L5: T Cell Development and Diversity Flashcards
What is a T cell?
cell derived from the common lymphoid progenitor that has a TCR (T cell receptor). They kill cells infected with viruses and other intracellular pathogens. They supply helper signals which activate B cells and macrophages.
Where are T cells generated? Where do they mature and develop?
Bone marrow. Then move to thymus to develop. Then secondary lymph tissue
What type of Ig molecules do T cells secrete?
T cells do not secrete Immunoglobulin molecules.
What links the alpha and beta chains of the TCR on T cells?
disulfide bonds
What are the alpha and beta chains of the TCR composed of?
a constant and variable region
What are the two lineages of TCR on T cells? Which is more common?
alpha-beta and gamma-delta.
Most cells are alpha-beta
What are the differences between alpha-beta T cells and gamma-delta T cells?
gamma-delta T cells do not recognize peptide/MHC complexes (not MHC-restricted), found primarily in mucosal epithelium, they mature outside the thymus, and are thought to have a significant role in recognition of lipid antigens
What type of antigens do gamma-delta T cells recognize?
lipids and carbohydrates
What is the CD3 complex?
signal transduction unit for the TCR. It is found on all T cells.
What are ITAMS?
immunoreceptor tyrosine-based activation motifs. They reside on the intracellular part of the CD3 complex. They initiate signaling cascade upon antigen-recognition through the TCR.
What happens in T cells with defective CD3 complexes?
They are unable to become activated after recognizing an antigen
Describe the structure differences between CD4 and CD8.
CD4 is a single chain, set of 4 Ig-like domains.
CD8 is a heterodimer composed of an alpha and beta set of chains with Ig domains.
What is the CD28 protein?
It s a T cel surface marker that binds B7 molecules on antigen presenting cells (co-stimulation). It is found on all T cells.
What type of cells have B7 molecules?
only professional antigen presenting cells.
What is the Fas ligand molecule?
T cell surface marker that binds to Fas expressed on the surface of target cells, initiating apoptosis.
What are adhesion molecules?
Surface proteins on T cells that initiate interactions between T cells and APC or target cells as well as vascular epithelium
How is the thymus organized?
It is divided into two primary regions: the cortex and the medullary region.
Cortex has many T cells and network of epithelial cells. Has some macrophages also.
Medullary region is highly populated with dendritic cells and has Hassall’s corpuscles. Negative selection (removal of self T cells) occurs in medullary region.
There is a corticomedullary junction between the two areas.
What is Hassall’s corpuscle?
a site of cell destruction of dying thymocytes.
Where does positive selection of thymocytes occur in the thymus?
In the cortex.
What happens to T cells when they enter thymus?
They move into cortex and they begin to proliferate rapidly. The cortical epithelial cells in the thymus express both MHC class I and II molecules. T cell begins to rearrange TCR genes. Beta first, then alpha, then cell expresses complete T cell receptor on surface, expressing CD3 and alpha and beta as well as both CD4 and CD8. At this point T cell type is not determined. Positive selection occurs. If T cell can react enough with cortical epithelial cells, they will receive survival signals and change their surface phenotype and start moving to the medullary region. By the time it reaches the corticomedullary junction, it is either a CD4 or CD8 cell type. In the medullary region they undergo negative selection for self-derived peptides. If it has high affinity for any antigen-presenting cells in medullary region, it will be terminated by apoptosis. If not, it will leave the thymus and enter circulation for travel to secondary lymphoid tissue
What is a tingible body macrophage?
a macrophage in cortical region of thymus that takes up dying lymphocytes. They stain very darkly (tingible)
What type of CD+ are T cells in the cortex of the thymus?
They are double positive, meaning they express both CD4 and CD8 at the same time until they are positively selected for one or apoptosis.
What are the first TCR variable region genes to rearrange?
beta, gamma, and delta chain genes.
What would happen if gama and delta chain rearrangement were to occur first?
T cell will be a gamma-delta T cell
What would happen if beta chain rearragnement is the first to happen?
It will associate with an invariant chain (pT-alpha; a surrogate alpha chain) and the CD3 complex to form the pre-T cell receptor complex. Once the pre-TCR is epxressed, beta, gamma, and delta gene rearrangement cease.
pre-T cell begins to proliferate and alpha chain gene rearrangement begins and associates with beta chain.
Is alpha chain rearrangement analogous to heavy or light chain rearrangement in B cells?
Light chain - single constant domain, a V region joined to a J region segment.
Is beta chain rearrangement analogous to heavy or light chain recombination?
Heavy chain - single V, single D, single J region gene segment
What do RAG enzymes do?
catalyze recombination of single V region with a single J region or with a J and a D region segments.
What is first step in B rearangment?
Single D segment joins to single J segment to form a DJ junction. This then joins a single V region gene segment.
How can you determine the stage at which neoplastic events take place in T cells?
look at the surface phenotypes. If it has CD34 it is in the bone marrow, still in development. Etc.
If a T cell tumor has CD3 and CD8 on its surface, what stage did the neoplasty occur?
occurred in adult T-cell. Can be anywhere in the periphery.
If a neoplastic event takes place in a stem cell, what surface markers would you expect on the surface? where did this occur?
CD34, bone marrow
If a T cell tumor has CD10, CD19, and CD20 on its surface, what stage did the neoplasty occur?
in the lymphoid progenitor, in the thymus.
What cell surface markers are present in the thymocyte stage of T cell development? where are thymocytes found?
CD1, thymus
If cytokeratins are found on the surface of a T cell tumor, what developmental stage did this occur in and in what location?
occured in a thymic stromal cell or epithelial cell. Happened in the thymus.
