Lecture 3 C: T-Cell Development Flashcards
Where are T cells derived from?
The thymus gland
What is the purpose of positive selection in T cell development?
To ensure T cells recognize self-MHC molecules
What is an immature T-cell called?
thymocyte
Is the thymus gland considered a primary or secondary lymphatic organ?
primary
CD4 T cells are also known as _____ T cells, and CD8 T cells are also known as _______ T cells.
helper; cytotoxic
Which organs are primary lymphoid organs?
bone marrow and thymus
Which organs are secondary lymphoid organs?
lymph nodes and spleen
Of the bone marrow and thymus, which is considered the CLP (common lymphoid progenitor)?
bone marrow
What is the difference between Natural Killer Cells and CD8 (Cytotoxic) T-cells?
Cytotoxic T-cells are located in the adaptive immune system
What does the HIV virus target and destroy in T-cells?
CD4
Do immature T-cells have CD4 or CD8 glycoproteins?
Immature cells have BOTH
Do mature T-cells have CD4 or CD8 glycoproteins?
Depending on the cell type, it will have one or the other.
(T-Helper: CD4, Cytotoxic T-cell: CD8)
What are the phases of T-cell maturation/ selection?
- DN (double negative)
- DP (double positive)
- SP (single positive)
What does CD stand for?
(In CD8 and CD4)
Cluster differentiation (proteins)
What is the function of chemokines?
To attract mature B cells into the thymus
What does “MHC” stand for in MHC I and MHC II?
Major Histocompatibility Complex
When is the TCR beta chain first expressed?
At the DN (double negative), pre- T-cell stage
What stage does the complete T cell occur? (has beta and alpha chains)
At the DP (double positive)
When does a T cell become mature?
Once it has reached the single positive stage, either CD4+ or CD8+
Failure of any cell to express/present _______ _______at any stage leads to ________.
antigen receptors (TCRs); apoptosis
What functions as the checkpoints for recognizing self-antigens on the T cells?
MHC (Major Histocompatibility Complex)
What is positive selection for T cells?
The T cell must recognize the MHC without too much recognition of the self-antigen it carries.
When T cell receptors recognizes MHC I, the peptide complex loses expression of _______?
CD4
When T cell receptors recognizes MHC II, the peptide complex loses expression of _______?
CD8
Which MHC class does CD4 recognize?
MHC II
Which MHC class does CD8 recognize?
MHC I
What happens if a T cell does not recognize any MHC class?
apoptosis
Why is it bad if a double positive (DP) T cell receptor strongly recognizes MHC?
Because the peptide complexes in the thymus will undergo apoptosis.
What is the principle function of integrin?
adhesion
What is the principle function of each: CD3, CD4/CD8, and CD28?
signal transduction
What is the principle function of TCR?
specific recognition of an antigen
Why do T cell progenitors have to pass 3 major checkpoints during development?
ensure they are MHC restrictive and non auto-reactive before forming CD4+ and CD8+ T cells
What are the 3 checkpoints during T cell development?
(1) Beta selection
(2) Positive selection
(3) Negative selection
What is the function of peripheral (secondary) lymphoid organs?
They provide an environment for the initiation of adaptive immune responses to foreign antigens.
What happens during beta selection of the T cell?
Thymocytes undergo rearrangement of V/D/J gene of the beta chains. They are tested for successful rearrangement of the TCR beta.
What stage does beta selection occur?
double negative (pre-T cell)
What is the purpose of checkpoint #2 (positive selection)?
To see if the TCR alpha chain is able to function with the TCR beta chain. This is determined through the ability for the receptor to bind/recognize the self-peptide (MHC)
What is the purpose of checkpoint #3 (negative selection)?
To determine the TCR safety through its ability to bind to
self peptide-MHC on APCs with high affinity
Is positive selection an antigen-dependent process?
Yes. If not, it repeats the rearrangement of the alpha chain until death by neglect.
Why does a T-cell need both TCR alpha and TCR beta? (what do they bind to?)
TCR alpha binds to self-peptides while TCR beta binds to self-MHC
What % of thymocytes successfully become CD4+ and CD8+ T cells?
~2%
If the T-cell is antigen-dependent in the negative selection, what happens next?
clonal deletion
What are Peyer’s Patches?
gut associated lymphoid tissue (GALT)
Where do B cells develop in dogs, pigs, and ruminants? Does it last for life?
Ileal Peyer’s Patches in the intestines. Yes, lasts for life, but it shrinks in size.
(ileum is the last part of the small intestine)
What is the secondary lymphatic organ in the intestines and how long does it function?
Jejunum (2nd part of the small intestine); if lasts for life.
What is the largest lymph node in the body?
spleen
What are the T cell stages in order?
DN pro, DN pre, DP immature T cell, SP mature T Cell
Which interleukin is essential for B cell maturation and growth?
IL 7
What portions of BCR & TCR have the VDJ segments, and what portions of BCR & TCR have the VJ segments?
Heavy & Beta ; Alpha & Light
Existence of BCR & TCR specificity for only one antigen is enabled by what?
Gene rearrangement of the variable region.
At what T cell stage does VDJ recombination and RAG 1 & RAG 2 expression occur?
DN pro T cell stage
At what T cell stage does the VDJ acts on the surrogate alpha chain?
DN pre T cell stage
At what T cell stage is the alpha-chain tested on the established TCR-beta and auto-reactiveness is tested.
DP immature T cell stage
At what T cell stage is CD4 w/ MHC 2 and CD8 w/ MHC 1?
SP mature T cell stage
What causes proliferation of the DN pro T cell within the thymus?
IL 7 & thymic hormones
Which hormone is secreted back to the T cell if it fails any of the checkpoints and tests?
Fas ligand (FasL) is a cell membrane cytokine that can trigger apoptosis.
Razzle, dazzle, (FasL)
What is the only way that a T cell can recognize an antigen?
It has to be presented by an MHC molecule
What does heterodimer mean?
It is made of two chains
What percent of T cells do alpha & beta chains present? gamma & delta?
alpha & beta - 95% of TCR
gamma & delta - 5% of TCR
What stage of T cell development do mature T-cells migrate to secondary lymphatic organs?
SP (single positive)
What are the 3 types of T cells when mature?
CD4, CD8 and Regulatory T-cells
Does the TCR have any special names like Ig M, Ig D, etc?
No
Which chains for T cells contain VDJ genes?
beta and delta
Which chains for T cells contain VJ genes?
alpha and gamma
Give 2 examples of polypeptide hormones that act on the T cell in the DN stage and cause proliferation?
thymulin, thymic humoral factor
