Term
| Where are naive T cells found? |
|
Definition
| blood and secondary lymphoid tissues |
|
|
Term
| What is T cell activation or T cell priming? |
|
Definition
| when naive t cells are activated by specialized antigen presenting cells that present antigen in the context of MHC I or II |
|
|
Term
| T/F The adaptive immune response is generated at the site of infection. |
|
Definition
| FALSE. Dendritic cells take the antigen to the secondary lymphoid organs where the immune response is generated |
|
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Term
| Dendritic cells in tissues are called ________ dendritic cells. |
|
Definition
|
|
Term
| What are the different ways dendritic cells take up antigens to present them via MHC class II? |
|
Definition
| receptor-mediated endocytosis and macropinocytosis (which is nonspecific and not mediated by a receptor) |
|
|
Term
| What are the different ways dendritic cells obtain antigen particles to present them via MHC class I? |
|
Definition
| viral infection, cross-presentation after phagocytic or macropinocytic uptake, and transfer from incomming dendritic cell to resident dendritic cell (viruses are presented in these ways) |
|
|
Term
| From what type of vessels do T cells enter a lymph node? What part of the lymph node do they enter? |
|
Definition
high endothelial venules or afferent lymph vessels
the cortex of the lymph node |
|
|
Term
| How do naive T cells leave lymph nodes? |
|
Definition
| efferent lymph if it hasn't seen its antigen |
|
|
Term
| T/F Naive T cells undergo apoptosis within weeks if they have not met their antigen. |
|
Definition
| FALSE, they live for years |
|
|
Term
| How do naive T cells "know" to go to the secondary lymph tissue once they leave the thymus? |
|
Definition
| they "home" in response to concentration gradient of the chemokines CCL21 and CL19 bound to the surface of HEV and produced by stromal cells and dendritic cells in the lymph node cortex. They bind these chemokines via CCR7 |
|
|
Term
| Where are L-selectins found and what do they bind to? |
|
Definition
| found on various leukocytes and bind to carbohydrates on endothelium to initiate leukocyte-endothelial interaction |
|
|
Term
| Where are mucin-like vascular adddressins found and what do they bind to? |
|
Definition
| found on endothelium, HEV, and mucosal lymphoid tissue venules and bind to L-selectin to initiate leukocyte-endothelial interaction |
|
|
Term
| Where are integrins found and what do they bind to? |
|
Definition
| found on various leukocytes and bind to cell adhesion molecules and extracellular matrix for strong adhesion |
|
|
Term
| What role do some immunoglobulin superfamily members play in cell adhesion? |
|
Definition
| they are expressed on T cells and are a target for integrins |
|
|
Term
| What receptor/ligands allow naive T and B cells to roll along HEV? |
|
Definition
| L selectin on T/B cell binds to GlyCAM-1 and CD 34 on HEV |
|
|
Term
|
Definition
| LFA-1 is on B and T cells. It is "activated" by chemokines when T/B cell is rolling along HEV. When it is activated LFA-1 binds tightly to ICAM-1 initiating diapediesis |
|
|
Term
| What are the two "homing receptors" of naive T cells? (aka what receptors guide T cells specifically to secondary lymphoid tissue?) |
|
Definition
|
|
Term
| A naive T cell binds a dendritic cell through what interactions? |
|
Definition
| TCR (with CD8 or CD4) and MHC/antigen. But a second co-stimulatory signal is required for successful T cell activation. Ex. is B7 on activated dendritic cell binds to CD28 on naive T cell |
|
|
Term
| What happens after B7 on dendritic cell binds to CD 28 on T cell? |
|
Definition
| T cell is activated and the nexpresses CTLA-4 which binds to B7 with higher affenity |
|
|
Term
| Compare and contrast the functions of CD28 and CTLA-4. |
|
Definition
| Both are receptors on T cells that bind B7 on dendritic cells. However, CD28 activates the immune response while CTLA-4 dampens the immune response. |
|
|
Term
| Which of the three antigen presenting cells is the "most potent"? |
|
Definition
|
|
Term
| What are langerhans cells? |
|
Definition
| specialized dendritic cells in the skin and some other stratified epithelia |
|
|
Term
| What are mature dendritic cells in secondary lymphoid tissue sometimes called? |
|
Definition
| interdigitating reticular cells |
|
|
Term
| T/F All of the professional antigen presenting cells can activate naive T cells. |
|
Definition
| FALSE. Only dendritic cells and macrophages. B cells do not usually participate in the activation of naive T cells. |
|
|
Term
| Where in the lymph node are dendritic cells located? |
|
Definition
|
|
Term
| Where in the lymph node are B cells located? |
|
Definition
|
|
Term
| Where in the lymph node are macrophages located? |
|
Definition
|
|
Term
| Is MHC expression the same for dendritic cells in peripheral tissue and dendritic cells in lymphoid tissue? |
|
Definition
| NO, there is more MHC expression on dendritic cells in lymhpoid tissue |
|
|
Term
| T/F MHC expression on macrophages is constitutive. |
|
Definition
| FALSE, it is induced by bacteria and cytokines |
|
|
Term
| T/F MHC expression on B cells is consitutive. |
|
Definition
| True but it increases upon activation |
|
|
Term
| On what APC is costimulator delivery constitutive? |
|
Definition
|
|
Term
| Which APC is found only in lymphoid tissue, connective tissue, and body cavities? |
|
Definition
|
|
Term
| Which APC is found in only in lymphoid tissue and peripheral blood? |
|
Definition
|
|
Term
| What is the region of contact between a T cell and an APC called? |
|
Definition
|
|
Term
| How does the clustering of receptors in the immunological synapse between T cell and APC cause the activation of ZAP-70? |
|
Definition
| activation of associated kinases such as Fyn which leads to phosphorylation of ITAMs in cytoplasmic tails of CD3 protein.CD4/8 binding to MHC brings kinase Lck to phosphorylate/activate ZAP70 which is bound to phosphorylated ITAM |
|
|
Term
|
Definition
| activation of PLCgamma which causes DAG and IP3 apthways. These pathways all lead to NFkB, NFAT, and AP-1 which turn on transcription of genes that direct T cell proliferation and development of effector function. |
|
|
Term
| What is one of the most important genes that ZAP70 turns on? |
|
Definition
| IL-2, because it drives proliferation and differentiation of activated T cells |
|
|
Term
| How does IL-2 discriminate between naive T cells and activated T cells? |
|
Definition
| naive T cells express the low-affinity receptor for IL-2 while activated t cells express the high affinity receptor for IL2 |
|
|
Term
| What is the mechanism of the drug cyclosporin A (cyclosporine)? |
|
Definition
| disrupts TCR signaling to prevent IL-2 production and thereby immunosuppress the patient |
|
|
Term
| What is the mechanism of the drug tacrolimus (FK506)? |
|
Definition
| disrupts TCR signaling to inhibit IL-2 production and immunosuppress the patient |
|
|
Term
| What is the mechanism of the drug rapamycin? |
|
Definition
| inhibits signaling from the IL-2 receptor to immunosupress a patient |
|
|
Term
| THe IL-2 receptor alpha chain is also known as _____. |
|
Definition
|
|
Term
| What happens to naive T cells that recognize an antigen in the absence of co-stimulation? |
|
Definition
| the t cell becomes non-responsive or anergic meaning the T cell can no longer make IL-2 |
|
|
Term
| When the immune system of an individual can not respond to an antigen that person is said to be _______ to that antigen. |
|
Definition
|
|
Term
| What are the signature cytokines of TH1 cells? |
|
Definition
| IL-2 and IFNgamma (causes macrophage activation, inflammation, and production of opsonizing antibodies) |
|
|
Term
| What are the signature cytokines of TH2 cells? |
|
Definition
|
|
Term
| What are the major cytokines of Treg cells? |
|
Definition
|
|
Term
| What is the major cytokine of TH17 cells? |
|
Definition
| they produce IL-17 and promote proinflammatory responses praticularaly the influx of neutrophils in the mucosa (may play a role in autoimmunity) |
|
|
Term
| Which cytokines cause the different differentiation pathways of CD4 Tcells? |
|
Definition
| TGF-beta>Treg. IL-12 and IFN-gamma> TH1. IL-4>TH2 |
|
|
Term
| TH1 cell development is first stimulated by what cytokines made by which cells? |
|
Definition
| IL-12 from dendritic cells and macrophages and IFN"gamma" by NK cells. This causes production of transcription factor called T-bet which turns on IFNgamma and t cell is commited to being a TH1 |
|
|
Term
| What happens to CD4 T cells when IL-4 binds to IL-4 receptor? |
|
Definition
| transcription factor GATA-3 is produced which makes IL4 and IL5 and commits cell to TH2 lineage |
|
|
Term
| T/F In sub-optimal costimulatory conditions, CD4 T cells can help activate naive CD8 T cells. |
|
Definition
| true. to do this however, CD8 and CD4 must recognize antigen on the same APC. CD4 helps by making IL-2 or other cytokines. |
|
|
Term
| Why might it be advantageous to require strong co-stimulation for activation of CD8 cells? |
|
Definition
| CD8 cells can induce a lot of tissue damage so you want to make sure an infection is really going on before you activate them |
|
|
Term
| Where do T cells go once they've been activated? |
|
Definition
| CD8s and most CD4 TH1 enter the blood to seek out sites of infection. CD4 TH2 cells stay in the lymph nodes. |
|
|
Term
| How do activated T cells leave the lymph node? |
|
Definition
| they loose L-selectin and CCR7 and start expressing VLA-4 (alpha4 integrin) which binds to VCAM-1 on inflammed blood vessel endothelium. Effector cells also increase expression of CD2 and LFA-1 so they can interact with any cell |
|
|
Term
| T/F Only APCs express B7. |
|
Definition
|
|
Term
| T/F Activated/Effector T cells still need a co-stimulation signal when they bind peptide-MHC complex. |
|
Definition
|
|
Term
| JAKS stands for _______. Where are JAKs found? |
|
Definition
| Janus Kinases. THey are found bound to the cytoplasmic domain of cytokine receptors |
|
|
Term
| What happens when a cytokine binds a cytokine receptor? |
|
Definition
| ctyokine binding causes the two receptors to dimerize. The two cytoplasmic JAKS activate/phosphorylate each other. Transcription factors called STATS are phosphorylated/activated by JAKS. STATS dimmerize and go to nucleus to initiate gene transcription |
|
|
Term
| What are the cytotoxins and cytokines produced by CD8 cells? |
|
Definition
| cytotoxins (perforin, granzymes and granulysin) and cytokines (IFN-gamma, LT) |
|
|
Term
| What are teh cytokines produced by TH1 cells? |
|
Definition
| IFN-gamma, GM-CSF, TNF-alpa, LT, IL-3 |
|
|
Term
| What are the cytokines produced by TH2 cells? |
|
Definition
| IL-4, IL-5, IL-10, IL-13, and TGF-beta |
|
|
Term
| When do CD8 T cells start making cytotoxins? |
|
Definition
| as soon as they meet the antigen in secondary lymphoid tissues |
|
|
Term
| How do CTLs (cytotoxic T cells)induce infected cells to undergo apoptosis? |
|
Definition
| via release of cytotixins (perforin an granzymes) and via Fas-ligand which binds to Fas on infected cell |
|
|
Term
| Fas is a member of the ________ receptor family. |
|
Definition
|
|
Term
| For how many days do T cells undergo clonal expansion after they are activated? |
|
Definition
|
|
Term
| How do we get rid of excess effector T cells when there is cessation of antigenic stimulus? |
|
Definition
| T cells undergo apoptosis induced by Fas-Fas L ligation |
|
|
Term
| T/F Fas-Fas L interaction is the main route lymphocytes are killed off during lymphocyte development |
|
Definition
|
|
Term
| Individuals that lack functional Fas molecules develop a disease called ____________. |
|
Definition
| Autoimmune lymphoproliferative syndrome (ALPS) (usually caused by an inheritance of one nonfunctional copy of Fas gene) |
|
|
Term
| What might you find on physical exam of a child with ALPS? |
|
Definition
| lymphadenopathy and splenomegally |
|
|
Term
| What would blood work of a patient with ALPS look like? |
|
Definition
| elevated serum Igs, increased B cells and large number of double negativ T cells. |
|
|
Term
| What would you use to determine whether a patient had ALPS or a malignancy? |
|
Definition
| chromosomal abnormalities or oligoclonal T cell expansion would predict malignancy and be uncharacteristic of ALPS |
|
|
Term
|
Definition
| anti-inflammatory corticosteroid prednisone with immunosuppressant drug cyclosporin A |
|
|
Term
| T/F ALPS patients are succeptible to B and T cell lymphomas. |
|
Definition
|
|
Term
| What are the two signals macrophages need from CD4s to become activated? |
|
Definition
| a primary signal from IFN-gamma and a second signal delivered by CD40 ligand on T cell binding to CD40 on macrophage |
|
|
Term
| What happens to macrophages once they are activated? |
|
Definition
| increase expression of MHC class II and B7 which increases antigen presentation to naive T cells |
|
|
Term
| When do CD4 cells make effector molecules? |
|
Definition
| "on demand" which takes several hours |
|
|
Term
| How do TH2 cells prevent macrophages from producing too much microbicidal substances that can be harmful to tissues? |
|
Definition
| characteristics cytokines (TGF-beta, IL-4, IL-10, and IL-13) which inhibit macrophage activation |
|
|
Term
| TH1 cell secretes IFN-gamma and CD40 ligand to... |
|
Definition
| activate macrophage to destroy engulfed bacteria |
|
|
Term
| Activated TH1 cell secretes FAS ligand or LT to.. |
|
Definition
| kills crhonicall infected macrophages, releasing bacteria to be destroyed by healthy macrophages |
|
|
Term
| Activated TH1 cell secretes IL-2 to |
|
Definition
| induce T cell proliferation |
|
|
Term
| activated TH1 cell produces IL-3 and GM-CSF in order to... |
|
Definition
| induce macrophage differentiation in the bone marrow |
|
|
Term
| Activated Th1 cell produces TNF-alpha and LT in order to |
|
Definition
| activate endothelium to induce macrophage adhesion and exit from blood vessel at site of infection |
|
|
Term
| Activated TH1 cell produces CXCL2 in order to... |
|
Definition
| cause macrophages to accumulate at site of infection |
|
|
Term
| Under what conditions do granulomas form? |
|
Definition
| when intracellular pathogen successfully resists the killing activity of activated macrophages and a chronic infection accompanied by inflammation develops (characteristic of mycobacteria) |
|
|
Term
| Describe granuloma morphology. |
|
Definition
| They have a central core of infected macrophages which can include multinucleate giant cells formed by cell fusion. This central core is surrounded by large single macrophages sometimes called epitheliod cells |
|
|
Term
| What cells prevent granulomas from desseminating and killing patient? |
|
Definition
| CD4 TH1 (aids pts die from granulomas) |
|
|
Term
| T/F TH2 cells that recognize a certain antigen can activate B cells that recognize a different antigen. |
|
Definition
|
|
Term
| T/F CD4 cells that recognize one epitope can activate CD8 cells that recognize another epitope. |
|
Definition
| True, they both have to recognize the same antigen but not the same epitope of that antigen. This is called cognate interaction |
|
|
Term
| B cell becomes activated after it presents MHC II/peptide to TH2 via... |
|
Definition
| interactions between CD ligand on TH2 and CD 40 on B cells and by IL-4, IL5, and IL6 characteristically secreted by TH2 cells |
|
|
Term
| How did we make an effective haemophilus influenzae virus vaccine? |
|
Definition
| bacterial polysaccharide was covalently coupled to tetanus toxoid. In this way, the TH2 cell will recognize the tetanus toxoid and induce proliferation of memory b cells. |
|
|
Term
| A cell with high levels of CD25 (the alpha chain of the IL-2 receptor), FOX P3, and immunosuppressive anti-inflammatory cytokines (IL-4, IL-10 and TGF-beta) is a ________ cell. |
|
Definition
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