M: Adaptive immunity 3 - Week 5/6 Flashcards
(39 cards)
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
What does “co-stimulation” require?
interaction between the molecule expressed on the T cells (known as CD28, CD80, CD86) on those activated APCs
Name 2 examples of co-stimulatory molecules that licensed DCs display
- CD80
- CD86
What does the induction of CD80 and CD86 on the DC enable activation of?
antigen specific CD4 T cells
On receiving signal 1 and 2, describe what happens to the CD4 T cell? (3)
- it now expresses CD40L
- and expresses IL-2R, secretes IL-2 and now proliferates
- differentiates [signal 3] to perform its effector function
What do activated CD4 T cells differentiate into based on the following conditions:
A) Early in infection
B) As infection persists
C) Worm/Helminth infection
A: Early in infection there is lots of IL-6 and TGFbeta cytokines produced by APC that drive differentiation into TH17. IL-6 also drives differentiation into TFH
B: IL-12, IL-18, and IFN-y produced by APC drives differentiation into TH1
C: IL-4 and IL-33 produced by APC drives differentiation into TH2
When there is a lot of TGF-beta produced by APCs (i.e. in steady state, normal conditions), what are CD4 T cells driven to differentiate into?
Regulatory T cells (Treg)
Describe TH17. What do they produce? (2) What does this achieve? (1)
characterised by production of IL-6 and IL-17, which helps with the recruitment of neutrophils to the site of infection
Describe TFH. what does TFH stand for and what do TFH cells do?
Follicular Helper Cells. Help with B cell proliferation and differentiation and thus the antibody response
Describe TH1. what do they produce? (2) What do they achieve? (2) What are they involved in? (1)
characterised by production of IFN-y and TNF. TH1 cells are very efficient at fully activating macrophages and also help B cells produce particular types of antibodies (IgG)
They are involved in the inflammation response during tissue damage
