Term
| The development of T cells in ?? |
|
Definition
| the thymus --> start out in the bone marrow (hematopoieis) --> makes lymphocye progenitor--> migrates to thymus (which directs it toward Tcell differentiation -to rearrange its TCR genes) |
|
|
Term
| What is the positive selection of T-cell? Negative selection? |
|
Definition
Tcell receptors that actually recognize your MHC molecules will be selected as positive (to be kept alive cuz default path is apoptosis)
-Negative selection: get rid of Tcells with TCRs that bind too strongly and can create an autoimmune problem |
|
|
Term
| Similarities in the development of T and B lymphocytes: |
|
Definition
-Derive from bone marrow stem cells
-Undergo gene rearrangement --> antigen receptors
--B cells rearrange in the bone marrow
--Precursors of T cells leave the bone marrow ->thymus
-Junctional diversity-(P and N nucleotide additions) |
|
|
Term
| 2 distinct T cell lineages |
|
Definition
-Alpha:beta Receptors (1-2% of the primary repertoire (functional rearrangment, actually being released in system - main Tcells)
-Gamma:delta Receptors (not as stringent selection and smaller population) |
|
|
Term
| Major function of the thymus |
|
Definition
| to ensure that mature T cells that leave thymus are restricted to the particular MHC class expressed by an individual person (self -MHC) |
|
|
Term
| Two selection processes of T cells: |
|
Definition
Positive selection leads to the death of immature T cells having receptors that do not interact with any self-MHC class I and II
-Negative selection induces the death of those immature T cells that are autoreactive (receptors bind too strongly to a self-MHC molecule) |
|
|
Term
| Mature T cell leaving the thymus to circulate in the secondary lymphoid organs is: |
|
Definition
1. Rendered tolerant of self-antigens
2. Responsive to foreign antigens
3. Ready to fight infection |
|
|
Term
| Tcell progenitors develop in |
|
Definition
| the bone marrow and migrate to the thymus-->Tcell precusor rearranges its TCR genes-> pos and neg selection takes place--> sent out to secondary lymphoid tissue--> can become activated |
|
|
Term
| Immature Tcells that: recognize self MHC receive; interact with self antigen are: |
|
Definition
| signals for survival;removed from the repertoire |
|
|
Term
| during pos. selection, depending on which MHC molecule the TCR recognizes: |
|
Definition
| will determine whether it will be a CD4 or CD8 thymocyte -- while developing will be called a double positive (have both CD4 and CD8 on surface) but will change when MHC recognized. (ex. recognizes MHC I, CD4 will be pulled in and degraded and cell will become CD8 - single positive) |
|
|
Term
| Mature Tcells encounter foreign antigens in the: |
|
Definition
| peripheral lymphoid organs and are activated |
|
|
Term
| Activated Tcells proliferate and migrate into: |
|
Definition
| peripheral sites to eliminate infection |
|
|
Term
T cells originate from bone marrow stem cells (Named thymus-dependent lymphocytes --> T cells
-2 lineages develop in parallel from common precursors |
|
Definition
(Majority are alpha:beta cells; Minority are gamma:delta cells)They race
VD&J of Beta chain: alphabeta at same time of gammadelta rearrange. (Beta usually wins) When functional rearrangement --> shut off RAG 1&2 so that only one gene is expressed (allelic exclusion)--> proliferate --> turn Rag1&2 back on to rearrange alpha chain (alphabeta and gammadelta race again) |
|
|
Term
While developing in the thymus
T cells also express other cell-surface proteins related to their eventual function. Examples: |
|
Definition
| CD4 and CD8 glycoproteins |
|
|
Term
From the bone marrow, T cell precursors migrate through the blood to the thymus.
Mature T cells then leave the thymus in the blood and enter: |
|
Definition
| the secondary lymphoid organs, such as the spleen or lymph nodes. (leaves bloodstream and enters secondary lymphoid tissue through HEVs) |
|
|
Term
| In the absence of activation, mature T cells: |
|
Definition
| recirculate between the blood, the secondary lymphoid tissues, the lymph and the GALT. |
|
|
Term
Thymus is found in the upper anterior thorax above the heart
Immature T cells - called thymocytes - are embedded in epithelial cell network called the thymic stroma
Thymus is primary lymphoid organ: |
|
Definition
-Involved in the development of T cells
-Not involved in lymphocyte recirculation via lymph
-Blood is the only route through which T cells enter and exit |
|
|
Term
| In the embryonic development of thymus |
|
Definition
-Epithelial cells (stromal cells) of cortex (outer)
-Epithelial cells of medulla (inner)
-Rudimentary thymus called thymic anlage (Is colonized by cells from bone marrow) |
|
|
Term
| stages of Tcell development: |
|
Definition
-Progenitor cells -->thymocytes & dendritic cells --> populate medulla
-Bone marrow derived macrophages --> also populate medulla (also macrophages scattered throughout the cortex of thymus
-Thymocyte mature --> progressively move from outer subcapsular region to the inner cortex and the medullar |
|
|
Term
|
Definition
Bcell- 3-8 wks if not activated but continually developed throughout life
Tcell- very long lived self-renewing |
|
|
Term
|
Definition
-Example of importance for the development a functional T-cell repertoire
-A deletion in chromosome 22 in which the thymus fails to develop (mature) and T cells are absent
-Susceptibility to wide range of opportunistic infections -->resembles SCID (No T cells and no activation of B cells) |
|
|
Term
| Thymus fully developed before birth; is most active in the young; atrophies with age (Starts atrophy by ae 1)-> results |
|
Definition
-Progressively shrinks, fat gradually claiming areas once packed with thymocytes = involution of the thymus
-Reduced production of new T cells not noticeably impairing T cell immunity
(Nor does thymectomy = removal of the thymus affect T cell immunity of adults)
-Once established, the repertoire of mature peripheral T cells is long lived and/or self-renewing
(Differs from the mature B-cell = shorted lived cells that are continually being replenished from the bone marrow)Can have new Tcell development up to age 30-50 |
|
|
Term
| Maturation of thymocytes into mature T cells occurs in distinct steps: |
|
Definition
-Marked by changes in the status of the TCR genes
-Expression of the TCR protein
-Production of other T-cell surface glycoproteins
(CD4, CD8, CD3 complex)
-Changes in cell surface proteins expressed at each developmental stage is a way to distinguish between subpopulations of developing thymocytes |
|
|
Term
| -Progenitor T cells that enter the thymus lack the cell surface glycoproteins (CD4, CD8, CD3) of mature T cells but they do have |
|
Definition
CD34 (a cell surface glycoprotein of stem cells).
-The TCR genes are in germline config.
-Upon interaction with thymic stromal cells, the progenitor T cells will proliferate and differentiate
-Approximately one week later, progenitor T cells will express the T-cell specific adhesion molecule CD2 and other surface markers such as CD5 but no TCR complex |
|
|
Term
| No CD4 or CD8 on surface is called: |
|
Definition
| double negative thymocytes (have CD2, CD5 and IL-7 receptor) |
|
|
Term
| Next step in thymocyte development: |
|
Definition
-IL-7 receptor on T-cells is essential for binding IL-7 secreted by thymic stromal cells – helps tell the T-cell what to do next in its maturation.
-Notch 1 – at all stages of maturation in the thymus signals are sent through this receptor to drive the T-cell in their differentiation. |
|
|
Term
| T-cell Development in the Thymus is Driven by |
|
Definition
| the Receptor Notch 1 attaches to ligand(has intr and extra cellular domain--> can release intracellular domain into nucleus and can help Tcell go into differentiation) |
|
|
Term
| T Cells Have Two Lineages Distinguished By The Expression Of An alpha:beta Or A gamma:delta TCR. Commitment does not occur before TCR rearrangement but is a race to obtain a productive rearrangement |
|
Definition
-Thymocytes will rearrange their beta, gamma and delta-chain genes about the same time
--Different from B-cell development (recall: each type of Ig gene is rearranged in turn and in a set order) |
|
|
Term
| Productive gamma and delta-chain gene rearrangement made prior to a productive beta-chain rearrangement leads to gamma:delta receptor which signals cell to stop rearrangement of beta chain (gammadelta on surface does not require pos and neg selection - no co-receptor, just sent out - no MHC restriction - can act as BCR) But more frequently... |
|
Definition
the beta chain productively rearranges before the gamma and delta-chains.
-beta-Chain assembles with a surrogate alpha chain = ptalpha (pre-T-cell receptor) which signals the cell to halt rearrangement of beta, gamma and delta-chain genes and begin to proliferate; also has CD3 complex and zeta chains |
|
|
Term
After expression of the pre-TCR, the recombination machinery is reactivated & targeted towards the alpha chain loci (and the gamma and delta loci)
In a minority of these cells: |
|
Definition
successful completion of gammadelta chain gene rearrangements occurs before the alpha chain gene has rearranged
-In a majority of these cells, productive rearrangement of the alpha-chain gene occurs first (alhabeta Tcell)
-Recall the delta chain locus is located within the alpha-chain locus…a rearrangement at an alpha-chain locus results in the deletion of the complete delta chain locus from the chromosome |
|
|
Term
| Cells committed to one lineage can contain: |
|
Definition
| productive rearrangements for the TCR genes of the other lineage (except for alpha-chain). |
|
|
Term
| Immature T Cells That Undergo Apoptosis Are Ingested By Macrophages In The Thymic Cortex... Failure to make a productive rearrangement results in death by apoptosis (fate of about 98% of thymocytes) |
|
Definition
-Macrophages in thymus continually remove dead cells
-Apoptotic cells are scattered throughout the cortex but are rare in the medulla |
|
|
Term
Tcell maturation process checkpoint1= Pre-TCR:Beta chain, surrogate alpha chain (ptalpha), CD3 complex and zeta chains signals;
Checkpoint 2= |
|
Definition
signals to nucleus to stimulate expression of CD4 and CD8 to become dbl pos
-stop additional Beta chain arrngement (allelic exclusion) and proliferate
-start rearrangement of alpha chain after proliferation
CHeck pt2: Once alpha chain made sent to ER to make sure it can bind beta chain to TCR |
|
|
Term
-TCR beta-chain locus
-TCR alpha-chain locus has no |
|
Definition
-V,D,&J gene segments and is rearranged first (similar to heavy chain in Ig’s)
-D segments and is rearranged after the beta-chain (similar to light chain in Ig’s) |
|
|
Term
| Mature double positives have: |
|
Definition
| comlete alpha and beta chains, CD3 comlex, and zeta chains |
|
|
Term
| Production of T-cell receptor beta chain stops beta-chain rearrangement and leads to expression of CD4 and CD8 |
|
Definition
| Production of a functional beta-chain gene --> beta-chain translation and assembly with a surrogate alpha-chain (preTalpha), CD3 proteins and zeta chain to form a pre-T cell receptor --> transported to the cell surface |
|
|
Term
| Role of pre –T-cell receptor is analogous to the pre-B-cell receptor in B-cell development |
|
Definition
-Triggers the thymocyte to proliferate and halt beta-chain gene rearrangement
-Ensures only one type of T-cell receptor beta-chain is expressed by the T cell |
|
|
Term
| What gene segments are rearranged for the alpha and beta chain of T cells? |
|
Definition
Alpha= V and J (like light chain)
Beta= V,D,J (like heavy chain) |
|
|
Term
| Three diff kinds of effector Tcells and their fxns: |
|
Definition
Th1- activate macrophages
Th2- activate Bcells
Tc- tell cells (intracellular i.e. viruses) to die by apoptosis w/ release of cytotoxic granules |
|
|
Term
| Naive Tcells only have one way to get into lympnode: |
|
Definition
| HEVs (High endothelial venules)- called in by chemokine signals which can start rolling adhesion, tight binding, diapedesis, and migration. |
|
|
Term
| Tcell and dendritic cell are called into lymphnode at same time by: |
|
Definition
| CCL19 and CCL21 - puts Tcells and demdritic cells in Tcell area of lymphnode so TCRs can check dend. cells for their MHC plus peptide |
|
|
Term
| % of Tcells found in secondary lymphoid tissue (versus in the blood) |
|
Definition
| 95-98% at any given time found in secondary lymphoid tissue (meeting grounds to find antigens) |
|
|
Term
| Th1, Th2, Tc cells go out or stay in secondary lymphoid tissue once activated? |
|
Definition
Th1- go out to activate macrophages at site of infection
Th2- stay in to activae B cells (Bcells move into germinal center - which is in secondary lymphoid tissue)
Tc- go out to tell infected cells to die by apoptosis |
|
|
Term
| Niave Tcell interaction with MHC II on any type of cell other than a professional antigen presenting cell: |
|
Definition
| will lead to inactivation of that Tcell |
|
|
Term
| Macrophages: if present at site of infection- |
|
Definition
| will not be told to migrate to secondary lymphoid tissue (resident, not migratory)- dendritic cells will - but if they are already present in sec. lym. tissue can present to Tcells with MHC II |
|
|
Term
| number one antigen presenting cell |
|
Definition
| dendritic cells (because they are migratory) |
|
|
Term
| immature dendritic cells have phagocytic receptors on the surface. WHen they become mature: |
|
Definition
| They switch and pull phagocytic recetors in and put adhesion molecules plus a lot of MHC (plus peptide) on the surface (lysosomal proteins stay in center and MHC on surface) |
|
|
Term
| immature dendritic cells have phagocytic receptors on the surface. WHen they become mature: |
|
Definition
| They switch (do to chemokine environment around them telling them to mature) and pull phagocytic recetors in and put adhesion molecules (which can bind strongly to Tcells) plus a lot of MHC (plus peptide) on the surface |
|
|
Term
| We activate the primary adaptive immune resonse where? |
|
Definition
| secondary lymphoid tissue (i.e. peyer's patch, spleen, lymph nodes, GALT) |
|
|
Term
| Langerhans cells (containing lysosomal proteins and MHC) |
|
Definition
| immature dendritic cell that can take up pathogen at site of infection (phagocytic receptors on surface)- will not present |
|
|
Term
|
Definition
| pathogens, recognize them as pathogens and take them up for phagocytosis. (phagocytic receptor for immature dendritic cells) |
|
|
Term
|
Definition
| random sampling of extra cellular fluid environment (by dendritic cells) and check for pathogens - which are then processed and put on surface of MHC II- which will activate Th1 and 2 --> Th2 will activate Bcells |
|
|
Term
| Receptor mediated endocytosis, and macropinocytosis of pathogens will be |
|
Definition
|
|
Term
| viral infection of the dendritic cell - virus will replicate inside the cell and then... |
|
Definition
| proteosomes degrade petides, send through TAP1&2, into the ER, which will try the peptides against MHC I, if bind goes to surface to present to CD8 cells |
|
|
Term
|
Definition
| MHC I put up instead of MHC II (exact mechanism is unknown) |
|
|
Term
|
Definition
| a particular TCR can recognize antigen plus MHC. If you take same antigen and put it on a diff MHC molecule, TCR won't recognize because TCR must recognize both MHC (with peptide) plus antigen |
|
|
Term
| Positive selection takes place in the |
|
Definition
| cortex of the thymus and is mediated by cortical epithelial cells bearing complexes of class I and class II self-MHC and self-peptides |
|
|
Term
| At the point of contact – interactions between the alphabetaTCR of thymocytes with self-MHC and self-peptide are tested |
|
Definition
-If a peptide:MHC complex is bound by a thymocyte within 3-4 days of expressing a functional TCR, then a positive signal is delivered to the thymocyte.
-A thymocyte that does not receive a signal dies by apoptosis and is removed by macrophages. |
|
|
Term
| Self-peptides presented in the MHC molecules of cortical epithelial cells are derived from self-proteins present in the thymus. |
|
Definition
| The number of different peptides that can be presented by one individual’s MHC molecule is estimated to be about 10,000. |
|
|
Term
| Some double positive thymocytes can express |
|
Definition
| two alpha chains chains (one from maternal allele and one from the paternal allele) and thus two types of TCR and undergo positive selection by engagement of one of these receptors. |
|
|
Term
| Negative selection is mediated by several cell types, most important of which are the |
|
Definition
bone marrow-derived dendritic cells and macrophages.
(Engagement of the MHC molecule of one of these specialized thymic antigen-presenting cells by the TCR of a thymocyte causes that cell to undergo apoptosis and phagocytosis by macrophages) |
|
|
Term
|
Definition
CD25
FoxP3 a transcriptional repressor is used by the regulatory T-cells (unique to regulatory T-cells)
-Distinct from naïve T-cells
-Contact with MHC II – self-antigen can suppress proliferation of naïve T-cells responding to self-antigens
-Suppressive effects require contact between the two T-cells and secretion of non-inflammatory cytokines |
|
|
Term
| In an healthy individual there are about twice the number of |
|
Definition
CD4 T cells to CD8 T cells.
(In patients with AIDS this proportion changes becomes the AIDS virus infects and kills CD4 T cells) |
|
|
