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147 Cards in this Set
- Front
- Back
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T cells are what for immune system orchestration
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The conductor
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What is the primary cell mediated immune response
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When naïve T cells are activated in response to proliferation and differentiation into effector cells
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Windows T cell activation occur
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Peripheral lymphoid organs, activated by dendritic cells
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what are secondary – peripheral lymphoid organs
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Lymph nodes, spleen, mucosa associated lymphoid tissues (malt)
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How do dendritic cells activate T cells
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1-take up bacterial antigens in skin
2- move to enter a drainig lumph vessel 3- got o lymph node where they settle in t-cell areas 4-activate niave t-cells |
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What is activated T cell
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primed=effector=armed effector
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What is required to prime a naïve T cell
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1 t cell receptor recognitif a peptide on MHC
2 co stimulation (ex. B7 on dendritic cell |
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t of f? effector t cells require co stimulation for thier activity
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false
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what do antigen prestenting celld have
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express MHC II
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whre are dendritic cells found
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throughout the cortex of lymph nodes in the tcell area
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where are macrophages found
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thru the body, mostly in marginal sinus, and medularry cords
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where are bcells found
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mainly in the follicles
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what are the strongest activationrs of naive t cells
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dendritic cells (produce more MHCII
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what drives migration of dendritic cells to lymph nodes
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pathogen induces TLR signalin g in immature dendritic cells, and enhance antigen processing
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what does TLR signialling do to dendritic cells
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major alteratin in the chemokine receptors in DC cells
causes DC to change behavior (licensing) |
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what makes activated DC sensitive? to what? what does this do
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receptor CCR7, sensitive to CCL21(chemokine) produced by lymphoid tissue, it induces migration
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what does tlr signialling do to DC
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induces CCR7 and enhances processing of pathogen derived antigens
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Wht does CCR7 do for DC's
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directs migration into lymphoid tissues, augments co-stimulatory molecules and MHC moleclues
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what is th side effect on DC after they are considered to be mature
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no longer able to engulf antigens , now express high levels of MCH Iand II nd co stim. B7 molecules- only aft er it knows it has uptaken an antigen
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how does DC atract naive Tcells
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expresses hing levels of adhesion molecules and secret CCL18(chemokine) which specifically attracts naive tcells
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how long does it tak for DC's to activate T cells
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approx 20 hours
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do DC have to cross endothelium to raech lymphnodes
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no
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do tcells have to cross endothelium to get form blood circulation to lymp nodes
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yes
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what is the cycle of a Tcell
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1- circulates in blood
2- pass by a lympnode, migrates thru endothelium tissue into lymph 3- if not activated there will go to another lymphnode in lymnph system 4-will continue to go lymph to lymph untill end of system then return to blood |
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what allows tcells to go from blood to lymph
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chemokines CCL21 (adhesion molecules) adn Lselectin
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what allows for rolling interaction in lymph node
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binding of l selectin to GlyCam-1 and Cd34
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what holds t cells tight to enter the lymph sys
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LFA-1 to ICAM-1
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what activated LFA-1 for tcell migration to lymph
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chemokines bound to extra cellular matrix
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what is allows t cell to now patrol for infection rather than rolling adhesion (now an activater/effector tcell)
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t cell no longer produces l-selectin (stops adhesion)
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what caused effecto tcells to stop and migrate to the infection site
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CCL-8 (adhesion molecules), VLA-4 (on effector t cells), binds to VCAM-1 on (inflamed /infected tissue)
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what is considered the priming stage
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when dc's present antigens to naive tcells in lympho nodes
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wht occurs inthe priming stage btx DC and naive tcells
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transient binding of naive tcells to antigen presenting cess (ex dc) gives time for t cell to sample the many MHC on APC to presence of antigen peptides
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what are the two different kind of foreign molecules required for t cell activation by antigen presenting cells (APC)
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antigen uptake,,, engulfing, and PAMA
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waht are the three signals needed to activate a tcell
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1- binding of MHCII to the t cell receptor( and LFA-1 and ICAM-1(adhesion)
2- causes change in LFA-1 (makes stornger bond) and costim. signal btx CD28 and B7 3- CD40L induced signals APC increases B7 ecpressin and APC survival |
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how doe tcell proliferation get limited
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CTLA4 replaces CD28 and bindsmore avidly to B7, sends inhibitory signals
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what happens to tcell if there is stimulation only with out CD4 and t cell receptor interaction
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has no effect on naive t cell
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what happenes in there is only the MHC and CD$ stimulation wiht out the co stimulation
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inactivates the t cell ( inhibitits it ) (anergy)
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wha thappned when a tcell is activated
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1- proliferation ( clonal expansion
2- gains effector functions ( turns into CTL- cutotoxic tcells or TH - helper t cells |
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what does the co stimulation of activated tcells (CD28) (aka signal 2) do
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induces expressoin of tcell growth interleukin-2 and the high affininty IL2 receptor
(il2 receptor not found on non activated tcells) |
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what is another name for a naive t cell
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cd8-tcell
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what to cd8 tcells (peptide + Mhc I receptors) do
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they are cytotoxic (killer t-cells)- kill cells
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what to cd8 tcells (peptide + Mhc I receptors) do
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they are cytotoxic (killer t-cells)- kill cells
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what do cd4 tcells (peptide+MHCII) do/ become
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Th1 cell- assist in macrophage killing of engulfed bacteria
TH1 and 2- activates th2 cells to produce antibodies TH17- activates fibroblasts n epithelila cells Treg cells- inhibits imature dendritic cells |
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what do TH1 cells do
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stimulates macrophages activity
and hlpb in activating bcells and class switching in activated b cells |
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what do cd4 tcells (peptide+MHCII) do/ become
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Th1 cell- assist in macrophage killing of engulfed bacteria
TH1 and 2- activates th2 cells to produce antibodies TH17- activates fibroblasts n epithelila cells Treg cells- inhibits imature dendritic cells |
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what do TH2 cells do
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help in acitvatin b cells, and required for the switchin of b cells to produce the IgE antibody
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what do TH1 cells do
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stimulates macrophages activity
and hlpb in activating bcells and class switching in activated b cells |
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what do the variations of signal 3 do the differentiation of naive cd4 t cells
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makes them become different types of helper cells
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what do TH2 cells do
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help in acitvatin b cells, and required for the switchin of b cells to produce the IgE antibody
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what caused a naive t cell to differentiate into a cytotoxic cell
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binding of MHCI along with B7and CD28
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what do the variations of signal 3 do the differentiation of naive cd4 t cells
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makes them become different types of helper cells
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what causes a naive t cell to diff. into a TH1 cell
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3rd signal of bining with MHCII, IL-12 and IFN-y
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what causes a naive t cell to diff. to a TH2 cell
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3rd signal of MHCII , and IL 4
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what caused a naive t cell to differentiate into a cytotoxic cell
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binding of MHCI along with B& and CD28
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what causes a naive t cell to diff. into a TH1 cell
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3rd signal of binding with MHCII, IL-12 and IFN-y
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what causes a naive t cell to diff. to a TH2 cell
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3rd signal of MHCII , and IL 4
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activation of a cd8 tell makes it so it no longer needs what to kilts target
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secondary signal, cd28/b7, it only needs to recognize the presented antigen
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what 3 ways does the antigen specific t cell receptor control the delivery of effector signal
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1- tight close bond btw effector cell n target cell
2-focus delivery by reorientating the secretory app. 3- triggers the making and release of granules |
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effector molecules of effector tells fall into what 2 categories (i.e. whats released)
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1- cytotoxins (released by cd8 cytotoxic t cells
2- cytokines- released by cd4 helper t cells |
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what are the three major granules released by cytotoxic cd8 t cells
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1-perforin (aids in getting toxin thru target cell wall)
2-granzymes ( activate apoptosis once in cell) 3- granulysin (anti microbila actions and induces apoptosis) |
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what initiates apoptosis in cell
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pro-caspase-3 (inactive at first bc its bound
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what activated (unbinds caspase-3 )
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tBID unbinds it
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what induces the DNA fragmentation on the target cell
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CAD = DNAase
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Th1 cells do what to macrophages
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inorder to assist the macrophage kill its engulfed antigen it will:
increase production of enzymes, enhance phosphor /lysozome production , increase MHC i andII, maximize antigen presentation to signal other cells |
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macrophage requires what 2 signals to become activation
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1- provided by cytokine, IFN-y secreted by Th1 cells(increases production of enzymes for reps. burst, increases MHC I and II present)
2- CD40 ligand expressed by Th1 cell enhances b7 expression |
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what does expression of TNF-Alpha do in macrphages
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enhances inflamation
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whats bad about an activated macrophage releasing No and o2- extracellular
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it can cause damage outside and near self, this is done to kill antigens that may be outside around it
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INF-y and CD40 ligan in macrophage does waht
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makes cell try to kill its engulfed bacteria
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IL-2 does what which tcells
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makes them proliferate
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IL3 + GM-CSF does what in bone marrow
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causes macrophage differentiation
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TNF-a anad LT-b does what to endothelium
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activates-
to induce macrophage binding and exit from blood vessels at site of infections |
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CCL2 does what at sight of infection
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accumulate
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why will form when an intracellular pathogen can not be totally eliminated
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granuloma
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what is t cell tolerance
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lack of immune response to an antigen
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what is central tolerance
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deletion of self reactive t cells in the thymus
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what is peripheral tolerance
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deletion or control of self reactive T cells in the periphery
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what occurs with t cells for central tolerance
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those that recognize self are selected in thymus for positive selection, those that have big affinity for self and deleted int he thymus,(negative selection)
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if a peripheral t cell recognizes an antigen in absence of a co stim. what happens
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cell is inactivated
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how do t cells discriminate between self and non self peptides
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they are educated in the thymus
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why are recent thymocytes classified as double negative
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bc they express neither surface receptors CD4 or CD8
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what first occurs to a newly arrived thymocyte
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1 acted on by vdj rearranging, (beta chain), becomes double positive (has bothe surface receptors), vj rearranging(a-chain) removes one surface receptor, becomes single positive and can now interact with cortical epithelial cell
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where does thymocyte make cd4 or cd8 transition?
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in the cortex
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what happens if cotical epithelial cell can't recognize a dbl positive thymocyte
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it dies by neglect
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after cd4 or cd98 differentiation an it entered the medulla what happens in medula
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they come in contact with the medullary epithelial or dendritic cell, if the recognition is too strong to self it will be killed ( to strong of attraction means it will act against self)
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why three outcomes of t cell cross reactivity are possible
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1- strong affinity= negative selection (death)
2- weak affinity= export to periphery 3-very weak = death by neglect /failure of positive selection |
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at what part does the positive selection occur in the thymic cortex
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the double positive
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what is one of the key APC's which mediate positive selection
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cortical epithelial cells
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what interactions result in a positive selection
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low affinity interaction btw TCR and peptideMHC complex
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what causes a negative selection in the thymus
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high affinity btw TCR and MHC
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when does negative selection occur in thymic medulla or citric-medullary junction
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at the DP to SP transition
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what cells are key APC"S in the negative selection
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Medullary epithelial cells, dendritic cells and macrophages
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positive /negative selection is important why
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to tune the mature tells in periphery for self non self discrimination
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what is the important factor in determining the fate of a t cell in thymus
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affinity
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what is central tolerance
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deletion of self reactive t cells in thymus
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what makes sure the t cells won't attack self as all possibilities of self are not present in thymus
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up regulation expression of transcription factor calle AIRE, promotes promiscuous gene expressions max the variety of self peptides
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what makes up peripheral tolerance, why have it
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because central tolerance isn't 100 %.
1-ignorance - # of peptide interactions need to be high 2- anergy- when co stimulation is non present- makes cell unresponsive 3- deletion- sometimes goes apoptosis when recognizes self antigen |
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why do we have different isotopes (classes of antibodies)?
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causes them to have different physical properties allows them to adapt and function in different parts of the body
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what are the three functions of antibodies
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1- neutralization
antibody surrounding 2- opsonization engulfing 3- compliment activation uses compliment system |
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what does IgA, and IgG do , and where
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in gut and respiratory , neutralizes pathogens and their toxins in gut, also neutralizes animal venoms and viruses
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What is IgG
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1-principal antibody in blood and extra cellular fluids
2- opsonizes pathogens 3- most abundant antibody |
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how does IgG help with phagocytosis with macrophage
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IgG binds to pathogen, when those bound antibodies are then bound to the FC site on the macrophage , it induces phagocytosis, antibody alone won't do it
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what doe IgM do where are they found
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mainly found in the Blood and lymph,
helps activate the compliment system low abundance |
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how does IgM activate the compliment system
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its pantametric, binds to surface of pathogen and adopt a stable platform
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describe IgE
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high affinity for Fc receptors on mast cells, basopohils and activated eosinophils,
ice can bind to fc receptors without prior binding to pathogen |
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what cells are responsible for innate immunity
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macrophages, mast cells, granulocytes, and Nk cells
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what do mast cells do in the connective tissues
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watch out , in their cytoplasm there are large granules containing histamine and other inflammatory mediators,
they target parasites (to big to engulf) can induce muscle contractions to expel parasites form gut and airways, makes local blood vessels supply a flow of fluid and blood to flush parasites form epithelium |
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change in environmental danger signals cause macrophages to do what
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change their phenotype, and physiology.
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what activates a tissue macrophage into a microbicidial macrophage
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Th1, Nk cell,
produces IFNy and TNF |
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what rapidly converts resident macrophages into a population of cells programed to heal
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IL-4 form Th2 and granlocytes,
causes to not present antigens, lil inflammatory cytokines, secrets precursors of extra cellular matrix |
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when a Treg cell produces IL-10 to macrophage and IL-12 is reduced what happens
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makes a reg macrophage to limit inflamation
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can a reg macrophage be made back into a normal macrophage?
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yes by the presence of a pathogen
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what drives antibody switching
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Th1
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TGF-b causes naive t cells to become what
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Treg cells
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TGF-b and IL-6 causes naive t cells to become what
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Th17 cells
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IL-12 and IFN-y causes naive t cells to become what
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Th1 cells
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GATA-3 causes naive t cells to become what
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Th2 cells
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Th1 cells activate what
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macrophages
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bacteria and some bacteria have what effect on dendritic cells
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cause them to secrete IL-12, activates NK cells and they produce IFN-y, which activates Naive cd4 t cells to Th1 cells
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Th1 cells produce what cytokine
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IFN-y
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Inf-y expresses what IG?
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IgG3 and IgG2
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what IG is always /first produced
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IgM and IgGb (only in niave B cell)
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what is the difference between naive and memory cells
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Ig receptors
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when dendritic cells express high TGP-b and low IL-6 what happens
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activates cd4 t cells to express foxp3 and show a regulatory phono type
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when dendritic cells express both high TGP-b and IL-6 what happenes
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naive t cells become Th17 cells to increase inflammation increases number of neutorphils
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Treg cells do what
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inhibits ch4 differentiation and lysing of dendritic cells after clearing of infection
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when activated Th2 cells secret TGF-b and IL-10 what happens
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inhibits activation and growth of the cells
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activated Th1 cells secreting INF-y does what
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inhibits proliferation of Th2 cells
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gut specific homing is done by what
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expressing of a4:b7 inter grin, bind to mucosal vascular addressing MADCam -1 (only in mucosaltissue)
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how can priming of one musical tissue induce protection in other mucosal surfaces
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MAdCAM-1 in not restricted entirely to the blood vessels of intestine, also on other mucosal surfaces
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how many days does it take to activate naive b and t cells
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5 days
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what is the first responder IG
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IgM
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what causes switching of isotope (Ig)
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provided by the follicular cells (cytokines)
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wht do memory B cells do
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secrete NGF (nerve growth factors)
express Bcl-2 (inhibits cell death) expresses IgA, IgG,and IgE |
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what occurs in the innate immunity immediate pahce , how long
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0-4 hours
recognition by pre formed nonspecific and broad specific effectors, removal of infection agent |
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what occurs in the early induced innate response, how long
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4-96 hours
infection, recognition of microbial associated molecular patterns, inflammation and recruit , activation of effector cells, removal of infect |
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what occurs during the adaptive immune response, how long
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greater that 96 hours
infection, transport of antigen to lymph, recognition by naive t and b cells, clonal expansion and differentiation, removal of infection |
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what happened ar reinfection
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protective immunity: recognition by pre formed antibody and effect t cells
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what is immunological memory
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recognition by memory B and T cells, rapid expansion and activation of effector cells, agent removed
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how long is the initial immune response
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0-14 days
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what is the primary response affinity for B cell memory
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primary response - IgM. low affinity
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how long is immunological memory after reifnection
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2.5 years after a mild reinfections
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what is the secondary response for Bcell memory
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IgG, IgA, IgE much higher affinity than IgM.
secondary and subsequent responses, antibody levels produces rise |
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How can memory B cells be distinguished form naive B cells
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have under gone class switching followed by affinity maturation (naive = IgM/IgD) (positive memory IgG/ IgA)
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what is special about Memory b cells
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1) divide more rapidly
2)have lower threshold for activation 3)enhanced affinity for antigen 4) enhanced expression of MHC II |
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what are the endogenous survival factors of Mem B cells
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high levels of NGF (nerve growth factors)
high levels of NGF receptors * NGF acts as a survival signal |
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what distinguishes between naive t cells and memory t cells
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homing memory to different compartments within body (ccr7) or function (cd45)
naive t cells - have receptors for homing to 2nd lymph memoyr t cells have homing to peripheral tissues |
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memory t cells have two catagories
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Tem= effector memory cells (home to peripheral tissues, rapid response to re-cheallange infect agents
TCM- central memory t cells home to lymph initiate further T/B cell cooperation IL15 produced during viral infections, = survival signal for memory cd8 , cd4 express TLR bacterial and viral infections trigger cd4 survival |
