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IMMU3201 L4

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http://www.news-medical.net/health/What-are-Dendritic-Cells.aspx
http://www.news-medical.net/health/Types-of-Dendritic-Cells.aspx
http://www.news-medical.net/health/Dendritic-Cell-Life-Cycle.aspx
http://www.news-medical.net/health/Dendritic-Cells-and-Cytokines.aspx
http://www.news-medical.net/health/Dendritic-Cells-and-HIV.aspx


The discovery and definition of Dendritic Cells
- Dendritic cells are epidermal langerhans cells

What are the 3 dendritic cell subsets?
1. Plasmacytoid DC
2. Myeloid DC
3. Gap DC


Plasmacytoid Dendritic Cell (pDCs)
- Plasmacytoid DC express surface markers CD123, CD303 and CD304
- They do NOT express high levels of CD11 or CD14 distinguishes them from
conventional dendritic cells
- They express Toll-like receptors, TLR-7, TLR-9
- TLR-7 detect ssRNA
- TLR-9 detects CPG DNA
- Upon stimulation, Plasmacytoid DC produce Type-1 IFN (IFN-, IFN-) which are
anti-viral compounds
- Number of pDCs decrease during chronic HIV infection




Myeloid Dendritic Cells (mDCs)
- Myeloid DCs are most similar to monocytes
- mDC are made up of at least two subsets: mDC-1, mDC-2
- mDC-1 are common and is a major stimulator of T cells
- mDC-2 are rare and have a function in fighting wound infection
- Myeloid dendritic cells secrete IL-12, which is involved in differentiation of nave T
cells into Th1 cells
- Myeloid dendritic cells express Toll-like Receptors: TLR-2 and TLR-4


Gap Dendritic Cells
- wtf


How are dendritic cells made? DC haematopoiesis and Differentiation
- Dendritic cells are derived from hematopoietic bone marrow progenitor cells
- Progenitor cells transform into immature dendritic cells
- Immature cells sample surrounding environment for pathogens via Pattern
Recognition Receptors (PRRs) such as Toll-like receptors (TLRs)
o TLRs recognise specific chemical signatures on subsets of pathogens
- Immature dendritic cells activate upon contact with antigen to become mature
dendritic cells
o Immature DCs phagocytose pathogens and degrade their protein into
peptides to be presented on their surface in association with MHC molecules
- Mature DCs upregulate co-receptors CD80, CD86, CD40, which are involved in T-cell
activation
- Mature dendritic cells migrate to the lymph node via lymphatic system after
upregulation of chemokine, CCR7
- Mature dendritic cells can also migrate to spleen via blood stream



Dendritic cell subsets and Migration
- CD11 migration from bone marrow out
- CD123 migrate to spleen

DC in gut
Dendritic cells (DCs) are specialized antigen-presenting cells that orchestrate innate and
adaptive immune responses. The intestinal mucosa contains numerous DCs that are highly
specialized in function. Mucosal DCs display a unique response to toll-like receptor ligands,
are capable of driving immunoglobulin isotype switching to IgA, can imprint gut-homing
receptors on T and B cells, and drive either T regulatory or Th17 cells depending on the
analysed subtype.

DC antigen receptors and antigen processing
- DC antigen receptors
- DC antigen processing
- DC activation (stimulatory or alternative/regulatory)
DC MHC antigen presentation
DC co-stimulation
DC cytokine release
DC chemokine release

Receptors on dendritic cell
- Surface TLR
o TLR-1/2 lipoprotein
o TLR-2/6 lipoprotein
o TLR-4 lipopolysaccharides
o TLR5 flagellin
- Endosomal TLR
o TLR-3 dsRNA
o TLR-7 - ssRNA
o TLR-9 CpG DNA
- NLR
o NOD-1 bacterial peptidoglycans
- CLR
o
- RLH
o ROG-1 short ds RNA
o MDAS long ds RNA


DC migration
- DC precursors migrate from marrow to blood
- They migrate into non-haematopoietic tissue
- DC subpopulation migrates from the skin
- DC migrate within lymph nodes

DC interaction
- DC and NK cells
- DC and CD4 T cells
- DC and CD8 T cells
- DC and Treg cells
- DC and B cells


DC-T cell Differentiation

DC in human disease
- DC in Infection
- Viruses
- Bacteria
- Fungi
- Protozoa
- Helminth
- DC in Cancer
- Failed DC responses
- DC amplification of immune suppression

DC are central to HIV infection

DC based therapies
- DC used for Immune stimulation (vaccination)
o Infections, cancer
- DC used for immune suppression
o Transplantation, Autoimmune/inflammatory disease

Dendritic cell vaccination
- Take out dendritic cell
- Load them with cancer antigen targets
- Put DC back into patient via injection
- DC migrate to lymph node to activate CTL that is specific for that antigen

What are Therapeutic DC vaccination are used for?
- Acute myeloid leukaemia
- Multiple myeloma
- Other cancers

DC used for immunosuppression
- To suppress Grave vs Host disease (where donor reject recipient)

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