokines.
1) Detect danger signals (foreign or self)- detect PAMPS through PRRs
2) Capture antigens
3) Migrate, and carry antigens to periphery to site of naive T cells (lymph nodes and spleen)
4) Stimulate naive T and B cells after cross presentation (forming immunological synapses through MHC-I and MHC-2-mediated interactions
5) Secrete cytokines |
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Term
| Explain how and why DCs have become targets for rational vaccine design (explain Preventative Vaccines and Therapeutic Vaccines) |
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Definition
They play a pivotal role in initiating immune responses.
1) Preventative Vaccines are used against infections and stimulate primary immune response to infectious agents which leads to memory response (give antigens with adjuvant molecules to target DCs)
2) Therapeutic Vaccines require modulation or re-programming of established memory responses- important for chronic infections and cancer |
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Term
| How do DCs detect danger signals (either foreign or self) in the microenviornment? |
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Definition
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Term
| How do DCs stimulate naive T-cells in the lymph nodes to differentiate and proliferate? |
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Definition
DC require co-stimulatory molecules (NEED B7)!
In the presence of a danger signal (i.e. an antigen), B7 on the DC will bind CD28 on the T-cell.
The CD will release IL-12, which will induce T-cell maturation, as well as autocrine release of IL-2. |
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Term
| Why might overactive B7 molecules be of clinical concern? |
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Definition
| If B7 acts as a co-stimulator at CD-T-Cell synapses in the presence of SELF-PEPTIDES, it could cause T cell proliferation and activation against the host, leading to autoimmune conditions. |
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Term
| What are the major physiological differences between immature and mature DCs in terms of their metabolic status? |
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Definition
DON"T SPOIL THE KIDS
1) Immature DCs eat a lot, but don't present many antigens
2) Mature DC's eat less and present the majority of antigens. |
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Term
| Distinguish between the TH1 and TH2 T-cell response pathways to DC activation. |
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Definition
1) TH1 involves viral, bacterial and autoimmune/transplant responses.
2) TH2 involves allergic, asthmatic and parasitic immune responses. |
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Term
| What is the basic lifestyle of a normal DC? |
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Definition
1) Arise in marrow and migrate as "DC precursors" to epithelium (in the case of Langerhans DCs).
2) In the presence of an antigen, DCs engulf the antigen and migrate to a lymph node, where they present the antigen to T-cells.
3) Effector T-cells leave the lymph nodes through efferent lymphatic ducts and travel through circulation to post-capillary venules
4) T-cells extravasate into the site of injury. |
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Term
| Explain the basic strategy of Ex-vivo/In-vivo DC vaccination to treat tumors. |
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Definition
1) Take DC precursors from bone marrow
2) Add cytokines to make immature DC's
3) Add pro-inflammatory cytokines and tumor antagonists (ex) anti-HER-2/neu)
4) Transplant mature DCs back into circulation and hope that they migrate to lymphoid tissues, and enter lymphatic circulation to target tumor. |
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Term
| What are some issues that need to be considered when developing DC-mediated tumor therapies? |
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Definition
Antigen type/deliver and DC type/maturation.
1) Method of antigen delivery (electroporation, viral, etc.)
2) Type of Dendritic cell to use (remember, HETEROGENEOUS)
3) State of Maturation of the DC
4) Type of antigen |
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Term
| How does phagocytosis occur in DCs and how can it be "enhanced"? |
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Definition
1) Attachment-recognition-ingestion-phagosome/lysosome fusion-digestion-release/recycling/presentation
2) IgG and C3b opsonization of targets for Fc and C3bR recognition on DC |
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Term
| Explain the process of antibody-mediated antigen processing in DCs. What about receptor-mediated endocytosis? |
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Definition
1) Antibodies form Ab-Ag aggregates that are taken up by Fc receptors on DCs
2) fMet-Leu-Phe bacterial sequence is recognized and endo/lysosomal fusion occurs. |
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Term
| How does antigen processing by Macropinocytosis occur in DCs? |
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Definition
| Soluble molecules can be taken in without receptors ("cellular drinking"). |
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Term
| How does antigen processing by Mannose and Scavenger receptors occur in DCs? |
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Definition
1) Mannose receptors form hexamers that must bind to multiple carbohydrate antigenic residues in order to initiate uptake (only bacteria have enough- self does not).
2) Scavenger receptors bind (-) charged species. |
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