T Cells Flashcards
What is a T cell? How does it develop? Where does it reside?
lymphocyte of common lymphoid progenitor in the bone marrow. Migrates to thymus to develop.
All T cells have multiple identical TCRs on cell membranes.
After development, they migrate to secondary lymphoid tissue and reside in T cell zones, such as the spleen, GALT, lymph nodes, etc.
How are T cells different than B cells? What roles do T cells play in the immune system IN GENERAL? How do T cells and B cells differ in terms of immunoglobulins?
T cells recognize peptide antigens only.
B cells can recognize peptides, nucleic acids, lipids, carbohydrates, soluble antigens, particulate.
T cells are MHC restricted.
T cells kill cells infected with intracellular pathogens and also modulates activities of other immune cells to surmount an attack on extracellular pathogens by excreting cytokines and chemokines.
T cell Ig are never secreted and only recognize MHC
B cell Ig can be on the cell membranes or secreted.
Describe the structure of a TCR. How is this similar or different than an Ig?
alpha&beta heterodimers or delta&gamma heterodimers. Alpha/beta is more popular.
each heterodimer has a constant domain and a variable domain. Looks like the Fab fragment of an Ig. Both heterodimers are anchored via constant domains to the cell membrane.
What are Gamma/Delta T Cells? How are they different than Alpha/Beta? Where are they found? CD4 or CD8?
Gamma/Delta T cells are not part of the acquired immune response. They do not mature in the thymus. They mature extathymically. They are not MHC restricted and do not recognize peptides. They recognize lipids instead.
Found primarily in intestinal epithelial tissue.
They are CD4 and CD8 negative.
What is CD3? Where is it expressed? What is its structure?
Expressed on all T cells.
Protein complex that initiates signaling to the nucleus when T cell binds cognate determinant.
2 epsilon domains, 1 gamma, 1 delta domain and 2 zeta cytoplasmic domains.
When TCR meets its cognate antigen on MHC and receives appropriate signaling, what set of proteins signals to the nucleus? How does this work?
CD3 signal transduction unit senses conformational change and via all 6 protein subunits of CD3 signal to the nucleus using ITAMs = immunoreceptor tyrosine-based activation motifs
What are ITAMs?
immunoreceptor tyrosine-based activation motifs
Name does not really matter.
Know that this is the signaling piece of CD3 when TCR meets its cognate antigen. Signals to the nucleus.
What are CD4 and CD8? What are their purposes?
TCR co-receptors. Only CD4 or CD8 is found on each T cell, not both.
CD4 T cells assist binding to MHC Class II
CD8 T cells assist binding to MHC Class I
Help bring T cells in close proximity to respective MHC presenting cells in order to sample the cognate determinant.
What is CD28
Surface marker on all T cells that bind to B7 on antigen presenting cells. This binding is critical for activation of T cells
What is Fas ligand or FasL?
FasL is not exposed on all T cell surfaces, otherwise that would cause apoptosis of any cell it touches. Effector CD8 T cells have FasL in vesicles so when they release granzymes into the proximity of the cognate positive cell, FasL is exposed on the cell surface.
FasL binds to 3 Fas proteins on the infected cells surface and induces apoptotic death via FADD (fas associated death domain) and the caspase cascade – FADD cleaves procaspace 8 to caspase 8 and procaspase 10 to caspase 10. This leads to cell death (see patho notes)
What are tingible body macrophages?
Macrophages found in the thymic cortex that phagocytose apoptotic T cells.
Have tingible appearance on staining due to accumulation of chromatin degradation.
The cortex of the thymus has what cells in it?
immature thymocytes, tingible body macrophages, cortical epithelial cells
The medulla of the thymus has what cells in it?
Hassell’s corpuscles, macrophages, maturing thymocytes and dendritic cells
Describe the general route of thymocytes as they mature in the thymus.
Immature thymocytes enter the thymus from the blood stream through high endothelial venules (HEV).
First, they proliferate while entering the cortex where they begin expressing the beta chain of the TCR or the gamma/delta chains–whichever comes first. (the first one is the what the cell will become)
They express the TCR, CD3, CD4 and CD8 - yes, both.
Next, in the cortex, they undergo positive selection. The cortical epithelial cells present both MHC class I and II with self-peptides. The thymocytes receive a positive signal to survive and mature when they bind to MHC & peptide. Otherwise, no signal = apoptosis.
Then, beginning in the corticomedullary junction into the medulla, the thymocytes undergo negative selection. By this point, they are either CD4 or CD8 positive. In negative selection, if the TCR binds to tightly to self-reactive antigens on MHC:peptide complex, they will receive signals for cell death.
Otherwise, they move out of the thymus as naive T-cells into secondary lymphoid tissues.
How do thymocytes determine whether to become an alpha/beta or gamma/delta T cell?
If beta chain rearrangement occurs first, then the cell will be an alpha/beta T cell.
If gamma and delta rearrangement occurs first, then the cell will be gamma/delta.
In the thymus, how do alpha/beta T Cells develop?
After proliferation, thymocytes rearrange beta chain genes and produce a beta chain on the cell surface with CD3 complex.
While waiting on the alpha chain to rearrange and produce, pTalpha binds to the beta chain as a surrogate. pTalpha is an invariant chain that stabilizes the beta chain. The beta chain would degrade if it does not have pTalpha or alpha chain to bind.
What is pTalpha?
surrogate invariant chain for alpha chain of alpha/beta t cell until alpha chain is made.
What happens if there is a genetic deficiency of pTalpha?
SCID
beta chains will not be stabilized by pTalpha (while waiting on alpha chains to rearrange and produce), so beta chains will degrade –> very low production of alpha/beta T cells.
