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94 Cards in this Set
- Front
- Back
Pre-B-cell receptor surrogate chain is made out of? Each represents what in the actual BCR?
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VpreB = variable region of surrogate
λ5 = constant region of surrogate |
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What does IL-7 do when/where is it needed in B-cell development?
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B cells at later stage of maturation require interleukin-7 (IL-7) to stimulate their growth and proliferation
IL-7 is a cytokine that acts on late pro and pre-bcells |
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VDJ = heavy → happens first → during _________ stages
VJ = light → happens second → during _________ stage |
VDJ = heavy → happens first → during both pro-bcell stages
VJ = light → happens second → during small pre-bcell stage |
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Immature B cells vs. Mature B cells, are there differences?
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Imature: IgM > IgD
Mature: IgD > IgM |
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Lareg Pre-B cells → Small Pre-B cell, what significant happens or is formed at this point in B-Cell maturation?
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Large pre-bcells have successfully rearranged the heavy chain, express μ-chain, and begin rearranging light chain
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D + J of heavy chain rearrangement signifies what stage in b cell?
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early pro bcell
successful rearrangement moves on to late pro bcell |
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V + (DJ) of heavy chain rearrangement signifies what stage in b cell?
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late pro bcell
successful rearrangement moves on to large prebcell |
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checkpoint one in bcells?
checkpoint two? |
pre-b-cell receptor = checkpoint 1
full b-cell receptor = checkpoint 2 |
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Type 1 B-cells?
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CD5 B-cells = Type 1 B-cells = B1 cells → not as specific = polyspecificity
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Burkitt's lymphoma:
the ____ gene on chromosome ___ is translocated next to the ____ gene on chromosome ____ |
MYC (chr8) is a cell division gene → placed next to Ig gene (chr14) after translocation → tons of abnormal growth
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Primary location of CD5 b-cells?
Are they replaced from bone marrow? Need T-cell help? |
CD5 bcells are basically the opposite:
located in peritoneum and pleural area self replicating (not replaced) and dont need tcell help |
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RAG1 and 2 are expressed first during ______ through _______
Turned off during large pre-bcell stage and turned back on during ______ |
Expressed first: During early pro through large pre-B
Expressed second: during small pre-bcell phase to rearrange light chain |
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CCL21 is secreted by_____ and binds to ______ in order to_____
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CCL21- secreted by stromal cells to get bcells through HEV
CCR7 = receptor on bcell for CCL21 |
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CCL19
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secreted by dendritic cells to attract bcells
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CXCL13 – secreted by______ in order to?
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secreted by FDC to get bcells in to follicle
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BAFF stands for? secreted by?
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B-cell activating factor – promotes survival of B-cell
Receptor is on B-cell; cytokine secreted by a lot of cells |
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LT
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mediates FDC network
Receptor of same name is on FDC; made by b-cell |
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in germinal center activated b-cells become large proliferating lymphoblasts called _______ → those mature into slower dividng bcells called _______
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centroblasts
centrocytes |
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centroblasts are in the _____ zone and centrocytes are in the _____ zone
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o Centrocytes in the LIGHT zone
o Centroblasts in the DARK zone |
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What are in the light and dark zones of the germinal center?
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dark zone has centroblasts, both have b-cells, the rest is in light zone
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Plasma cells can differentiate directly from ?
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activated B cells; from isotype switched, somatically hypermutated centrocytes; or from memory B cells
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What are the isotypes of the light chains and which is usually rearranged first?
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Kappa and Lambda → Kappa is rearranged first
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What makes up the pre-TCR
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CD3: ε+δ and ε+ϒ
ζ chains pTα |
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Notch1?
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Influences cells to become T-cells
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IL-7
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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
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Deletion in chromosome 22 in which the thymus fails to develop and T cells are absent
Susceptibility to wide range of opportunistic infections → resembles SCID (severe combined immunodeficiency disease) |
DiGeorge’s syndrome
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What chromosome has a deletion in DiGeorge’s syndrome?
symptoms represent? |
chr. 22
SCID = symptoms of the pathogen |
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Double negative T-cell?
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no cd4 or cd8
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Which takes place first positive or negative selection? Where does positive occur?
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positive then negative
positive is in the thymic cortex |
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11. If you are heterozygous for MHC (HLA) genes how many presenting MHC (HLA) molecules do you have?
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12
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Which type of TCR predominates alpha beta or gamma delta?
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Αβ
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Rearrangement of a beta-chain, how many attempts do they have to make a functional rearrangement?
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4 gene rearrangements
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When are the CD- 4 and 8 co-expressed, before or after beta chain rearrangement?
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After beta chain rearrangement
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The Tcell becomes permissive for alpha chain rearrangement; stimulates CD4 and CD8 expression; stimulates proliferation; and stops beta chain rearrangement when?
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the pre-TCR is successful
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Autoimmune Regulator (AIRE)
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Causes the expression of tissue specific proteins (ie proteins only found in the pancreas)
Allows to test for self-reactions for more than what’s normally in the thymus |
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Does the thymus play a role in activation of naive T cells? If not, where do the T cells meet their antigen?
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No, they are activated in secondary lymphoid tissues.
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Where does central tolerance for T-cells take place?
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Thymus medulla
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A regulatory T-cell is a CD-4 or CD-8 T-cell? What transcription factor is unique to the T-reg cells?
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• CD4
• FoxP3 |
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Homing:
L-selectin is on the ____ and binds to ____ LFA-1 is on the _____ and binds to _____ |
L-selectin is on the T-cell and binds to vasuclar adressins (glycam)
LFA-1 is on the T-cell and binds to ICAM-1 |
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The T-cells will migrate toward the high concentrations of _____ and ______ within the lymph node
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The T-cells will migrate toward the high concentrations of CCL21 and CCL19 within the lymph node
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What is S1P? What does it do?
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sphingosine 1-phosphate attract t-cells that HAVENT met their antigen back into circulation
When t-cells meet their antigen in nodes they suppress S1P receptors |
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What t-cells migrate to infection?
What tcells stay in the lymph? |
CD8 and TH1 migrate
TH2 stays |
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B7 molecules?
What binds to B7 to activate Tcells? |
co-stimulatory molecules present on professional APCs
CD28 |
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What is CTLA-4 what does it bind to and what is the result of it binding?
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CTLA-4 is a B7 receptor on Activated t-cells. Binding to B7 slows down activation and limits cell proliferation
B7 binding to CD28 activates a T cell, while B7 binding to CTLA-4 slows down activation and limits cell proliferation |
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What chemokine directs and niave T-cells to the T-cells area to check the dendritic cells MHC molecules?
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CCL18
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What happens when a naïve T cell interacts with an antigen presented by a cell that is not a professional antigen presenting cell
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It becomes anergic = no IL2
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IL-2?
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produced by activated tcells that is essential for their proliferation
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What does a Professional APC have that other cells don’t have?
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the co-stimulatory molecule B7
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Langerhan’s cells what and where are they?
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Langerhans’ cell of the skin is a typical immature dendritic cell with large granules (Birbeck granules = phagosome like form)
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Mature vs Immature dendritic cells molecules?
functions? |
DEC 205 = immature dendritic cell
DC SIGN = mature dendritic cell Immature = capture Mature = present to t-cells |
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16. What does IL-2 do and when is it made?
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IL-2 binds IL-2 receptors of T cell to drive clonal expansion of the activated cell
made when tcell is activated |
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DAG leads to ______
IP3 _____ and activates _____ |
DAG leads to the NFkB and AP1 transcription factors
IP3 increases calbium and activates the transcription factor NFAT |
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What is ZAP 70 and when is it activated (which cell type and when?)
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ZAP 70 is attached to CD3 on t-cells and leads to activation when MHC:peptide and coreceptor are bound
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What cells in B7 on? What cell is CD28 on? What do they do when they come together?
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•B7 is on all professional antigen presenting cells
•CD28 is on T-cells •Together they cause cell proliferation by the signal transduction. •They bind to each other and activate NFAT → production of IL-2 → proliferation |
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Where in the lymph node are dendritic cells?
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in the cortical T-cell areas of the lymph node.
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Where in the lymph node are macrophages?
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throughout the cortex and medulla
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Where in the lymph node are Bcells?
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the lymphoid follicles in the cortex
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Do CD8 T-cells use cytotoxins or cytokines? CD4?
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CD8 = both
CD4 = cytokines |
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CD8 cytotoxins?
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Perforin and granulysin make pores in the target cell membrane for the granzymes to enter and cleave certain cell proteins
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Fas and FasL? location and function?
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Fas:FasL interaction sends a signal to the target cell to undergo apoptosis.
FasL is on the lymphocyte (tcell) → Fas is on target cell |
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Main pathway to get rid of unwanted lymphocytes?
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Fas and FasL
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VLA4 is expressed on the _________ and binds to VCAM-1 on the _______
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VLA4 is expressed on the activated t-cell and binds to VCAM-1 on the infected endotheium
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_____ is expressed on the activated t-cell and binds to _____ on the infected endotheium
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VLA4 is expressed on the activated t-cell and binds to VCAM-1 on the infected endotheium
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What are VLA-4 and VCAM-1 responsible for?
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They home the t-cells to infected/inflammed tissues
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Can effector T cells be stimulated in the absence of co-stimulating signal?
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Yes once they are activated
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CD8 cells also contribute to the immune response by secreting the cytokine?
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IFN-gamma
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Functions of IFN-gamma?
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inhibits the replication of viruses
increases the processing and presentation of viral antigen by MHC class activates macrophages |
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Activation of Macrophages, What is needed? And which cells activate them?
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TH1 cells activate macrophages via Both CD40 and IFN-gamma
CD8 can also activate them via IFN gamma and carbohydrates in place of CD40 |
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Can TH1 cytokines affect Th2 differentiation and visa-versa?
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Cytokines produced by TH1 cells can suppress the differentiation of TH2 cells and Cytokines produced by TH2 cells can suppress the differentiation of TH1 cells
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What is the only cell that can activate a CD-8 T-cell without help
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Dendritic cells
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What are the other ways to get a CD8 T cell activated other than by a dendritic cell?
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Under conditions of suboptimal co-stimulation, CD4 T cells can help activated naïve CD8 T cells.
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Tuberculoid leprosy?
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controlled by TH1 biased response = cell mediated response
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Lepromatous leprosy?
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uncontrolled infection by TH2 biased response = humoral response
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Which leprosy is worse?
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Lepromatous leprosy
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ALPS is caused by what?
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Individuals who lack functional Fas molecules cannot control the size of their lymphocyte population nor remove autoimmune cells
Secondary lymphoid organs become swollen in the absence of infection |
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ALPS stands for?
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autoimmune lymphoproliferation syndrome
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Activated T-cell adds alpha chain of IL-2 receptor. IL-2 operates via _________ mechanism
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autocrine --> tcell secretes IL-2 which binds to the complete IL-2 receptor on the same T-cell
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Cytokines of the CD8 T-cell?
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IGN-gamma
LT |
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Cytokines of the CD4 TH1-cell?
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IFN-gamma
GM-CSF TNF-alpha LT IL3 |
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Cytokines of the CD4 TH2-cell?
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IL-4
IL-5 IL-10 IL-13 TGF-beta |
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What comes first for B-cells positive or negative selection?
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B cells: negative then positive
T-cells: positive then negative |
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Where does negative selection of B-cells take place? positive?
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Bcells negative selection is in the bone marrow
positive selection is in secondary lymph |
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Is there somatic recombination outside the bone marrow?
hypermutation? |
No somatic recombination in secondary tissue
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Burkitt’s lymphoma is caused by the translocation of the myc gene from chromosome 8 to the IG area on 14 of the T-cell genes, true or false
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False
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Can there be b-cell heavy chain rearrangement to save a self-reactive bcell?
Light chain? |
no heavy chain rescue
light chain rescue is possible |
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Immature B-cells enter the lymph from the ______ via the _______
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blood via the HEV
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Does b-cell isotype switching take place in marrow?
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no, only in secondary tissue
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T-cells enter the thymus via the _____
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blood
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Hassall’s corpuscle is a ?
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Hassall’s corpuscle is a death center
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Do bone marrow transplants fix DiGeorges?
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no
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Nonfunctional rearrangement of the alpha chain locus results in the t-cell.....
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undergoing apoptosis - cant use delta
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Can you have a double positive thymocyte with two different receptors?
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yes
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How do t-cells get through the endothelium?
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extravasation/diapedasis
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Is the costimulatory requirement a type of peripheral tolerance?
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yes
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