W2L3 - Dendritic Cells Flashcards
How are T Cells primed?
Antigen presentation essential for the generation of T cell responses
Priming occurs in secondary lymphoid organs = spleen and LN
Must occur in T cell zones
Major histocompatibility complex (MHC) proteins present Ag to T cells
Class 1 & 2 MHC Proteins
Class I MHC proteins: - found on virtually all body cells - present antigen to CD8+ T cells Class II MHC proteins: - found only on certain cell types - professional antigen presenting cells - present antigen to CD4+ T cells
Dendritic Cells
Key in both innate and adaptive immune responses
Immature and mature forms
Involved in antigen presentation to T cells
Tolerance and Signals
Signal 1 = peptide in MHC class I or class II molecules Signal 2 = co-stimulatory molecule-ligand binding Signal 3 = cytokines => polarise cells
Dendritic Cell:T Cell Contact Time and Signal Strength
Resting DC - low Ag - no costimulation - short contacts Active DC - high Ag - high costimulation - cytokines - long contacts Exhausted DC - high Ag - high costimulation - short contacts
Types of Professional APCs
Dendritic cell - location in lymph node: T-cell areas Macrophage - location in lymph node: everywhere B Cell - location in lymph node: follicles
Cytosolic Pathogens, Intravesicular Pathogens & Extracellular Pathogens
Cytosolic - degraded in: cytosol - peptides bind to: MHC class 1 - presented to: CD8 T cells Intravesicular and extracellular - degraded in: endocytic vesicles (low pH) - peptides bind to: MHC class 2 - presented to: CD4 T cells
Differences between Professional APCs - Antigen Uptake
DCs - macropinocytosis - phagocytosis - viral infection Macrophages - phagocytosis B cells - Ag-specific receptor (Ig)
Differences between Professional APCs - MHC Expression
DCs - low on tissue DCs - high on DCs in lymphoid tissue Macrophages - inducible by bacteria and cytokines B cells - constitutive - increases on activation
Differences between Professional APCs - Co-Stimulatory Delivery
DCs - constitutive by mature, nonphagocytic lymphoid DCs Macrophages - inducible B cells - inducible
Differences between Professional APCs - Antigen Presented
DCs - peptides - viral antigens - allergens Macrophages - specific antigens - intracellular and extracellular pathogens B cells - soluble antigens - toxins - viruses
Differences between Professional APCs - Location
DCs - ubiquitous throughout body Macrophages - lymphoid tissue - connective tissue - body cavities B cells - lymphoid tissue - peripheral blood
Danger Signals
Drive DC activation
Through pattern recognition receptors (PRRs)
Activate DCs
PRRs recognise pathogen components given off by antigen
- e.g. PAMPs
PRRs recognise endogenous alarmins given off by antigen
- e.g. DAMPs
If the DC recognises the alarmins (PAMPs, DAMPs etc.):
- release inflammatory cytokines
- upregulate MHC class I and MHC class II
- upregulate co-stimulatory molecules
Why are DCs best at priming T cells?
DCs continuously sample their surroundings - ingest antigens
DCs travel to LN and spleen (right place)
Mature DCs 100x more potent than other APC in stimulating resting T cells
Express high levels of costimulatory molecules
Expression of MHC-peptide complexes 10-100x on DC than other APC
Express high levels of IL-12 upon maturation
Cluster naive T cells
Interact with many T cells at once
Allows T cells to ‘sample’ MHC-peptide complexes on DC surface to find specific MHC-peptide complexes that it recognises
Cancer Immunity
- Capture and presentation of tumour associated antigen (TAA) by APCs and DCs
- DC activation by danger signals
- Activated DCs carry TAAs to lymph node
- upregulate costimulatory molecules - TAA presented to CD4+/CD8+ T cells
- Stimulated CD4+ cells express CD40L, further stimulating CD40-expressing DCs
- TAA-specific activated effector cells migrate to tumour (CD4+/CD8+)
- Migrated T cells attack tumour cells
