T cell effector functions Flashcards
Describe the homing of effector T cells to sites of infection
After completing differentiation in the lymph node, dendritic cell nursery
Clones of effector CD8 T cells and effector CD4 Th cells leave the secondary lymph tissue, enter circulation and seek out sites of infection/antigen
The naïve T cells upon differentiation into effector T cells, have changed their cell surface molecules that allow them to home into sites of infection
T cells encounter antigen in the peripheral tissues and there they also require antigen-specific conjugate pairing with the target cell (that have intracellular pathogens)
The effector T cells connect at the synapse and deliver their effector molecules to the target cell to mount a response
Describe the role of cytokines and cytotoxins for effector T cell function
Cytotoxins kill target cells, released only by effector CD8 cytotoxic T cells
Cytokines alter the behaviour of the target cell (all effector T cells make cytokines)
Cytokines perpetuate & enhance the immune response in that area by binding to cytokine receptors (cell-surface)
The intracellular signals generated by these interactions induce changes in gene expression within the target cell
Describe the function of cytotoxic CD8 effector T cells at sites of infection
Describe the function of effector CD4 helper T cell subsets (Th1, Th2, Th17, Tfh and Treg) at sites of infection/injury
Give 2 examples of differences in cell surface molecules between naïve and effector T cells
Naïve T cells express L selectin, not VLA-4
Naïve T cells express CD45RA, not CD45R0
All effector T cells leave secondary lymph tissues, enter circulation and seek out sites of infection
True or False
False, CD4 Tfh cells move to the B cell zone to activate a B cell response (don’t leave the lymph node)
Which cell surface receptors do naïve T cells have?
Unique TCR, CD4 or CD8, L-selectin, LFA-1, CD2, CD44, CD45RA
Which integrin is upregulated on effector T cells for homing to inflamed tissue?
VLA-4
What is the adhesion molecule that is activated on the endothelial cells of inflamed target cells and is primed for the recognition of VLA-4 on effector T cells?
VCAM-1
Which interaction allows the effector T cells to leave the blood stream and enter the inflamed tissue? How?
VLA-4 & VCAM-1 interaction halts the passing effector T cells and directs them to the infected tissue
Which cell surface molecules are expressed in both naïve and effector T cells, but are expressed far more in effector T cells than naïve T cells
CD2 and LFA1 (expressed 2-4 times more)
When TCR engages with antigen presented by the T cell, what happens to other cell surface molecules?
The TCR engagement with the antigen presented by the target cell, induces LFA-1 to go through a conformational change that allows it to have a more long-lived interaction with ICAM-1
Why is effector T cell activation less strict than naïve T cell activation?
Effector T cell activation requirement is less strict than the activation of naïve T cells as co-stimulation (CD28 and B7) is not needed for T cell recognition of antigen at the infection site
This means that T cells are now able to kill any type of cell that becomes infected with a virus
How do effector T cells exert their functions?
Conjugate pair with target cell
Localised area of contact between the two cells
T cell synapse formed, where the T cell receptor and the co-receptor bind the MHC molecule and peptide complex
At this synapse, the effector molecules made by the T cell are delivered to the target cell
These are the cytokines and the cytotoxins
5 min contact time required for the synapse to form and the enzymes to be dropped
What is the difference between cytokines and cytotoxins, in terms of their production style
Cytokines are made only after the effector T cell has made a conjugate pair with the target cell
Then upon demand, they are delivered to the target cell
They are never made and stored in the CD4 T cell for future use
However, the cytotoxins are manufactured and stored in lytic granules before and encounter with the target cell
The killing mechanism of CTLs are similar to which cell type?
NK cells
What are the cytotoxins that CD8 T cells release & brief descriptions of them:
Granzymes (family of serine proteases)
Perforin (membrane disrupting protein)
Serglycin (proteoglycan which interferes with glycan structures)
All of the above make pores in the target cell
Granulysin (is a detergent like protein that associates with membranes and dissolves them)
All are very potent, dropped right at the point of contact
CD8 T cells kill which cells
cells overwhelmed by intracellular infections
The infected cells are sacrificed
killing is targeted, upon recognition, the CTLs contact, polarise and release the lytic granules
Another mechanism by which the CTLs kill target cells:
CTLs express Fas-L
which binds the death inducing Fas-R on the target cells
This induces apoptosis, without granules
Plays a minor role in killing by CD8+ CTLs
How do CD8 T cells kill many, many cells
As target cell starts to die, CTL is released and starts to make new granules (regenerate their granules)
Once new granules have been made, CTL is able to kill another target cell