36 Questions
Where do T-cells primarily mature?
Thymus
Which cells in the thymus play a crucial role in guiding T-cell development?
Thymic epithelial cells
What process allows T-cells to recognize antigens presented via HLA?
Positive selection
What happens to T-cells with TCRs that bind self-antigens with high affinity?
Undergo negative selection
Which of the following is NOT a characteristic of the thymus?
Surrounded by a thick capsule
In T-cell development, where do lymphoid progenitors divide under the influence of IL-7?
Bone marrow
What is the main characteristic that differentiates T-cell development from B-cell development in terms of maturation location?
Maturation in thymus
Where are double negative 3 (DN3) cells mostly found during T-cell development in the thymus?
In the cortex
What happens if a developing T-cell in the thymus has a useless beta chain of the TCR?
The cell dies
What is the phenotype of a developing T-cell immediately after both TCR chains have been recombined?
Double positive (DP)
What happens if a DP (double positive) cell in the thymus interacts with thymic epithelial cells expressing self-antigens with very low affinity?
Death of the DP cell
What is the consequence when DP cells interact with thymic epithelial cells expressing self-antigens with high affinity?
Death of the DP cell
What is the fate of DN cells that do not rearrange their beta chain correctly in the thymus?
Death of the DN cell
What happens to a DP T-cell with 'low-medium' affinity for a thymic epithelial cell's HLA bound to self antigen during positive selection?
It is allowed to survive
What happens to a DP T-cell with 'high' affinity for a thymic epithelial cell's HLA bound to self antigen during negative selection?
It is killed
What happens to some T-cells that recognize self during negative selection?
They become regulatory T-cells
What determines whether a DP cell expresses CD4 or CD8 co-receptor after surviving positive and negative selection?
Interaction with medullary TECs
During positive selection, what leads to a DP T-cell being allowed to survive?
'Low-medium' affinity for thymic epithelial cell's HLA bound to self antigen
What provides the driving force for lymph to enter lymph capillaries?
All of the above
Which duct drains the right arm, thoracic region, and right head/neck into the blood system?
Right lymphatic duct
What happens to external pressure when lymph enters lymph capillaries?
It dissipates
What is the role of trunks in the lymphatic system?
Combine vessels after exiting lymph nodes
During T-cell development, beta chain of the TCR is shuffled before the alpha chain
True
95% of T-cells do not survive positive and negative selection
True
Choice of CD8 or CD4 receptors occurs in the cortex of the thymus
False
Where does central tolerance occur?
Thymus
What are the consequences of defects in AIRE gene?
Autoimmune diseases
Which of the following is the major polarizing cytokine for T-reg cells?
TGF-B
What happens when CD28 of Th cell binds to B7 (CD80/86) of CD4+ T-reg cells?
Apoptosis of T-reg cell
CTLA-4 is expressed on Th cells. Which ligand of the T-reg cell does it bind to with high affinity?
B7 (CD80/86)
Which of the following receptors is expressed on T-reg cells in high levels?
IL-2R
Which of the following antibodies plays a role in maintaining barrier integrity against microbial invasion?
IgA
Which of the following diseases is associated with deficiencies in both the IL-2R-alpha gene and the CTLA-4 gene?
Type 1 DM (diabetes mellitus)
Which of the following is true regarding the spleen?
All of the above
Which of the following signals do B-cells need to be activated without the help of Th cells?
All of the above
Where does the thoracic duct drain into?
Left subclavian vein and left internal jugular
Study Notes
T-Cell Maturation and Development
- T-cells primarily mature in the thymus.
- Thymic epithelial cells play a crucial role in guiding T-cell development.
- T-cells recognize antigens through a process that involves the interaction with Human Leukocyte Antigen (HLA).
Affinity and Selection
- T-cells with TCRs that bind self-antigens with high affinity typically undergo apoptosis (negative selection).
- Characteristics of the thymus include its role in T-cell development, while a lack of lymphatic drainage is NOT a characteristic.
- Lymphoid progenitors divide under the influence of IL-7 in the thymus.
Differences in T-Cell and B-Cell Development
- T-cell maturation occurs in the thymus, whereas B-cells mature in the bone marrow.
Development Stages in Thymus
- Double negative 3 (DN3) cells are found in the thymus during T-cell development, particularly in the subcapsular zone.
- Developing T-cells with a useless beta chain of the TCR typically fail to progress in development.
- After TCR chain recombination, a developing T-cell is termed a double positive (DP) T-cell.
Positive and Negative Selection Outcomes
- DP cells interacting with self-antigens at low affinity survive positive selection.
- High affinity interactions result in apoptosis during negative selection.
- DN cells not correctly rearranging their beta chain will be eliminated.
Co-Receptor Expression and Selection Processes
- The expression of CD4 or CD8 co-receptors in a DP cell is determined by the type of TCR and selection outcome.
- DP T-cells survive positive selection through weak interactions with thymic epithelial cells.
Lymphatic System
- The driving force for lymph entry into capillaries is the pressure gradient.
- The right lymphatic duct drains lymph from the right arm, thoracic region, and right head/neck into the bloodstream.
- When lymph enters capillaries, external pressure decreases.
Functions of Lymphatic Trunks
- Trunks in the lymphatic system serve as major conduits for draining lymph and transporting immune cells.
Central Tolerance and AIRE Gene
- Central tolerance, where self-reactive T-cells are eliminated, occurs in the thymus.
- Defects in the AIRE gene lead to autoimmunity due to impaired negative selection.
T-Cell Regulation and Signaling
- The major polarizing cytokine for T-reg cells is IL-2.
- Binding of CD28 on Th cells to B7 (CD80/86) on T-reg cells enhances regulation.
- CTLA-4 binds to CD80/86 with high affinity on T-reg cells.
Immune Response and Antibody Function
- T-reg cells express high levels of CD25.
- Antibodies such as IgA contribute to maintaining barrier integrity against pathogens.
- Combined deficiencies in IL-2R-alpha and CTLA-4 genes can lead to severe immune dysfunction.
Spleen and B-Cell Activation
- The spleen plays a key role in filtering blood and activating immune responses.
- B-cells can be activated without Th cells through direct antigen recognition and signal transduction.
Lymphatic Drainage
- The thoracic duct drains lymph into the venous system at the junction of the left subclavian and internal jugular veins.
Learn about the mechanisms of positive and negative selection in T-cell development. Understand how T-cells with varying affinities for self antigens survive or are eliminated in the thymus.
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