Immunology 5 (Kyle) Flashcards
What is a T cell ?
A T cell is a lymphocyte that is produced in the bone marrow, migrates to and matures in the Thymus, and differentiates into cells that either kill target cells that bear their cognate peptide: MHC Class 1 complex or supply help to other immune cells via production of cytokines.
How do T cells recognize a specific antigen?
T cells recognize a specific antigen through their T cell receptors.
Where does a T cell come from ?
Common Lymphoid Precursor and bears a TCR
Do T cell s secrete immunoglobulin molecules?
No
Describe the structure of AB T Cells
Most T cells bear a T cell receptor (TCR) that is composed of an A and a B chain
What do T cells do ?
Kill cells infected with viral or other intracellular pathogens
Supply helper signals which activate B cells and macrophages.
What are the 4 regions of a T cell receptor?
Variable region which binds the Ab
Constant Region
Transmembrane Region
Cytoplasmic Tail
What is an important surface marker on T cells that was mentioned in lecture.
What does it do?
CD3 is the signal transduction unit for TCR
Initiate signaling cascade upon antigen-recognition through T cell receptors
What are the Co receptors for the T cell receptor?
CD4 and CD8.
What does CD4 do ?
Has high affinity for MHC Class 2 molecules
What does CD8 do ?
Has high affinity for MHC Class 1 molecules
What binds to B7 molecules on antigen presenting cells ?
CD 28
What does the FAS Ligand do ?
Can bind to Fas expressed on the surface of target cells initiating Fas-mediated apoptosis
What do adhesion molecules do ?
Adhesion molecules initiate interactions between T cells and APC or target cells
What are the two regions of the Thymus ?
The Cortex and Medulla
What happens in the subcapsular region of the thymus (Think T Cell maturation)
T cells proliferate and differentiate to double positive CD3+ Thymocytes
What are the first chains to undergo rearrangement in the TCR variable region ?
Beta, Gamma, and Delta
If gamma and delta chain rearrangement are successful before beta chain rearrangement, what will the T cell be ?
Gamma, Delta T-Cell
What are the two distinct populations of T cells?
Gamma Delta T Cells and Alpha Beta T Cells.
What are the two subpopulations of Alpha Beta T cells ?
CD4+ and CD8+
What are CD4 and CD8 ?
Co receptors for the TCR that facilitates the interaction of TCR with the MHC complex on the antigen presenting cell
Can mature Alpha Beta T cells express CD4 and CD8 ?
They express one or the other but not both.
What cells express CD4+
Helper T cells
What does CD4 bind ?
CD4 binds to MHC Class 2 molecules.
What is the function of a helper T cell ?
Helper T cells produce cytokines and procide help to B cells as well as stumulate cells of the innate immune system to increase their activity.
What cells express CD8 ?
CD8 cells are expressed on Killa T Cells
What molecules does CD8 bind?
CD8 molecules bind to MHC class 1
Describe the structure of CD8 molecules
Heterodimer formed by an Alpha and a Beta chain that are connected by a disulfide.
What is CD3
CD3 complex is expressed on all T cells and serves as the signal transduction unit for the TCR
What purpose do accessory molecules serve?
Accessory molecules interact with proteins on antigen presenting cells and or target cells leading to either
- Activation of the T cell
- Tighter interaction between the T cell and the APC
- Killing of the target cell
What are the three functions of adhesion molecules ?
Lymphocyte functioning antigen
CD2
Very Late Antigen
What are Lymphokine receptors?
T cells express many of these receptors so that they can respond to the lymphokines produced by other cells that help to regulate T cell functions.
How do lymphokine receptors function?
Lymphokine receptors function to activare protein kinase cascades that deliver signals to the nucleus of the T cell.
Describe the structure of the thymus
The Thymus is an encapsulated bilobed organ . Each lobe is separated by into distince lobules by trabeculae connected to a sinus beneath the capsule
What is each lobe of the thymus separated into?
A cortex and a medulla
What does the cortex consist of ?
The cortex is densely packed with thymocytes and a network of epithelial cells called cortical epithelial cells.
What do cortical epithelial cells in the thymus express?
MHC Class 2 and MHC Class 1 antigens.
What is the medulla of the thymus contain?
The medulla is populated with medullary epithelial cells, dendritic cells, and macrophages.
When is the thymus fully developed?
At birth
What is a T Cell Receptor (TCR) ?
A disulfide linked heterodimer that consists of either an alpha and a beta chain or a gamma and a delta chain.
**Most are Alpha Beta
Describe the structure of the chains that compose the T cell receptor.
Both chains haev a constant and a variable region representing the Ab molecule.
Where is the hinge region and what does it do?
The extreme end of the carboxyterminal region.
This region anchors the molecule in the membrane of the T cell and allows some flexibility of the molecule.
How are the variable regions of the TCR chains constructed?
It is constructed from a cassette of genes similar to the variable region of the antibody variable chain.
What does the variability offer the TCR ?
The ability to recognize a huge number of antigens .
What are the two lineages of T cells that are generated in the Thymus?
Alpha Beta T cells and Gamma Delta T cells.
What are the T cell co-receptors that facilitate the interaction of TCR with the MHC complex on the antigen-presenting cell ?
Can T cells express both of these on their surface?
CD4 and CD8. T cells express one of these but not both.
What cells express CD4? And what molecules interact with CD4 presenting cells?
CD4 is present on helper T cells and CD4 binds weakly to MHC 2 molecules.
What is the function of CD4 helper T cells?
Helper T cells produce cytokines and provide help to B cells as well as stimulate cells of the innate immune system to increase their activity.
What cells express CD8? What does CD8 bind? And is the function of CD8 T cells?
Cytotoxic Killer Cells express CD8, It binds MHC-1. CD8 cells kill cells that are presenting their cognate peptide antigen via MHC class 1.
What is the CD3 complex?
CD3 is expressed on all T cells and serves as a signal transduction unit for the TCR. This protein is integral to the T cell activation.
What do accessory molecules do?
Accessory molecules interact with proteins on antigen-presenting cells and or target cells leading to either 1. Activation of the T cell 2. Tighter interaction between the T cella nd the APC 3. Killing of the target cell.
What do adhesion molecules do?
The primary function of adhesion moleculesis to strengthen the interaction between a T cell and antigen presenting cells or target cells.
What do lymphokine receptors do?
T cells express many of these receptors so that they can respond to the lymphokines produced by other cells that help ro regulate T cell functions. Lymphokine receptors function to activate protein kinase cascades that deliver signals to the nucleus of the T cell.
What are the two regions of the thymus?
Cortex and Medulla
What type of cells are found in the cortex?
Thymocytes scattered macrophages and cortical epithelial cells.
What type fo cells are found in the medulla?
The medulla is populated with medullary epithelial cells, dendritic cells and macrophages.
When is T cell production in the Thymus greatest?
Right before puberty. After puberty the thymus begins to shrink because new T cells are not required to mantain T cell mediated immunity.
What are T cell precursors called?
Thymocytes
Describe positive selection for thymocyte maturation.
Positive selection for T cells with TCR that can bind to self-MHC occurs in the cortex NON-BINDERS UNDERGO APOPTOSIS
Describe negative selection for thermocyte maturation.
Negative selection for T cells that bind to tightly to self MHC+ self peptid eoccurs in the Medulla.
How are the apoptotic thymocytes killed off?
Via tingible body macrophages.
How do tingible body macrophages work?
Tingible body macrophages: cortical thymus macrophages have distinct stainign pattern due to the chromatic material of the phagocytosed thymocytes that were not positively selected and underwent apoptosis.
What are the most important markers for thymocyte development?
CD4 and CD8
If the TCR binds to MHC-2 what will the thymocyte become?
CD4+
If the TCR binds to MHC-1 what will the thymocyte become?
CD8+
Where does the CD8 CD4 selection process take place?
At or near the cortico-medullary junction.
It would be detrimental for an organism to have T cells that recognize self antigens, Where does this specificity get determined during T cell maturation?
In the Thymus.
Which MHC molecule do the thymic epithelium cells express?
MHC-1 and MHC-2, Cells that Bind MHC are allowed to continue to mature.
What is the purpose of negative selection?
To remove cells that bind self antigen
What is the autoimmune regulator?
A transcription factor expresseed in the epithelial cells of the medullary region of the thymus.
What does the autoimmne regulator do?
The autoimmune regulator causes the expression of several hundred host specific proteins by a subset of epithelial cells in the medullary region of the thymus. Their expression makes them available for uptake by medullary Antigen Presenting Cells.
What are the two regions of the Aplha and Beta chains that make up the TCR?
A and B chains have a single (V) variable region and a single (C) conserved region.
How is the variable region of the alpha segment transcribed and translated?
The variable region is produced by rearrangement of a V gene segment and a J gene segment.
How is the variable region of the Beta chain transcribed and translated?
The Beta chain coding region is produced by rearrangement of a V region gene segment, a D gene segment, and a J gene segment.
How is the TCR alpha chain rearranged?
Similiar to light chain Ig
- A V segment is joined to a J segment to produce a VJ junction. RNA is transcribed.
- The RNA is processed and splicing places the VJ junction with the Calpha region gene segment.
- The RNA is translated.
How is the TCR beta chain rearranged?
Similiar to Heavy Chain Ig
- One of the two D gene segments is joined to the J gene segment to form the DJ junction.
- A V gene segment joins the DJ junction forming the VDJ junction. Transcription takes place.
- RNA splicing removes intronic sequences and joins the VDJ junction with the C region gene segment. Translation takes place.
