Flashcards in L17_T-Cell Immunity Deck (25)
What two signals does a naive T-cell need on a regular basis to stay alive?
Just a "tickle" from self MHC receptors (This wont be a strong binding because the TCR should not bind the self peptide strongly). Also all naive T-Cell express IL-7 receptor and this needs to be stimulated by IL 7 which is bound to the extra cellular matrix
Describe the accessory molecules that help control routes of T Cell migration.
Selectins, integrins, and chemokine receptors control th emigration of naive t-cells in and out of lymph nodes and of effector and memory t-cell to sites of infection
Describe how accessory molecules help strengthen the adhesion of T-cells to APCs and why this is so important.
Integrins help keep the T-cell in contact with an APC, the affinity of this reaction is increased by cytokines produced when the TCR recognizes its cognate antigen. This is important because a T-cell must stay in contact with an APC for 6-12 hours to be activated.
name two different receptors on t-cells for costimulators expressed on APCs
CD28 (for B7) and CD40L (For CD40)
Give an example of an integrin binding pair between a T-cell and an APC
What are the 2 signals that a T-cell must receive to be activated?
MHC peptide - makes sure reaction is antigen specific
Costimulatory B7- expressed by APCs only when a harmful microbe is present.
Describe the difference between B7-1 and B7-2
B7-2 is constitutively expressed at low levels on unstimulated DCs and blood monocytes and is responsible for the initial interaction with CD28 on T-cells. B7-1 comes up later and is what sustains the interaction with T-cells if the expressed peptide is from a pathogenic source and dangerous to the host.
Is CD28 mediated costimulation required for effector and memory T-cells?
No, only for initial interaction with naive t-cells
What are the 3 types of effector T-cells?
Cytotoxic T Cells, Th1 Helper T-cells, Th2 Helper T-cells
What is the basic job of a Killer T-cell (CD8+)
To induce apoptosis in infected cells
What is the job of a Th1 helper T-cell?
Activates macrophages, induces B-cells to produce opsonizing antibody
What is the job of a Th2 helper T-cell?
Activates B-cells to make neutralizing antibody and has various effects on macrophages.
What does IL-2 do?
It is a T-cell growth factor (it may also have effects on B-cells and macrophages)
When does a helper T-cell determine if it is Th1 or Th2?
After it recognizes its cognate antigen and replicates. Which destiny depends on the environment.
What signals are required for a T-cell to activate a macrophage or B-cell?
MHC peptide and The T cell must present CD40L to bind to the CD40 receptor on both b-cells and macrophages. Once this happens specific cytokines are used to stimulate the cell to do various things
List the cytokines that a Th1 helper T-cell releases and what the effects are
IFN-gamma and CD40L - activates macrophage to destroy engulfed bacteria
Fas Ligand of TNF beta - kills chronically infected cells releasing bacteria to be destroyed by fresh macrophages
IL2 - T-cell proliferation
IL3 and GM-CSF induced production of more macrophages in bone marrow
TNF alpha and beta activates endothelium to allow macrophages into infected site
CCL2- macrophage chemotaxis
How would CD8 primary cells need help from CD4 cells?
CD4 cells are much better producers of IL2 and the CD8 may need this to proliferate to an effective level
What cytotoxic effector molecules do CD8 Tcells express?
Perforin, granzymes, granulysin, Fas Ligand, IFN gamma, TNF alpha and Beta
What is the fast killing route that CD8 T-cells use?
granzymes and perforin (induce apoptosis, rearranges excretory pathway to target specific direction of cell
What are the slower routes that CD8 T-cells use?
Membrane TNF, fas ligand, IFN gamma
How does a CTL avoid being killed by its own mechanisms?
It has Cathepsin B which coats its vesicles and it has protease inhibitors that prevent granzyme B from inducing apoptosis
How is a T-cell response terminated?
CTLA 4 (which is not expressed in naive T-cells) begins to be expressed after activation. Eventually it outcompetes CD28 for B7 and sends down-regulating signals to the cell
What are some other factors besides CTLA 4 that play a role in shutting down the immune response?
Elimination of antigen
Elimination of other stimuli
IL-2/IL-2R signaling (via T regulatory Cells)
Killing by immunoregulatory cells
How does T-cell become anergic?
If it encounters it cognate andtigen MHC but does not receive costimulation.