(Section B: Immunology) Lecture 15: T-Cell Immunity II Flashcards
Describe:
Route taken by developing T Cells
- Start at Corticomedullary Junction
- Goes into cortex
- Goes into medulla
- Finishes at Corticomedullary
What happens during T Cell development in the Thymus?
- TCR genes are recombined to generate T cells with diverse repertoire of TCRs
- T cells w/ TCRs that can recognize MHC molecules are positively selected
- T cells w/ TCRs that recognize MHC + peptide with high affinity are negatively selected
What is the outcome of T Cell Development in Thymus?
T cells are generated with TCRs ready to be activated by MHC molecules associated with nonself peptides
What are the gene loci of TCR?
- Alpha
- Beta
- Delta
- Gamma
What is the order of rearrangement for TCR genes?
- TCR beta rearranges first
- TCR alpha rearranges second
What is needed to form pre-T receptor?
Pre-T alpha and other proteins pairing together
The proteins together form what kind of complex?
CD3 complex
What are the phases in T-Cell development?
- Double Negative
- Double Positive
- Single Positive
What explains the variable region amino acid diversity?
T-cell receptor alpha and beta gene rearrangement
What are the 4 main steps of T cell development?
- TCR Beta chain rearrangement
- Beta selection
- TCR Alpha chain rearrangement
- Positive selection
TCR Beta chain rearrangement
If successful (chance of it not being successful):
* Forms Pre-TCR
* Signals for Beta selection
Beta Selection
- Stops additional TCR beta chain rearrangement
- Stimulates proliferation
- Stimulates expression of CD4 and CD8 coreceptors
- TCR alpha chain rearrangement
What also happens during beta selection?
Pre-TCR signalling
TCR alpha chain rearrangement
Results in:
* Mature TCR Immature signaling
* Negative selection for high affinity due to costimulation
Positive selection
- Selects for intermediate affinity costimulation
- Selection is by MHC-I or MHC II
What happens in mature TCR?
Mature TCR Mature Signalling
* Proliferation
* Effector function (CD4+/CD8+)
How are CD4+/CD8+ cells selected in the Cortex?
- 90-96% have no interaction, results in death by neglect
- 2-5% have high affinity interaction, results in negative selection
- 2-5% have low/intermediate affinity interaction, results in positive selection
What cells are responsible for selection in cortex?
cTEC
* Cortex Thymic Epithelial Cells
How are CD4+/CD8+ cells selected in the medulla?
- Cells are negatively selected
- Surviving ones have already differentiated into CD4+/CD8+ cells when crossing to the medulla
What cells participate in selection in the medulla?
mTEC
* Medulla Thymic Epithelial Cells
Macrophages (Dendritic cells etc.)
What is special about mTEC cells?
Contains AIRE (turns certain genes on, self antigens)
T Cell Tolerance Induction
- 90-96% Low affinity for self - Death by neglect
- 2-5% Intermediate affinity for self - Survive
- Less than 1% High affinity for self - Turn to T regulatory cells
- 2-5% Very high affinity for self - Deleted
What are T Cells activated by in the Lymph Nodes?
Dendritic Cells in the T Cell Zones of the lymph node
What happens why T Cells are activated?
Differentiate into effector cells and leave the lymph node to travel to infected tissue
How many signals do TCRs need for activation? What are they?
3
1. TCR binding to antigen/MHC
2. Costimulatory receptors
3. Cytokines
True or False:
T Cells only need 2 out of 3 signals for activation
False, all three must be present for full activation
How can dendritic cells activate both CD4 and CD8 T Cells?
By Cross Presentation of Antigen on MHC I and MHC II
How does T Cell Tolerance Induction work?
Anergy
* Lack of costimulatory receptor (non-APC cell) fails to activate T-cell
* Anergic T-cell continues through circulation without activity
What happens to the T Cell in T Cell Activation?
- Induces metabolic changes (prepares the T cell for cell division and differentiation into effector cells)
- Activates genes
- Differentiate into effectors (Th and Tc cells)
What is the purpose of cytotoxic T Cells (CD8+)?
Effectors that kill virus-infected cells
Describe:
Killing Mechanism of CD8+ cells
- CTL approaches Target Cell
- Initial contact
- Granules congregate to CTL/Target Cell contact
- More granules, target cell death begins
What is the killing mechanism of CD8+ cells?
- Using perforin to punch holes in the membrane
- Releasing Granzyme B to cause apoptosis
What is essential in the clearing of virus infections?
- IFN-alpha and IFN-beta are produced first after viral infection
- Cytokine release, a wave of NK cells follows
- Virus eliminated when virus-specific T cells finish killing virus infected cells
True or False:
Most CD8+ effector cells have long lives
False, most effector CD8+ cells have short half-lives
What happens to the surviving pathogen-specific T-cells?
Memory Cells
* 35% of circulating T Cells in a healthy young adult
* 60% in individuals over 70 years old
How does HIV work?
Infects CD4+ T cells and kills them
* Results in severe immunodeficiency (AIDS), infection, and potentially death
