Lecture 6 - APC's / T cell Activation Flashcards
(35 cards)
Does initiation of adaptive immune response occur at the site of infection?
No! Ag’s are taken to secondary lymphoid organs and presented there by MHC’s, to activate adaptive immune response.
naive T cells enter lymphoid organs by crossing walls of ______, a process mediated by adhesion molecules.
High epithelial venules (HEV)
What cells express the co-stimulatory B7 molecule?
APC’s are the only cells that express B7
Name the 4 class of cell-suface adhesion molecules.
1) Selectins
2) Addressins
3) Integrins
4) Immunoglobulin superfamily members
What are Selectins, and give two examples.
Lectins that bind to carbohydrates.
Ex: L-selection, P-selectin
What are Addressins, and gives three examples.
Mucin-like vascular addressins have carbohydrate component in order to be recognized by Selectins.
Ex: CD34, GlyCAM-1, MAdCAM-1
What are Integrins, and give an example.
Integrins bind to various adhesion molecules.
Ex: LFA-1 (binds to Ig superfamily member ICAM-1)
What are Ig Superfamily Members, and gives three examples.
Targets for integrin binding.
Ex: ICAM’s, CD2, LFA-3
L-selectin is expressed by ____, and binds to carb parts of addressins, which are expressed on surface of ______.
- L-selectins are expressed by naive T-cells
- addressins (CD34 and GlyCAM-1) are expressed by HEV’s
- selectin-addressin interaction allows rolling of T-cell
After L-selectin:GlyCAM-1 and CD34 interactions allow ‘rolling’ of T cell, LFA-1 is activated by ______, causing what to occur?
LFA-1 is activated by chemokines, thus activating LFA-1 and inducing a conformational change of LFA-1.
Conformational change of LFA-1 results in higher affinity of LFA-1 for what molecule?
LFA-1 increases its affinity for ICAMS, thus prolonging cell-to-cell contact, and enabling diapedesis (mov’t of T cell between HEV, into lymph node)
After ‘rolling’ (diapedesis) for a while, if naive T cell does not find cognate peptide, what is its fate?
Naive T cell will eventually reach medulla of lymph node and enter efferent lymph vessel, return to bloodstream, and circulate back to other secondary lymph tissues.
What types of pathogens are presented by each:
Dendritic cells
Macrophages
B cell
- Dendritic cells: viral peptide Ag’s, allergens
- Macrophages: bacteria and yeast; (better at extracellular)
- B cells: soluble Ag’s; good at both intra and extracellular
Two signals are required for T cell activation. What are they?
1) binding of TCR to cognate peptide via MHC
2) co-stimulation signal of binding B7 (on APC) –> CD28 (on T cell)
Immature dendritic cells are called ____.
Mature dendritic cells are called _____.
Immature: Langerhans’ cells
Mature: interdigitating recticular cells
How is the role of immature dendritic cell different from that of mature dendritic cell?
- Immature dendritic cells DO NOT present Ag. Main role is to take up Ag (macropinocytosis)
- They then travel to Tcell zones of secondary lymphoid tissues, where they mature.
- Mature dendritic cells DO NOT take up new Ag, but present Ag to Tcells. Once mature, they express B7.1 and B7.2, and produce chemokine to attract naive Tcells.
Dendritic cells in epithelial tissue express B7 co-stimulator molecules. T/F
False! Dendritic cells only express B7 one they have matured, in the lymphoid tissue.
After a naive T cell has received the two signals of activation, proliferation occurs, which is driven by autocrine growth factor _______.
Interleukin 2
IL-2 receptors are present on naive T cells. T/F
True, however naive T cells express the low-affinity IL-2 receptor. Activated T cells express high-affinity IL-2 receptor AND secrete IL-2. When IL-2 binds to the hihg-affinity receptor, a signal is sent to that same T cell, inducing T cell proliferation.
Describe the structures of the low-affinity and high-affinity IL-2 receptors.
Low-affinity: only beta and gamma chains.
High-affinity: has beta, gamma, and alpha chains.
*All of these chains are TRANS-membrane.
What happens to a T cell that does not receive the secondary signal of B7:CD28 binding?
The T cell becomes anergic and dies (this is called Peripheral T cell Tolerance
How does the body ensure that T cell activation only occurs during infection?
Dendritics cells and macrophages must see foreign Ag before they can express B7, and B7 is required to activate T cells.
What happens to a T cell that receives ONLY the B7:CD28 secondary signal, but not the first signal of cognate Ag, presented by an MHC on APC?
This scenario has no effect on the T cell (this happens all the time).
How is B7 expression by macrophages induced?
Phagocytosis and breakdown of bacteria by a macrophage induces the expression of both MHC II and B7.
