T Cell Activation and Generation of Effector T Cells Flashcards
MHC class 1 presents {?} antigen but MHC class 2 presents {?} antigen
MHC class 1 presents endogenous antigen but MHC class 2 presents exogenous antigen
Upon leaving the Thymus what do Naiive T celle enter lymph nodes via?
Naiive T cells upon leaving the thymus enter lymph nodes via a high endothelial venule which is a specialised blood vessel
T cells use {?} lymphatic vessels to move between lymph nodes
T cells use efferent lymphatic vessels to move between lymph nodes
Dendritic cells presenting an antigen can move from a site of infection through an {?} to the lymph node to present to naiive T cells
Dendritic cells presenting an antigen can move from a site of infection through an afferent lymphatic vessel to the lymph node to present to naiive T cells
Activated T cells move into the circulation through the {?}. And move to sites of infection due to {?} instead of circulating.
Activated T cells move into the circulation through the thoracic duct (vena cava). And move to sites of infection due to chemokines instead of circulating.
Explain why a T cell would recirculate and what this means?
If a naiive T cell does not encounter its specific antigen (being presented by a dendritic cell) in either of the lymph nodes it travels through (only 2 LNs?). Then it will recirculate and go back into the first lymph node again.
Naiive T cells are activated in {?} lymphoid organs such as {?}
Naiive T cells are activated in secondary lymphoid organs such as lymph nodes and spleen
How do naiive T cells encounter their antigen in a LN when the antigen would likely be at the site of infection (where the pathogen is)?
As dendritic cells presenting the antigen move into LNs by afferent lymphatic vessels
Explain how there are 2 stages of activation from a naiive T cell
- There is activation of the naiive T cell to an effector cell
- And there is activation of the effector T cell (can happen in periphery at sites of infection) which is functional differentiation of the cell
Name 3 cells that can activate naiive T cells
- Dendritic cells
- Macrophages
- B lymphocytes (can pick up soluble antigen with their BCR on surface and present to T cells)
Only activated professional APCs such as the ones above present high levels of MHC class 2
Professional APCs express {?} and high levels of {?} when activated
Professional APCs express co-stimulatory molecules and high levels of MHC2 when activated
Name the 3 signals needed for a T cell to be fully activated and differentiated into an effector or memory T cell
- Signal 1: Antigen recognition
- Signal 2: Co-stimulation
- Signal 3: Cytokines - Part 3
Which of the 3 professional APCs is the costimulatory signal mostly found on
Dendritic cells
- but also found on macrophages and B cells
The co-stimulatory signal for a T cell involves the binding of {?} from a T cell to {?} on the APCs
The co-stimulatory signal for a T cell involves the binding of CD28 from a T cell to B7 on the APCs
- B7 is a common term for B7-1 (CD80) and B7-2 (CD86)
Dendritic cells that have been activated in the presence of PAMPs upregulate {?} and {?}
Dendritic cells that have been activated in the presence of PAMPs upregulate B7-1 (CD80) and B7-2 (CD86)
Name 2 important cyctokines in the activation of T naiive T cells by an APC
IL12 released by the APC
IL-2 released by the T cell (paracrine)
- also IL-6 IL-4 and TGf-beta
T cells recognise antigen with or without costimulators, causing the expression of {?} on T cells
T cells recognise antigen with or without costimulators, causing the expression of CD40L on T cells
Explain what CTLA-4 is and what it binds to
This is a signal on the T cell that can overide the signal of CD28 and can stop the T cell from being activated - also binds to B7-1 (CD80) and B7-2 (CD86) and so in a way it competes with CD28
Name a negative T-cell co-stimulator that has been exploited for cancer immunotherapy
PD-1 (programmed death protein 1)
CTLA-4 is expressed aproximately {?} days post stimulation of the T cell
CTLA-4 is expressed aproximately 2-3 days post stimulation of the T cell
CTLA-4 has {?} affinity than CD28 for B7-1 (CD80)
CTLA-4 has higher affinity than CD28 for B7-1 (CD80)
- Even though the peak levels of expression are lower than CD28, affinity is higher
Describe HOW detection of PAMPs can help to induce T cell activation (this is the mechanism of the danger hypothesis)
- this is also how a cd4+ cell choses between TH1 and TH2
- Dendritic cells with their MHC bound to a TCR and CD80/86 bound to CD28 (and also other co-signals such as CD40L) may detect some PAMPS by their PRRs.
- These PRRs will cause signalling which can allow for cytokine release to affect the T cell and drive it to activate.
- These cytokines can push the cell become either TH1 or TH2.
- So PRR binding stimulates:
- B7 (CD80/CD86) increase
- Polarising cytokine release
So what is an important function of this 3rd signal of cytokines on T cells?
Induction of T cell polarisation - so cytokine environment (from the APC) causes the cell to decide what it will differentiate into, do not know if this is for CD8+ cells also but CD4+ is below
When cytokines bind to T cells, what happens to induce their polarisation?
- is signal 3
In response to certain cytokines, each effector T cell will express a master controller transcription factor which controls the expression of the cytokines expressed by that T cell
IL-2 is an important {?} chemokine for T cells. (describe the mechanism of action in one word)
IL-2 is an important autocrine chemokine for T cells
Without IL-2 T cells can’t {?}.
Without IL-2 T cells can’t proliferate.
Name a way that IL-2 function on T cells is regulated (decreased)
- Treg cells have more IL-2 receptors than the naiive T cell so the IL-2 binds to the T reg instead
Describe the functions of the below surface receptors - these are expressed one after the other over time
- CD69 (on tissue resident cells) allows for retention in the lymph node so they can be fully activated
- CD25 is receptor for IL-2
- CD40L is needed for further activation by denderitic cells
- CTLA-4 is expressed days after to calm/regulate the response
Upon activation, what does a T cell do and what choice does it need to make
- Proliferation by IL-2
- Differentiation
- Choice to become effector or memory cell
What are effector cytokines?
These are the cytokines that are produced by fully differentiated T cells such as IL-10 to reduce inflammation by a Treg cell
What are polarising cytokines?
- Are cytokines that polarise a T cell instead of having a distinct effect.
- So they cause the naiive T cell to differentiate. (are signal 3).
- Are generated by the APC.
What is the brief function of:
- TH1 cells
- TH2 cells
- TH7 cells
- Treg cells
- TH1 cells: activate macrophages to enhance their ability to destroy intracellular pathogens
- TH2 cells: recruit cells for anti-parasitic responses
- TH7 cells: recrutment of neutrophils particularly in an antibacterial response
- Treg cells: decrease/regulate immune response
- TFH cells: signal to B cells to differentiate and produce antibodies
TH1 polarisation occurs in response to the presentation of {?} by an APC
TH1 polarisation occurs in response to the presentation of intracellular pathogens such as viruses and bacteria by an APC
- Remember that TH1 cells are for removing intracellular pathogens
Important transcription factors that regulate TH1 polarisation are {?} and {?}
Important transcription factors that regulate TH1 polarisation are STATs (STAT1 and STAT4) and T-bet
TH1, via the release of {?}, causes enhanced action of macrophages and stimulates B cells to release antibodies that opsonise bacteria and activate complement.
TH1, via the release of IFγ, causes enhanced action of macrophages and stimulates B cells to release antibodies that opsonise bacteria and activate complement.
TH2 cell polarisation occurs in response to {?} as well as other conditions such as {?}.
TH2 cell polarisation occurs in response to parasites as well as other conditions such as asthma and allergies
The main TH2 polarising cytokine is {?}. Which os produced by eosinophils, basophils and mast cells.
The main TH2 polarising cytokine is IL4. Which os produced by eosinophils, basophils and mast cells.
The main polarising cytokine in TH2 cells (IL4) causes activation of the transcription factors {?} and {?}. {?} promotes activation of IL4 and IL13 genes.
The main polarising cytokine in TH2 cells (IL4) causes activation of the transcription factors STAT6 and GATA3. GATA3 promotes activation of IL4 and IL13 genes.
- So the IL4 is an autocrine response
Describe the functions of TH2 cells fully
- Which cytokines do they secrete?
- Which class switching do they initiate?
