M: Adaptive immunity 3 - Week 5/6 Flashcards
In addition to the binding of the peptide antigen-MHC complex by the TCR, are there any other signals required for full effector activation? What are these signals called?
Yes. They are called “Co-stimulatory signals”
What are the 3 signals required for full activation of the naive T cells?
Signal 1: TCR recognises antigen on MHC molecule
Signal 2: “Co-stimulation” for T cell expansion
Signal 3: Induction of T cell differentiation
In order to effectively activate naive CD4 and CD8 T-cells, what must an APC do? (2)
- Acquire and process antigen in compartments which gain access to MHC Class I and II pathways AND
- Interact with naive T cells to induce effector T cells
How do APCs interact with naive T cells to induce effector T cells? (5)
- they locate appropriate T cells (in the secondary lymphoid tissue)
- then they adhere to the T cells
- Present MHC associated peptides to T cells [signal 1]
- Provide “co-stimulation” [signal 2] for T cell expansion
- Induce T cell differentiation [signal 3]
What cells are the best antigen presenting cells (APCs)?
Are these cells a good stimulator of naive T cells?
Dendritic cells. They are the best equipped to activate naive T cells
No they are not.
What is the final outcome of the dendritic cell maturation pathway?
The activation of both CD4 and CD8 T cells
In regards to Dendritic Cells:
A) How efficient are they at capturing antigen?
B) What do they do in normal, non-inflamed tissue?
C) How much MHC II do DCs express in non-inflamed tissue?
D) What do DCs secrete? What does this achieve?
A: Very. However are poor stimulators of naive T cells
B: They constantly sample their surrounding environment for antigen (through multiple mechanisms)
C: Low level of MHC II on plasma membrane
D: TGF-beta - helps to suppress induction of strong immune responses
Why is migration of dendritic cells to the draining lymph nodes restricted in normal non-inflamed tissues?
T cells become activated in the lymph nodes. During infection, the DCs will migrate to the draining lymph nodes to activate the T cells.
In non-inflamed tissue, we don’t want to activate T cells when there is no need, so migration to these draining lymph nodes is restricted.
Where can Pattern Recognition Receptors (PRRs) be displayed? (3)
Locations include:
- surface of our cells
- cystolic compartments
- endosomic compartments
*depends on the PRR, some are displayed on surface of cells, some in cytosolic etc.
True/False: All TLRs form hetero-dimeric molecules
False. Only some. For example TLR 2 and 6 form a hetero dimer with each other, as well as TLR 1 and 2 forming a hetero dimer with each other
What initiates DC maturation?
DC binding to pathogens
What type of signalling induces DC maturation?
PRR signalling
- PAMPs on pathogens ligate the PRR on the DCs and stimulates their maturation
List the series of maturation events that the DC undergoes once bound (7)
- Migration of DC to draining lymphoid tissue
- Increased antigen processing
- Increased surface expression of MHC I and II
- Increased surface expression of adhesion molecules
- Increased expression of co-stimulatory molecules (CD80, CD86)
- Increased secretion of cytokines
- Maturing DCs lose their capacity to capture antigen but are now able to activate T cells
How do DCs migrate to the draining lymphoid? (2)
- via the lymphatics (conjunctiva) or
- spleen via blood (if intraocular)
Why are the adhesion molecules important for binding of APC to T cell?
they allow the LFA1 on the T cell to bind to the adhesion molecule on the DC - resulting in these 2 cells staying tightly connected for quite some time