Week 12 Flashcards
(75 cards)
Where do T cells develop?
In the thymus
Where is the thymus situated?
Upper anterior thorax
What are the four key regions of the thymic lobule involved in T cell development?
Corticomedullary junction (CMJ)
Cortex
Sub capsular zone
Medulla
Give brief overview of the stages on thymic development
Progenitor cells migrate into thymic parenchyma Double negative selection Become double positive cells Negative selection Positive selection Differentiate into single positive CD4+ or CD8+ cells Central tolerance Mature thymocytes re-enter vasculature
Entry of progenitor cells into the CMJ is regulated by what?
Adhesive interactions by PSGL1 on progenitor cells and P-selectin on thymic epithelium cells
(PSGL1 = platelet selecting protein ligand 1)
What is the first stage of T cell development once the progenitor cells have entered the thymus?
Double negative selection
Which chemokines regulate migration of the DN thymocytes to the outer region of the cortex?
CXCR4 - CXCL12
CCR7 - CCL19
further migration CCR9 - CCL25
During the DN migration, what happens to the thymocytes?
Begin to assemble a pre-TCR complex
Formation of the pre-TCR complex leads to which 3 things?
Initiation of proliferation
Signalling for thymocytes to become double positive (have both CD4 and CD8)
Signalling for completion of TCR complex
DP thymocytes developed in the outer space are ______
Dp thymocytes developed in the outer space are MOTILE
What are DP thymocytes able to do?
Interact with MHC complexes on cortical thymic epithelial cells via their TCR
Interaction of DP thymocyte TCRs with cortical thymic epithelial cell MHC complexes leads to what?
Positive and negative selection
What happens in negative selection of T cells?
High-affinity signals –> deletion of thymocytes by apoptosis
No signals from TCR –> death by neglect
What happens in the positive selection of thymocytes?
DP thymocytes are induced to receive signals for survival via low affinity interactions
Thymocytes which successfully survive positive and negative selection do what?
Gain expression of CCR7
Differentiate into single positive CD4+ or CD8+ cells
Once thymocytes have differentiated into single positive cells, where do they migrate to and roughly how long do they spend there?
The medulla, 12 days
Once thymocytes have differentiated into single positive cells, what is the final selection stage they undergo?
Central tolerance
Describe central tolerance
Occurs in the medulla
DCs display self Ags provided to them by AIRE+ mTECs
-ve selection - Tissue specific Ag reactive T cells are deleted
+ve selection - Treg cells generated
Generally, in which part of the thymus are the immature thymocytes found in?
Cortex
Generally, which part of the thymus are the mature thymocytes in?
Medulla
How many classes of TCR are there?
2
What are the two classes of TCR?
⍺β (majority -95%)
λδ
Which TCR class is found in the majority of T cells?
⍺β (≈95%)
In T cell activation, APCs deliver 3 kinds of signals to naive T cells. What are they?
1 - activation. Recognition of MHC complex
2 - survival. B7-CD28 co-stimulation
3 - differentiation. Production of cytokines by the APCs which will dictate the functional profile of the T cell
