T Lymohocytes Flashcards
What happens when immature T cells leave bone marrow?
migrate to thymus for development
What is the goal of development?
mature T cells that leave thymus have diverse receptor specificity, are tolerant to self antigen, and recognize self MHC
What are the 2 phases of T lymphocyte development?
- early phase
- second phase
What happens in the early phase?
- commitment to T-cell lineage
- gene recombination
What happens in the second phase?
- selection for cells with receptors that recognize self MHC
- selection against cells with receptors that recognize self antigen
- commitment to CD4 or CD8 lineage
How do immature T cells know how to develop?
-move through different microenvironments which provide signals for the stages of development
What do the signals for the stages of development come from?
binding receptors on cells and from cytokines
Where do immature T cells enter the thymus?
at corticomedullary junction which is between the medulla and cortex
How do immature T cells travel through thymus?
travel through cortex, finish development in medulla, before leaving thymus as mature T cells
How long does T cell development take?
1-3 weeks
T cell precursors that enter the thymus are…
double negative
What does being double negative mean?
do not express CD4 or CD8
What are the stages of the early phase?
- DN1 stage
- DN2 stage
- DN3 stage
- DN4 stage
What is the DN1 stage characterized by?
cells that have CD44
What happens during the DN1 stage?
- cells proliferate
- begin to express CD25
What is the DN2 stage characterized by?
cells with CD25 and CD44
What happens during the DN2 stage?
- recombination of TCR beta, gama, delta chains
- cells fully commit to T cell lineage
- lose expression of CD44
What is the DN3 stage characterized by?
cells with CD25
What happens in the DN3 stage?
- Beta selection
- lose expression of CD25
What is beta selection in the DN3 stage?
- cells that have successfully undergone gene recombination of beta chain have become alpha beta T cells
- remaining cells become gamma delta T cells
- cells that are selected for express pre-alpha chain
What is the DN4 stage characterized by?
cells with no CD44 or CD25
What happens in the DN4 stage?
- alpha chain recombination of TCR
- cells gain expression of CD4 and CD8 (become double positives)
What are the stages of the second phase of development?
- positive selection stage
- negative selection stage
- lineage commitment stage
What happens in the positive selection stage?
- select for cells with TCRs that bind self MHC
What is it called when you select for cells that bind self MHC?
MHC restriciton
What happens in the negative selection stage?
select against cells that strongly bind to self-antigen
What does selecting against cells that strongly bind to self-antigen?
establishes self-tolerance
What happens during the lineage commitment stage?
silencing of either CD4 or CD8 gene to have either CD4+ or CD8+
What happens at end of second phase of T cell development?
mature T cells leave thymus and enter bloodstream
What do regulatory T cells (Tregs) express?
CD4, CD25, FoxP3
Where do regulatory T cells develop and what from?
in thymus from autoreactive T cell precursors
How do Tregs dampen immune response?
- compete for cytokines with other T cells
- secrete inhibitory cytokines
- inhibit professional APCs
- kill other immune cells
What is it called when Tregs compete for cytokines with other T cells?
cytokine deprivation
How do Tregs kill other immune cells?
using perforin and granzyme
Where does T cell activation occur?
lymph nodes/ secondary lymphoid tissues
What is required for T cell activation?
- TCR complex
- adhesion molecules
- co-stimulatory receptors
What does TCR bind to? (TCR complex)
MHC/antigen
What does CD4 or CD8 on TCR complex bind to?
-CD4 binds MHC-II
_ CD8 binds MHC-1
What does CD3 on TCR complex bind to?
doesn’t bind to anything