LECTURE 5 Flashcards
What are naive T cells?
CD4+ and CD8+
What do naive T cell do after they exit the thymus?
Circulate in the blood passing in secondary lymphoid tissue
What happens if the naive T cells encounter an antigen in the secondary lymphoid areas?
They will proliferate
What do CD8+ cells do?
Kill infected cells
What do CD4+ cells do?
Secrete cytokines
What are naive T cells?
They are effector and memory precursor subsets
What cells do T cells recognise antigens on?
Antigen presenting cells (APC)
Where are APC found?
In the spleen and lymph nodes
What happens if APC are activated in the tissue?
They will need to find the infection so where else
What do T cells use to get around?
They use the blood and the lymphatics to get around the body
How do T cells enter the lymph node?
From the blood via high endothelial venules (HEV)
What is the T cell areas?
Is where the T cell is looking for antigens in the secondary lymphoid structures (rich in dendritic cells and macrophages)
What happens if a T cells is not activated?
They leave via the cortical sinuses and the process starts the next day till they find an antigen
What happens if a T cell becomes proliferated?
It is actively blocked
What do activated T cell differentiate to?
Effector cells and exit the lymph node
What does CAM =?
Cell adhesion molecules
What do chemokines and chemokines receptors do?
Synthesised cells and secrete cells while acting as a signpost
What happens with T cells in relation to chemokines?
T cells follow chemokines to look where they need to go
What are CAMs involved in?
Involved in holding the cells on the antigen presenting cells
What do CAMs mediate?
Cell-cell interactions
What are some examples of cell-cell interactions with CAMS
Naive T cell with HEV, T cell with APC, effector T cell with target cell
How do T cells contact APC?
Using CAMs
What do TCR do?
They scan APC peptides and MHC complexes
What happens if there is no recognition in APC/MHC complexes?
Disengages
What happens if there is recognition when the TCR scans APC peptide and MHC complexes?
There is a signal from the TCR complex
What are the steps that happen after the signal from TCR complex?
- Increased affinity of CAM interactions
- T cell divides
- T cell differentiate to effector cells and exist the lymph nodes
What is the LFA-1?
Leukocyte function associated antigen
What is ICAM-1?
Intercellular adhesion molecule
What do LFA-1 and ICAM-1 do?
Allow to cell to stick together while the decisions are being made
What affinity do T cells need?
Medium affinity
What does CD4 interact with?
Class II
What do CD8 interact with?
Class I
What happens once the T cell recognises the peptide on an MHC?
It drives a signal to alter and LFA1 binds to ICAM-1 making a better and more secure binding
Where does the first signal come from?
CD3 complex
How many signals does the T cell need to become fully activated?
3
What is signal 2?
CD28 complex
What is signal 3?
Cytokines
Why does T cells need signal 3?
To become an effector
How does the signal cause an effect?
The effector cells recognise the T cells and this is what starts the signal
What happens once T cells are activated by 3 signals?
They will proliferate and express ICO3 and CTLA-4
What does ICOS do?
Binds ICOSL on APC to induce cytokine secretion by T cells
What does CTLA-4 do?
Highly related to CD28 and shows a stronger binding than CD28
What does the binding of CTLA-4 do?
Delivers a negative signal to the activated T cell
What is CTLA-4?
It is an antagonist and limits the T cell response
What does CTLA-4 bind?
B7 and displaces the positive signal from CD28
What happens if you have a mutation in CTLA-4?
You have an over responsive immune response
What are they treating cancer patients with to enhance the immune response?
Anti-CTLA-4
Where is co-stimulation found?
On antigen presenting cells - CD28 and B71
What happens when there is activation of APC by pathogens?
It induces co-stimulation expression
What does the innate immune response do?
Upregulates b71/2 to allow for signal 2
What is the danger signal?
Ability to upregulates co-stimulatory molecules as a consequence of patten recognition receptor engagement
How many different signal 3s can happen depending on the effector?
3
TFG-beta signal 3 =?
Treg cells
IL-6 signal 3?
TFH cells
TFG-beta and IL-6 signal 3=?
TH17 cells
IL-12 and IFN-gamma signal 3?
Th1 cells
Il-4 signal 3?
TH2 cells
What are dendritic cells useful for?
Activation of naive T cells
What do macrophages and B cells do for T cells?
Present antigen in order to receive help from effector T cells
What are myeloid conventional DC cells also known as?
Dendritic cells
What are plasmacytoid DC cells helpful for?
Viral infection and secrete type 1 alpha and beta interferons
What do myeloid conventional cells do?
They sense danger as they have pattern recognition receptors
What happens once myeloid conventional cells sense danger?
They upregulates B7
Where are myeloid conventional cells located?
They are located in the peripheral sites and migrate to the lymph node which is where T cells are
What are examples of myeloid conventional cells?
DC(2.3)
What is the level of co-stimulatory molecules for DC(2,3)?
Very high
What do DC(2,3) express?
Adhesion molecules
What is cross presentation?
Some specialised proteins will take up proteins from the outside rather than presenting on class II they do on class I
What do macrophages express?
They express class II and B7
What happens when macrophages are activated by T cells?
They secrete inflammatory cytokines
Are macrophages good at phagocytosis?
Yes
Are b cells good at phagocytosis?
No
What does antigen binding to BCR do?
Upregulates B7 (provides signal 2 to activate T cells)
What is IL-2?
It is a potent autocrine T cell growth factor
What happens when IL-2 binds to IL-2R on an activated T cell?
Lots of T cell proliferation
What does IL-2 allow?
Rapid division of T cells, expands population of Ag-specific
What is IL-2 a target of?
Immunosuppressive drugs e.g. cyclosporine
What do effector T cells do?
Change expression of adhesion molecules
How is CD8 activated?
High levels of co-stimulatory activity and directly by infected APCs
