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149 Cards in this Set
- Front
- Back
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To fully activate a T Cell, what is required? One word.
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Costimulation
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What are the two related proteins expressed on APC's in response to a microbe?
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B7-1 and B7-2
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What are B7-1 and B7-2?
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related proteins expressed on APC's (ie., dendritic cell's) in response to a microbe.
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What is the receptor on T cell's for the B7 molecule called?
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CD28
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Where is CD28 located?
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T cell's (receptor for B7 molecules).
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True or False?
Without CD28-B7 interaction, T cell's CAN STILL become activated? |
False. CD28-B7 interaction doesn't occur, T-Cell's DO NOT become activated.
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What two protein's are expressed on APC's when MICROBES (not foreign molecules) are present?
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B7-1 and B7-2
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When does the MHC/TCR interaction occur?
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When microbe's are detected.
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What is it called when an APC (antigen presenting cell, ie., dendritic cell) is activated by a microbe?
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Innate Immune Response
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On APC's, on top of expression of costimulators, what else is secreted once APC has become activated?
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cytokines; IL-12
-also, IL-2 causes T Cell proliferation and differentation |
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What has to be present on a APC before a naive T cell will respond?
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B7 protein
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Besides the B7:CD28 interaction, what is another set of molecules involved in costimulation of T cells?
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CD40:CD40L
*CD40L = CD40 Ligand |
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Does CD40 and CD40L directly enhance T cell activation?
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No; not directly.
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Binding of CD40L on the antigen stimulates T cell's to bind CD40 on what?
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APC's
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What is IL-12 responsible for?
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enhance T cell differentation
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What leads to more expression of B7 on APCs and secretion of cytokines?
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Binding of CD40L on antigen, which stimulates T cells to bind CD40 on APCs
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CD40/CD40L binding leads to APCs that are better equiped at stimulating _________?
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T cells
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What two components must a vaccine have in order to elicit a T cell response?
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protein antigen and an adjuvant
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____________ are substances that mimic microbes in order to stimulate APCs into producing cytokines that activate T cells?
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Adjuvants
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What is an adjuvant?
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substance that mimics microbe/s in order to stimulate APCs into producing cytokines that activate T cells.
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List an example of an adjuvant?
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flagellin protein (part of microbes tail used for mobility).
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How many signals are needed from a vaccine in order for a T cell to become activated?
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two
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Blocking or enhancing T cell ____________ could be used in treatment of certain diseases?
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costimulation
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Currently, agents that block ___:____ interaction are used as treatment in such diseases as rheumatoid arthritis and other inflammatory diseases.
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B7:CD28
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What is used to BLOCK the CD40:CD40L interaction? This is important in treating inflammatory diseases and transplant/graft rejection.
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Antibodies
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Stimulation of __________ T cells could be used in treating tumors?
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specific
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What can occur is T cell response is not limited?
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autoimmune disease
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What is the purpose of having inhibitory molecules to T cell proliferation?
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If T cell proliferation is not limited, autoimmune diseases can occur.
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____________ _____________ are needed to keep the amount of T cell proliferation to the correct number?
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inhibitory molecules (such as CTLA-4, inhibitory receptor on T cells).
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What family of proteins is CTLA-4 included in?
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CD28 family (CTLA-4 is a inhibitory receptor on T cells)
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CTLA-4, a inhibitory receptor on T cells (part of the CD28 family of proteins) recognizes what on APCs?
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B7
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CTLA-4:B7 has the opposite effect as what other interaction?
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CD28:B7
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What interaction has the OPPOSITE effect as the CD28:B7 interaction?
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CTLA-4:B7
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Where is CTLA-4 expressed?
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Activated T cells
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What is "unclear" about the TWO signals of T cells?
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How it's possible to have one signal leading to activation (CD28:B7) and another leading to inhibition (CTLA-4:B7) in a T cell.
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What is the function of CD3?
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signal transduction by TCR complex.
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What is the function of Zeta?
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signal transduction by TCR complex.
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What is the ligand for CD4?
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Class II MHC
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What is the function of CD4?
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signal transduction
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What cell is CD4 expressed on? Not T helper cells!
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APCs
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What is function of CD8?
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signal transduction.
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What ligand does CD8 bind to?
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Class I MHC
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What cell is CD8 expressed on?
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APCs, CTL target cells.
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What is the function of CD28?
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signal transduction (COSTIMULATION)
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What is the ligand for CD28?
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B7-1 and B7-2
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What cell is CD28 expressed on?
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APCs
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What is the function of CTLA-4?
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signal transduction (negative/inhibitory regulation)
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Which T cell accessory molecule's function is the inhibitory regulation of signal transduction?
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CTLA-4
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What cell/cell's is/are CTLA-4 expressed on?
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APCs
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Which T cell accessory molecule's function is to serve as a costiumlator via signal transduction?
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CD28
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Which T cell accessory molecule binds to the Class I MHC molecule?
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CD8
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Which T cell accessory molecule binds to the Class II MHC molecule?
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CD4
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Where is the CD3 expressed on?
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Nowhere; along with Zeta.
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What is the name for the ligand which binds with Zeta?
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There is no ligand which binds with Zeta.
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What is the name of the ligand that binds with CD3?
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There is no ligand which binds with CD3.
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What is the function of the T Cell accessory molecule LFA-1?
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adhesion
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Which T cell accessory molecule's function is to act as an adhesion molecule?
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LFA-1
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What is the ligand for LFA-1?
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ICAM-1
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Where is LFA-1 expressed?
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APCs and endothelium
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What T cell accessory molecule is expressed on APCs and endothelium?
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LFA-1
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What are the TWO special circumstances for CD8+ T cells?
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1. often MHC-I/peptide presented on APCs is cross-presented from virally infected cells.
2. differentiation into CTLs may require CD4+ T cells to be activated at the SAME TIME. |
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In one of the two special circumstances for activation of CD8+ T cells, MHC-I/peptide presented on APCs is cross-presented from what type of cell?
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Virally infected cells.
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Differentiation into CTLs may require __________ cells to be activated at the same time?
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CD4+ T cells
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What is theorized that CD4+ helper T cells secrete in order for stimulation of CD8+ T cells?
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cytokines
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A given _____ can present a antigen by MHC-I and by MHC-II at the same time?
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APC
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What two things can an APC (ie., dendritic cell) present an antigen with at the same time?
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MHC-I and MHC-II
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True/False.
MHC-I and MHC-II can be presented at the SAME TIME by a given APC, therefore making BOTH CD4+ and CD8+ T cell's activated together? |
True.
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Both ______ & _______ can recognize an antigen (which has been phagocytosed) on a APC's surface.
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CD4+ and CD8+ T cells
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Bringing together multiple _______ (aka cross-linking) initiates signaling pathways in the cell.
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TCRs (T cell receptors)
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What is it called when TCRs are brought together? Also, what does this allow to happen in the cell?
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Cross-linking; it initiates signaling pathways in the cell
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At the point of cell-to-cell contact between T cell & APC, proteins are rearranged into a what?
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specific order
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In the biochemical pathway of activation, TCR complex, CD4/CD8, and CD28 are moved to the ________ of the cell, and ___________ form a ring around them?
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middle, integrins
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In the biochemical pathway of activation, at the point of cell-to-cell contact between T cell and APC, what are the THREE proteins rearranged in specific order (the three that are moved to the MIDDLE of the cell for integrins to form a ring around them)?
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1. TCR complex
2. CD4/CD8 3. CD28 |
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What forms a ring around TCR complex, CD4/CD8, and CD28 as they are moved toward the middle of the cell during the biochemical pathway of activation?
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integrins
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What is the term for TCR complex, CD4/CD8, and CD28 moving to the middle of the cell and integrins forming a ring around them?
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Immunologic synapse
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What is a immunologic synapse?
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During biochemical pathway of activation, multiple TCRs initiates sinaling pathways in the cell when they are brought closer together (called cross-linking). When the point of cell-to-cell contact between T cell and APC, proteins are rearranged in very specific order; TCR complex, CD4/CD8, and CD28 are moved to middle and the cell and integrins form a ring around them.
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The immunologic synapse is thought to _____________ activation of the T cell?
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optimize
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What is thought to optimize activation of the T cell?
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immunologic synapse
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During immunolgic synapse, cytokines secreted are kept in the synapse and concentrated toward what?
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APC
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During biochemical pathways of activation, much intracellular signaling occurs via adding or removing ___________ groups from one molecule/motif by activity of __________?
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phosphate, kinases
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What is one of the main ways cells use intracellular signaling?
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Adding or removing highly charged (PO4 3-) phosphates groups from molecules.
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What is the benefit of adding/removing phosphate groups from molecules (in terms of biochemical pathway activation)?
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allows for intracellular signaling to occur between cells.
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Clustering of CD4/CD8 coreceptors leads to activity of a protein tyrosine kinase called what?
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Lck
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What is need to be clustered together in order for the protein tyrosine kinase to have activity?
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CD4/CD8 coreceptors
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Clustering of CD4/CD8 coreceptors leads to activity of what?
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Lck (protein tyrosine kinase_
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Lck phosphorylates or dephosphorylates tyrosine residues?
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phosphorylates
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Lck phosphorylates tyrosine residues in motifs called what?
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ITAMs (immunoreceptor tyrosine-based activation motifs)
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What does Lck phosphorylate (specifically)?
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tyrosine residues in motifs (ITAMs)
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Where are ITAMs found?
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CD3 and Zeta
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What structure is found in CD3 and Zeta?
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ITAMs (immunoreceptor tyrosine-based activation motifs)
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What are the 3 transcription factors that become activated by adapter proteins?
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1. NFAT
2. NF-kB 3. AP-1 |
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What 4 things do the transcription factors lead to the production of?
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1. cytokines
2.cytokine receptors 3. cell cycle inducers 4. effector molecules |
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What is the cell mediated immune response mediated by? Cell?
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T cells
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Cell-mediated immunity combats infections by what?
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intracellular microbes
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What are the 2 ways microbes infect cells?
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1. phagocytosis
2. interaction with cell receptors |
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In phagocytosis, where does the microbe live?
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inside the vesicles
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During what process does the microbe stop fusion of vesicle and lysosome?
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phagocytosis
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What happens during phagocytosis?
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microbe lives in vesicle; microbe stops fusion of vesicle and lysosome.
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When microbes interact with cell receptors, where does this occur or where inside the cell does the microbe grow?
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cytoplasm
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List 2 microbes that interact with cell receptors?
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1. virus
2. some protozoa |
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Are protozoa examples of phagocytotic or non-phagocytotic microbes?
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both
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List one of the three examples provided in the diagram for phagocyotised intracellular bacteria?
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1. mycobacteria
2.Listeria monocytogenes 3. Legionella pneumonphila |
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List 3 examples of phagocytised intracellular microbes (general classes, there where 3).
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1. intracellular bacteria
2. fungi 3. protozoa |
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What is a cell in the body that would be classified as a non-phaocytised cell?
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epithelial cell
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What type of microbe infects nonphagocytic cells?
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viruses, rickettsiae, and protozoa
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Which cell must interact with a T cell before activated?
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APCs
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T cells in the lymph nodes are ________ but ________.
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mature, naive
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T lymphocytes can recognize antigen on the MHC. Have they seen it yet though?
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No
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What do T lymphocytes become once activated?
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effector cells
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Once ____ __________ is received, T cells proliferates and begins effector functions.
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two signals
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What is the two-signal hypothesis?
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1. T cell interacts with peptide antigen presented by MHC on APC.
2. microbial products or molecules from APC interact with cell surface receptors. |
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Once activated, T cell (CD8+ or CD4+) begin to secrete what substance?
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cytokines
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What is the term for when activated T cells begin secreting cytokines?
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clonal expansion
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Some T cells can travel to site of ___________ _____________.
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initial infection
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Although some T cells travel to site of initial infection, other stay in lymph nodes to serve what purpose?
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eliminate infected APCs
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_____________ (besides T cells inside lymph nodes) activate APCs to eliminate infected cells?
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cyokines
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Which lives longer, effector T cells or Memory T cells?
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Memory T cells
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Memory T cells can circulate for how long in the body?
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months to years
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Memory T cells are functionally ___________.
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inactive
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Which T cell response is quicker, first or second?
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second, Memory cells are ready to respond to repeat exposure from microbe.
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_____________ cell are eliminated as microbial threat lessens?
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Effector
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There are too many cells for huge __________ _____________ to be maintained.
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clonal expansion
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During antigen recognition and costimulation, the initiation of T cell response requires multiple ___________ interactions?
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receptor
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For initiation of T cell response, multiple receptor interactions are required, what are some of these?
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1. MHC to TCR
2. CD4/CD8 to MHC 3. Costimulatory molecules (recieve second signal) 4. Adhesion molecules (strengthen APC-T cell interaction) |
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What purpose does the costimulatroy molecules serve during T cell antigen recognition?
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recieve second signal
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What molecule strenthens the APC-T cell interaction during antigen recognition and costimulation?
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adhesion molecules
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The 4 receptor interactions during antigen recognition and costimulation serve to do what major overall purpose?
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increase intracellular signaling
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What is the FIRST cytokine produced by CD4+ T helper cells? And how may hours after activation before they start production?
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IL-2
1-2 hours |
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What cytokine stimulates survival and proliferation of T cells?
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IL-2
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What is another name synonymous with "T Cell Growth Factor"?
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IL-2
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How many CHAINS does the low affinity IL-2R receptor have?
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2 chains
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In IL-2R, there are 2 chains that make up the low affinity receptor. What does the activation of the third chain lead to?
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production of high affinity receptor
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What molecule does IL-2 bind STRONGLY with?
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ACTIVATED T cells (often one's that secrete it)
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The high affinity receptor for IL-2 is a ________-chain molecule?
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3
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Naive T cells express _____ signaling chains of the IL-2 receptor?
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2; wouldn't this explain why Naive T cell's DOES NOT bind with high affinity to IL-2. It's receptor (on naive T cells) is missing the 3rd chain.
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What TWO things are required for T cell activation?
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antigen & costimulator
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Binding of IL-2 to a T cell receptor initiates ____________ of the T cells that recognized the antigen on the APC.
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proliferation
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On activation by antigen recognition and costimulation, the cells produce IL-2 and express the ______ chain of the IL-2R, which associates with the _______ and gamma C chians to form the high-affinity IL-2 receptor.
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alpha, beta
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Within 1-2 days of T cell activation, T cells begin to what?
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Proliferate
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For CD8+; initially there is how many lymphocytes?
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1 in 10^5 or 10^6
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At the peak of an infection and proliferation, what % of ALL lymphocytes in the body will be specific for that virus?
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10-20%
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For CD4+; there is a _____-to______ fold increase in numbers.
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100-1000 fold increase
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Which group of T cells (CD4+ or CD8+) proliferate more?
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CD8+ (1 in 10^5-10^6 compared to 100-1000 fold increase)
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Often cells specific for not more than _______ immunodominat epitopes account for the large increase in cell #?
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5
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________ _____________ of T cells is almost completely from cells specific for the microbe.
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Clonal expansion
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How many days AFTER microbe exposure do differentiated effector cells leave the lymph nodes and migrate to the site of infection?
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3-4
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When do CD4+ and CD8+ effector cells have different functions?
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once they reach the site of infection.
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What is the MOST IMPORTANT cell surface protein for effector function of CD4+ cells?
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CD40L
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CD40L interacts with CD40 on what 3 cells?
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macrophages
DCs B cells |
