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43 Cards in this Set
- Front
- Back
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What is the "anatomy" of lymphocyte activation?
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Microbe infects host
Microbe is taken up by APC at site of infection APC enters lymph circulation and into LN Naive T and B cells enter LN from circulation |
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T/F after it has been processed and presented you HAVE TO HAVE Costimulation otherwise nothign happens
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T
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What cell goes to the lymph nodes that is carrying the MHC complexed with the peptide
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Dendritic cells
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Where does the majority of antigen presentation happen?
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in the lymph node - that's why they are swollen, lots of cells are there because lots of cell presentation going on with infection
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T/F Naive T and B cells 'live in the lymph node' or hang out there
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true
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Along with the naive T and B cells there are circulating T and B cells, why?
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because if there is an antigen in the periphery the T cell has to get to the antigen - but doesn't if the macrophage and DC cell can carry it to the lymph node then T cell doesn't have to go there
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The Basics of the Lymphnode activation goes something like this:
Infection occurs in _______ site -> DC Cells travel to ________ -> activation of LN leads to _ and _ cell differentiation -> cells to ______ site |
peripheral site, LN (lymphnode), B and T cell activation, peripheral
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B Cell receptors can signal on their own, can T cells?
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NO, T Cells need accessory molecules
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Once the receptors are activated what happens within the cell
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signal transduction to lead the cell in a response (cytokine production...movement...etc)
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What are TCR (Tcell Receptors) composed of?
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it is a heterodimer linked by a disulfide bond
- majority of TCRs composed of one alpha and one beta chain (sm. subset is a gamma and delta heterodimer) |
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There is a variable and constant region on the TCR, what are these responsible for?
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variable region: where antigen binds
constant region: (constant, all TCR have this - it is below the variable region) - notice that after the transmembrane region there is a VERY short intracellular region that cannot signal on it's own. |
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What are the accessory molecules needed to help TCR signal tranduct?
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CD3: non- covalently assoc. -
Zeta Chain: also non-covalently assoc. both have long cytoplasmic intracellular domains - expression of these is required for antigen recognition and signaling |
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Out of TCR, CD3 and Zeta chain, which one recognizes the antigen and which one does the signaling?
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TCR: recognizes antigen
Cd3 and Zeta: signal |
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what type of interactions happen when TCR is activated to help signaling?
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conformation change occurs, once antigen binds to TCR
Phosphorylation occurs = signaling |
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Besides just TCR, CD3, zeta chain are there other molecules involved in T cell activation?
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yes,
CD4/CD8: specific on CD4 and CD8 cells CD28: binds molecules on surface of APC Integrin: to help bind cells tightly |
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What are the 'kinetics' of T cell activation?
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1. Adhesion to APC or target cell
2. Signal one: Ag specific activation and signal transduction (Class I or II MHC) 3. Costimulation by B7which is found on APC |
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*What is an important Co-stimulatory molecule on a T CELL and without it cannot activate??
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CD28: Activates T cell induces proliferation (clonal expansion)
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*What is an important Co-stimulatory molecule on a APC and without it cannot activate??
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B71/B72: ligates Cd28 or CTLA4 on a T cell and sends impt signals for cell functions.
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*What is an important Co-stimulatory molecule on a T CELL and without it cannot DEactivate??
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CTLA4: negative signal, stops clonal expansion (also binds B71/B72 on APC)
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How does CTLA4 work?
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it can COMPETITIVELY INHIBIT CD28 binding to B7 (because has higher binding affinity than CD28)
- when bound to B7, will ACTIVELY BLOCK SIGNALS from the TCR and from CD28 |
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what has to happen to get anergy (when cell is TOLD to DO NOTHING) with t cell and ApC?
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TCR bound to peptide on MHC on APC, but CD28 not interacting, so no signal transudction = becomes tolerogenic = anergy (not activated).
(becuase of absence of co-stim. molecules) |
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Absence of antigen-TCR interaction results in ? (ex: if CD28 binds to B7 but TCR doesn't bind to anything or tries to bind, but it's the wrong antigen (not specific for it))
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T cell will not be stimulated
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What does Co-reception of both signals do to the T Cell? (of B7+CD28 and TCR+specific AG.)
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activation of T cell
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At the termination of the immune response, CTLA-4 replaces ______ and downregulates T cell function.
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CD28
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Are cytokines produced by the T cell necessary for enchanced response?
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YES, IL-2
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T/F will still get T cell activation without cytokines.
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true, but they are crucial for enhanced response, will just get sm. response that doesn't work effectively.
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T/F NK and T cell make IL-2
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true
NK cells in innate immune response need IL-2 for inc. proliferation |
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Once the IL-2 is made, what cells does it effect?
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T cell clonal expansion, defferentiation into effector and memory cells
- Regulatory T cell development, survival function? - NK proliferation, increased cytotoxic activity |
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A naive T cell only as the Beta and Gamma chain (which doesn't bind IL-2 effectively)...what does it need to get better affinity for IL-2? (currently expressing IL-2R) can still bind IL-2 just ineffectively...
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after T cell activation - IL-2R takes the form of alpha,beta,gamma trimer which enhances affinity by 1000 fold.
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Where does primary activation of a naive T Cell occur have it has entered the ________ from circulation?
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Lymphnode, LN and once activated leave LN
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Where do activated T cells go after they have developed? and what happens to them there?
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to the infection site and are reactivated by APC and eradicate the microbe through secretion of cytokines and chemokines
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What are the main secreted products of the CTL or CD8+ T cell? and what does this product do?
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Perforins: perforate cells
Granzymes: help kill the cell Cytokines (IFNgamma) can affect any nucleated cell and the goal is to kill the cell |
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What are the two subgroups of CD4+ T Helper Cells?
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TH1
TH2 |
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When discussing TH1 CD4 T Cells what ________ immunity is it assoc. with and why?
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CELL mediated immunity
secretes: cytokines IFN gamma, and IL-1 affects: Macrophages Goal: activation |
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When discussing TH2 CD4 T Cells what ________ mediated immunity is it assoc. with and why?
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HUMORAL immunity
secretes: IL-4,5,13 Affects B lymphocytes Goal: Proliferation, Antibody secretion |
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What drives the development Th1 cells?
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IL-12, source from macrophage
Remember: cell mediated immunity - graft rejection, cytotoxicity, delayed type hypersensitivity, T-cell mediated autoimmunity ex: MS |
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What drives the development of Th2 cells?
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IL-4 - made by B cells (selfish APCs)
humoral: allergy, ab-mediated disease, other ab mediated autoimmune, tolerance (prego woman and Lupus) |
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What determines whether it will be a Th1 or Th2 cell?
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Depending on the kind of environment the Th cell is in and the signals they are receiving (even from themselves) determines whether it will be a Th2 or Th1 cell.
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What does it meant when there is 'balance' between Th1 and Th2 cells?
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When you have a lot of Th1 you there will be a lower amount of Th2
ex: when woman are pregnant they get more Th2 so, woman who have MS (a Th1 disease) when pregnant, their Th2 goes up, their Th1 goes down and they feel great during the pregnancy "protected" from MS whereas women with Lupus have worsening of symptoms |
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What is an important Th1 cytokine?
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IFN-gamma
- increases microbial killing activity - via macrophages and neutrophils - also effects B cells - promotes development of Th1 effector cells - increases expression of MHC and antigen presentation of APC |
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What is an important Th2 cytokine?
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IL-4
- stim. production of neutralizing ab - stim produ. of IgE - suppresses activation macrophages - activates eosinophils - inhibits differentiation of Th1 cells - differentiation and expansion of Th2 cells |
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T/F Th1 and Th2 can inhibit eachother to keep them regulated.
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true, if Th1 goes up, it inhibits production of Th2
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T/F all of this 'stuff' works in concert, like a symphony all affecting eachother
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true
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