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Infection and Immunity > Dendritic cells > Flashcards

Dendritic cells Flashcards

1
Q

What is the primary function of dendritic cells?

A

Capture and presentation of protein antigens to naive T cells

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2
Q

What are the 2 major functions of APCs?

A

Capture and process antigens for presentation to T cells
Produce signals required for proliferation and differentiation of lymphocytes

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3
Q

Why are DCs unique?

A

They are the only cells with the ability to present antigens to naive T cells and induce primary immune responses

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4
Q

What are DCs generated from?

A

HSCs in the bone marrow

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5
Q

How do DCs differentiate?

A

Under the control of a complex network of soluble growth factors produced by BM stroma and direct cell-cell contact with BM stromal cells
e.g. GM-CSF, IL-3, FLT3L

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6
Q

What do DCs give rise to?

A

Circulating precursors that remain in tissues where they reside as immature cells

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7
Q

Where are immature DCs found?

A

Widely distributed in all tissues - particularly those which interface the environment
Located throughout epithelium of skin, respiratory tract and GI tract

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8
Q

Where are immature DCs recruited to?

A

Sites of inflammation in peripheral tissue by chemokines (CCL20, CCL5, CCL3)

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9
Q

What chemokine receptors do immature DCs express?

A

CCR1
CCR2
CCR5
CCR6
CXCR1

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10
Q

What are immature DCs efficient at?

A

Antigen capture

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11
Q

What does antigenic material include?

A

Apoptotic bodies
Bacterial material
Material from virally infected cells
Hsp/antigen complexes
Immunoglobulin cross-linked material
Extracellular fluid
Material from healthy cells

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12
Q

What is receptor mediated endocytosis?

A

Antigen will bind to specific receptors on DC surface and become internalised in clathrin-coated vesicles or clathrin-uncoated vesicles
C-type lectin receptors e.g. mannose receptor, CEX-205
Fc-gamma receptor types I (CD64) and II (CD32)
CD91 alpha2-macroglobulin receptor (hsp)

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13
Q

What is phagocytosis of particulate material?

A

Apoptotic and necrotic cell fragments
Bacteria inc. mycobacteria
Intracellular parasite such as Leishmania major
Viruses
Latex beads

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14
Q

What is macropinocytosis?

A

Internalisation of antigens into macropinosomes - actin dependent process that requires stimulation for growth factors e.g. colony stimulating factor (CSF-1, epidermal growth factor (EGF) or platelet derived growth factor (PDGF)
Antigens processed and loaded onto MHC molecules of DCs
Aquaporins may be responsible for constitutive macropinocytosis

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15
Q

How do immature DCs become mature?

A

Must receive maturation stimulus to trigger transition from immature antigen capturing cells to mature antigen presenting cells

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16
Q

What are the maturation stimuli?

A

Pathogenic molecules due to infection - LPS, bacterial DNA, dsRNA
Balance between pro and anti-inflammatory signal in local environment
T cell derived signals - CD40L

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17
Q

What happens upon maturation of DCs?

A

Down regulation of receptors for inflammatory chemokines - loss of endocytic and phagocytic receptors
Down regulation of antigen capture
Change in morphology
Upreg of receptors for homing to lymphoid tissue - CCR7
Upreg of antigen presentation
Upreg of co-stimulatory molecules - CD40, CD58, CD80, CD86

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18
Q

What changes in morphology occur upon maturation?

A

Loss of adhesive structures
Cytoskeleton remodelling
Acquisition of high cellular motility

19
Q

What regulates migration of DCs to lymphoid tissues?

A

Chemokine-chemokine receptor interactions

20
Q

What do DCs become responsive to upon maturation?

A

CCL19/MIP-3beta
CCL21/6Ckine

21
Q

Where is CCL19 expressed?

A

Afferent lymph ducts

22
Q

Where is CCL21 expressed?

A

High endothelial venules of lymph nodes
T cell areas of spleen and lymph nodes

23
Q

What do CCL19 and CCL21 do?

A

Guide DCs from tissue to T cell areas of lymph nodes

24
Q

What interactions occur in the lymph node?

A

Mature DCs migrate to T cell zones
Stimulation of quiescent, naive and mature T and B cells
Selection of rare CD4+ and CD8+ T cells and B cell clones
Induction of immune reaction by primary cytotoxic T cells and helper T cells

25
Q

What are the DC-T cell interactions?

A

DC-SIGN
Dectin-1
CD80 & CD86
CD40-CD40L

26
Q

Describe DC-SIGN

A

DC-specific intracellular adhesion molecule (ICAM)-3 grabbing non-integrin
DC specific ligand for ICAM-3 expressed on naive T cells
Promotes transient clustering between a DC and a T cell, allowing a DC to screen numerous T cells for a matching TCR

27
Q

Describe Dectin-1

A

DC specific type II C-type lectin
It binds to T cells to promote proliferation

28
Q

Describe CD80 and CD86 interactions

A

Co-stim molecules expressed on mature DCs
Regulate T cell activity

29
Q

Describe CD40-CD40L interactions

A

T cells can activate DCs via CD40L

30
Q

How do DCs direct B cell activation?

A

DC secretes cytokines to stimulate proliferation of B cells and Ig production
CD40-CD40L interaction at DC

31
Q

Where does DC interaction with NK cells occur?

A

Site of infection

32
Q

How are NK cells activate by DCs?

A

Pathogen activated DCs can activate NK cells through cell-cell contact and soluble signals
e.g. IFM-alpha, IFN-beta, IL-2, IL-12, IL-15, IL-18
Leads to NK cell secretion of IFM-gamma and cytolytic activity
Non-MHC dependent

33
Q

What can IFN-gamma and TNF release from NK cells do?

A

Cause maturation of DCs

34
Q

What peptides are presented by DCs?

A

Endogenous and exogenous
Can present antigen in context of either MHC I or II

35
Q

Where is endogenous material presented?

A

MHC I

36
Q

Where is exogenous material presented?

A

MHC I and II

37
Q

What is cross-presentation?

A

Loading of both endogenous and exogenous antigens on MHC I

38
Q

How does exogenous material become loaded onto class I?

A

Mechanism not yet fully understood
Hypothesis is that route of antigen internalisation is critical for loading onto MHC I
Receptor mediated endocytosis and phagocytosis results in presentation on MHC I
Dependence on TAP, suggesting cytosolic to ER transport involved

39
Q

What are the problems with cross-presentation?

A

Cross-presenting DCs are valid targets for cytotoxic T cells as they express viral peptides and MHC-I on cell surface

40
Q

What protects DC from lysis?

A

SPI-6

41
Q

What induces SPI-6 in DC?

A

Th1 cells

42
Q

What is an alternative way of cross-presenting?

A

Cross-dressing
Transfer of MHC-I molecules from tumour cell to DC

43
Q

What do DCs differ in?

A

The signals they respond to
The regulatory signals they transmit
They precursor cells they derive from
Their location
Stage of maturation

44
Q

What groups did early studies divide DCs into?

A

DC1 and DC2 based on their ability to induce either Th1 or Th2 responses

Infection and Immunity (33 decks)

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