Chapter 9 Thymus derived T cells. Flashcards
What do T cell precursors differentiate into?
immunocompetent T cells in the thymus,
Then they populate the peripheral lymphoid organs and tissues
T cells make up ___ of recirculating pool of small lymphocytes?
80%
How long can T cells live?
They are relatively long lived cells that may survive from 6 months to over 20 years
What does a developing T cell acquire in the thymus?
antigen specific receptors and other functional phenotypic characteristics that mark it as a mature T cell.
Mature T cells express a variety of cell surface proteins. Among them are proteins involved in?
- ) Antigen recognition
- ) signal transduction
- ) adhesion to APC and target cells
Activation of a cell surface receptor requires binding of ….?
binding to its specific ligand, which may be a counter receptor on another cell or a soluble protein ( cytokine)
What are Accessory Molecules?
they are cell membrane proteins which play a critical role in T cell response to antigen. Some are adhesion molecules, others deliver signals to the T cell that function with signals from the TCR-CD3/zeta zeta complex, to fully activate the T cell.
What do CD4 and CD8 molecules do?
they promote adhesion of Tcells to APCs and Target cells and also play a role in signal transduction, thereby potentiating T cell activation.
Where is CD4 molecules found?
on helper T cells. It binds to the Beta 2 domain of the class II MHC molecules on the surface of professional APCs
Where is CD8 molecules found?
on Cytotoxic T cells. It function is the recognition of the Alpha 3 domain of class 1 MHC, enabling cytotoxic cells to bind to target cells.
What do Lymphocyte adhearence molecules do?
they strengthen interactions between helper T cells and professional APCs or cytotoxic T cells and Target cells.
What does CD11aCD18 do?
binds T cells to CD54 molecules (ICAM -1) on APCs and target cells. Promotes the binding of T cells to endothelial cells during T cell extravasation.
What does CD2 (LFA-2) do?
found on mature T cells. CD2 binds to a protein called CD58 (LFA-3) present on APCs and Target cells. CD2 functions both as an intercellular adhesion molecule and as a T cell signal transducer.
T/F?
CD28 is a constitutively expressed membrane receptor for co- stimulatory signals (Signal -1)
FALSE BITCHES- SIGNAL-2
CD28 is a constitutively expressed membrane receptor for co- stimulatory signals (Signal -2) . Its ligand is B7-1 (CD80) and B7-2 (CD86) cell surface proteins that are expressed on professional APCs.
Who delivers signal 1?
the TCR complex
what is TCR alpha Beta and what kind of tail do they have?
they are integral membrane proteins with an extracellular domain, a transmembrane domain, and a short cytoplasmic tail
Where do the CDRs reside on the TCR alpha Beta?
in the variable regions
What CDR displays the most diversity on the TCR Alpha Beta chain?
CDR3- its in the center and displayes the most diversity it is a product of junctional diversity. and directly interacts with antigenic peptide, while CDR1 ( interacts with both peptide and MHC) and CDR2 (Interacts with MHC)
What is a superantigens and where can they bind?
a super antigen is are soluble bacteria proteins which bind simultaneously to all TCRS bearing certain specific Vβ domains –( No need for antigen processing)
and they bind to the Beta chain on the V domain which has the CDR4
what does clonotypic mean?
recognize only a single epitope on an MHC protein.
TCRs are clonotypic
What does allelic exclusion control?
the genetic expression of TCRs.
Who regulates the rearrangement of TCrR gene segments and BCR gene segments
several enzymes collectively called recombinases.
RAG 1 and RAG 2 are only found where?
in T and B lymphocytes, they are only active in developing lymphocytes, which explains why TCR rearrangement do not continue in mature T and B cells that have completed gene rearrangements.
How is DNA repair enzymes different from RAG proteins?
these enzymes are expressed in many cell types.
their role in Immunoglobulin (BCR) gene recombination is to repair the double stranded breaks made by RAG
What does the lack of DNA repair enzymes result in?
SCID
FIGURE OUT BETA CHAIN REARRANGEMENT ON YOUR OWN!
B chain is first followed by alpha chains. multiple variable region genes, diversity region genes and joining region genes occur at the TCR Beta locus.
Junctional diversity contributes to the generation of what CDR?
CDR 3
Name the 3 things that happen in junctional diversity?
- ) Base deletions- removal of a few bases from the broke ends of the coding sequences by endonucelases.
- ) P-nucleotides- when genes are cleaved, the ends may be cleaved asymmetrically so that one DNA strand is shorter than the other.
- ) N-region nucleotide addition- removal of up to 10 nucleotides then add them to the other end.
T/F
once rearranged in the thymus, the coding sequence of each TCR remains unchanged and does not display somatic hypermutation as with B cell derived BCRS
TRUE
When a TCR binds an antigen who sends the signal to initiate its response?
the cytoplasmic tail of the TCR is to small to transduce a signal, therefore the biochemical signals for T cell activation do not come from the TCR, but rather from the CD3 complex and Zeta Zeta chains
What do mutations in the CD3 genes do?
they effectively prevent T cell expression of TCRs
Where is thymocyte selection carried out?
in the cortex by thymic stromal cells, these cells express MHCI and MHCII
What is positive selection?
Thymocytes who have moderate affinity for self MHC molecules are rescued from programmed cell death. This ensures that mature T cells are self MHC restricted, CD4–> MHCII
CD8–> MHCI
What is Negative selection?
Thymocytes whos TCRs have low affinity or high affinity for self MHC molecules are eliminated by apoptosis. Death by apoptosis does not elicit an inflammatory response or trigger host defense mechanisms.
Who takes up cellular debris from apoptosis?
Macrophages
Where does Positive and negative selection of thymocytes (pre- T cells) happen?
in the thymus.
What are TCR gamma delta receptors expressed on?
expressed on a subset of T cells that are found mostly in epithelial locations, intraepithelial lymphocytes.
What do Helper T cells do?
Help B cells produce antibodies to protein antigens (Th CD4+)
What do Cytotoxic T cells do?
(Tc, CD8+) cause lysis of antigen bearing target cells.
How do Helper T cells play a major role in promoting innate and adaptive immune responses?
by releasing soluble helper factors ( cytokines)
Helper T cells respond only to______?
processed antigen when it is presented by professional APCs in association with self MHC class II molecules.
What signals do Naïve Th cells require for activation?
TCR complex and CD 4 recognition of peptide MHC complexes on the APC (signal 1) and co-stimulation, the scond signal (CD 28- B7-1)
What APC is the most potent activators of naïve Th cells?
Mature dendritic cells, because they always express MHC molecules and co-stimulators.
What are B7 proteins?
(B7-1, CD80; B7-2,CD86) best characterized costimulators for naïve Th cells. They are absent or expressed at low levels on resting APCs.
What is CD28?
The T cell receptor for B7 proteins. This signal enhances several Th cell responses to antigen, including the production of cytokines such as IL-2 and differentiation of naïve T cell into effector cells and memory cells.
IL-1 is a major costimulator of what?
Th2 cells (Th1 cells lack IL-1 receptors and do not respond to IL-1)
What does IL-6 promote?
promotes IL-2 and IL-2 Receptor production and T cell proliferation.
Antigen recognition of Helper T cell induces the expression of what? and what does it do?
Expression of CD40L. CD40L binds to CD40 on the APC and stimulates the expression of B7 molecules which bind to CD28 on the helper T cell and the secretion of cytokines that activate the helper T cell.
Th cells make IL-2 and IL2 receptors. If IL 2R and IL2 are bound what happens?
the cell undergoes clonal expansion.
Terminally differentiated effector Th cells enter circulation and are carried to where?
to peripheral tissues. Here they are triggered to effector function by encountering MHC peptide complexes on APCs
Do effector Th cells require two signals for activation?
No effector Th cells are more sensitive to TCR/CD4 recognition of peptide MHC complexes (Signal 1) and therefore have no need for costimulation signal 2.
Because of this effector Th cells can respond to MHC complexes on APCs that lack Co-stim. B 7 molecule.
What is the result of effector Th cell activation?
the synthesis of various membrane bound (CD40L) or secreted (cytokines) effector molecules.
CD40L binds to who?
CD40 on macrophages and B cells and activates them.
What are the three types of effector T cells?
CD4 Th1 and Th2 and CD8 T cell
are memory Th cells long lived?
yes. The expanded clone of antigen specific memory Th cells account for the increased and accelerated secondary response on subsequent exposure to the same antigen.
Normally they are functionally inactive until reexposure.
Effector T cells and Memory T cells prefer to be where in the body?
Inflamed peripheral tissues where they are needed to eliminate antigens in the effector phases of adaptive immune responses.
Effector T cells down regulate the expression of _____ and _____ and up regulate the expression of ______ and _______ and ______.
down regulate- L-selectin and CCR7
upregulate- CCR10 and LFA-1 and VLA-4 allowing them to bind to ICAM-1 and VCAM-1
Helper T cells are subdivided into Th1 helper cells and Th2 helper cells based on….?
their production of and responses to specific cytokines.
Th1 and Th2 develop from the same naïve CD4 t lymphocyte in the peripheral lymphoid organs.
what does IL-4 do?
promotes the production of the Th2 promoting transcription factor, GATA-3
IL-4 is produced in response to?
Helminth parasites and other pathogens, causes proliferating CD4 cells to differentiate into Th2 cells.
Cytokines produced by the Th1 and Th2 subsets exhibit________?
Cross regulation- cytokines from Th1 cells can block the production and or activity of the cytokines secreted by Th2 cells and vice versa.
