Flashcards in Immuno 9 Deck (69)
What is an effector T cell?
a daughter cell of an activated T cell that has fully differentiated and is ready to perform its effector function.
How are effector T cells different from naïve T cells?
(1) They do not require co-stimulation to be activated to perform their effector function. The only signal they need is recognition of their cognate peptide presented by an MHC molecule.
(2) They express an array of surface adhesion molecules that direct them to appropriate tissues and inflammatory sites.
L-selectin (or CD62L) is expressed on the surface of what kinds of T cells?
naïve CD4+ and CD8+ T cells. and CD4 effector cells
What does L-selectin (CD62L) do?
It binds to adhesion molecules (Glycam-1 and CD34) that are found on the surface of endothelial cells that line the high epithelial venules on secondary lymphoid tissues. Only cells that express L-selectin can enter these tissues.
Why is L-selectin not found on effector CD8 T cells?
because effector CD8 T cells have no positive role in a secondary lymphoid tissues, while they would have a destructive function. They would kill any APC that presents their cognate peptide on MHC molecules.
Why do CD4 effector cells do need to have L-selectin on their surface?
so that they can cycle through the various secondary lymphoid tissues to serve as the secondary activators of antigen-specific B cells.
Which T cells express VLA-4 on their surface?
upregulated on effector T cells
What does VLA-4 do?
This integrin receptor binds to an integrin ligand called VCAM-1 that is expressed on activated endothelial cells. When VLA-4 binds to VCAM-1, it facilitates the movement of the effector cell across the vascular endothelium into an inflammatory site.
What kinds of T cells is LFA-1 present on the surface of?
All T cells
What kinds of T cells is CD-2 present on the surface of?
All T cells (and NK cells)
What kinds of T cells is CD-4 present on the surface of?
All T cells
What kinds of T cells is TCR present on the surface of?
All T cells
What kinds of T cells is CD-44 present on the surface of?
All T cells
What kinds of T cells is CD45RA present on the surface of?
found on naïve T cells
What kinds of T cells is CD45RO present on the surface of?
found on activated and memory T cells
What are the three main types of effector T cells?
(1) CD8 effector cells that are known as either cytotoxic T cells or CTLs, or even killer T cells.
(2) T helper-1 type effector CD4+ T cell
(3) T helper-2 type effector CD4+ T cells
There are a couple of other types of effector T cells, but these are the three that are most important for this course.
What is the primary function of CD8 effector cells, known as CTLs?
to kill infected cells, resulting in premature termination of the replicative cycle of the pathogen. Think intracellular and viruses
CTLs produce several effector molecules (cytotoxins) that are responsible for their host cell killing function. Name them.
These are Fas ligand, perforin, granzymes, and granulysin.
CTLs also produce some important cytokines that are involved in development of immune responses. Name these.
LT and IFN-gamma
What is the primary function of CD4 effector cells?
The primary role of effector CD4 T cells is to supply the critical secondary activation stimuli that are needed to activate an antigen-specific B cell and to drive their differentiation. Both TH1 and TH2 cells have this function.
TH1 cells also function to 'classically' activate macrophages, making them more phagocytic and more bacteriocidal.
What are the important effector molecules of CD4 effector cells?
CD40-ligand and the cytokines that they produce.
What cytokines do TH1 cells produce?
IFN-gamma, GM-CSF, TNF-alpha, LT, and IL-3
What cytokines do TH2 cells produce?
IL-4, IL-5, IL-10, IL-13, and TGF-beta
There are two additional CD4+ effector T cell types that you should know about, namely:
(1) Regulatory T cells (or Tregs): these cells’ function is to prevent activation of self-reactive T cells.
(2) TH17 Cells: these cells induce production of neutrophil chematractants and antimicrobial peptides by several cell types.
A naïve T cell (CD4+ or CD8+) requires what two signals of activation?
(1) recognition of cognate antigenic determinant via the TCR, and
(2) costimulation, in the form of B7 molecules on the APC binding to CD28 on the T cell.
What happens if a naive T cell receives both of these signals?
When these signals are received, the T cell begins to proliferate (driven by the autocrine growth factor, IL-2).
Once the resulting daughter T cells have fully differentiated in effector cells, they move into inflamed tissues and sample peptide:MHC complexes. If they recognize their cognate peptide bound to an MHC molecule, they will perform their effector function.
In the case of an effector CD8 T cell, that effector function is to limit the pathogen's replicative cycle by killing the infected cell by initiating programmed cell death (or apoptosis). By killing the infected cell, they halt the replicative cycle of the pathogen and cause release of the pathogens that have accumulated inside the cell, making them susceptible to other immune responses (e.g. complement, antibodies/phagocytes, etc.)..
What is Perforin?
A primary effector molecules made by effector CD8+ T cells that is a membrane active molecule that inserts into host cell membranes as a multimeric complex (similar to membrane attack complex), forming pores in the cytoplasmic membrane of the cell.
What is Granulysin?
A primary effector molecules made by effector CD8+ T cells that is another membrane active molecule that can form pores in the cytoplasmic membrane of host cells. It also appears to have antimicrobial properties.
What are Granzymes?
Primary effector molecules made by effector CD8+ T cells that are serine proteases that initiate the apoptotic pathway (programmed cell death) if they gain access to the host cell cytoplasm.
When a CTL degranulates, it releases these three molecules. Perforin and granulysin create pores in the cytoplasmic membrane of the host cell, allowing granzymes to gain access to the cytoplasm of the cell (with help).
Once perforin is in the cytoplasm, it initiates the caspase cascade that results in programmed cell death (apoptosis).