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��What cells are the main activators of T cells?
Dendritic cells
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Where are T cells activated?
draining lymph node, bronchial-associated mucosal tissue, peyer's patches and GALT, spleen
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How are antigens captured by dendritic cells?
TLR medieated endocytosis, macropinocytosis, cross-presentation
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Macropinocytosis
non-specific uptake of a large amount of fluid
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Cross-Presentation
capture of antigen from an infected cell by a professional APC and delivery to the MHC I pathway
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What happens after a DC uptakes an antigen?
increases efficiency of antigen capture, receptor expression that responds to chemokines, maturation of DC so they can present to T cells
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What forms of DC are in the peripheral tissue?
Immature DC- MHC is in endocytic vesicles, antigen capture occurs
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What happens when the DC is in circulation?
MHC starts to separate
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What happens to the DC in lymphoid tissue?
it becomes mature with its MHC on the surface
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How do naive t cells enter the lymph node?
HEV by homing process
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What happens to Naive cells that bind to antigen?
they are detained and slowly proliferate
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How does homing of naive T cells occur?
chemokines are secreted by stomal and DCs in the lymphnode. The T cell has a receptor that will bind to the chemokines on HEV surface.
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L-selectin on the ____ binds to _____ on the ______ resulting in _____
T-cell; glycam-1; HEV; loose binding
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T-cell binds chemokine resulting in ____
activation of LFA-1
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LFA-1 on the ____ binds _____ on the _____ resulting in ______
T cell; icam 1; HEV; tight binding
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What is the function of transient binding?
the T cell can scan for MHC-peptide complexes.
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What is co-stimulation?
Professional APC gives 2 signals to activate the naice T cell.
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What two bindings lead to co-stimulation?
TCR binding to peptide-MHC and CD28 on Tcell binding to B& on professional APC
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What happens when the t cell becomes activated?
it starts to express CTLA4 and binds to B7 more tightly resulting in reduced proliferation
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Where are dendritic cells located in the lymph node?
only in the cortical (t cell) area
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Activated DC
make B7, more MHC, chemokine, and DC-SIGN to attract and bind T cels
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Where are macrophages located in the lymph node?
cortex and follicles
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What is the role of macrophages in the lymph node?
clean up antigens/pathogens that arrive to the lymph node, process and prevent antigens, remove unwanted lymphocytes, express B7 and MHC once activated
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Where are B cells located in the lymph node?
lymphoid follicles
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what is the role of B cells in the lymph node?
antigen capture by receptor mediated endocytosis and presentation so B cell is usualy presenting peptides from antigen bound by the BCR
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Do B cells participate in naive T cell activation?
no
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What role does tyrosine kinase have in activation of t cells?
cell proliferation and development of effector functions; IL-2 is produced
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What is the process of T cell activation?
TCR binds to MHC class II. this binding triggers phosphorylation of ITAMs. Binding of CD4 to MHC II leads to ZAP-70 binding to the phosphrylated zeta chain.
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IL-2
leads to t cell differation by binding first with low affinity and then high affiniity inducing t cell proliferation
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What happens if CD28-B7 does not bind
t cell becomes anergic
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IL-12 and IFN-gamma lead to more (TH1 or TH2)
TH1
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IL-4 leads to more (TH1 or TH2)
TH2
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TGF-beta leads to more
Treg
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TH1
secretes IL-2 and Ifn-gama leading to macrophage activation
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TH2
secretes IL-4 and IL-5 leading to B cell activation and differentiation
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What is the main stimulator of CD8 cell activation?
dendritic cells
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How can CD4 help activate CD8 cells?
CE4 activates an APC cell which activates CD8 cells
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What are effector T cells
can bind to a wide range of cells that do not express B7
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What cells produce cytokines?
T cells
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What cells produce cytotoxins?
CD8 t cells
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What cascade do cytokines initiate?
receptor dimerization, JAKs and STATs which lead to transcription
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Which of the following is/are step(s) where B cell proliferation occurs?
Immediately after B cell activation AND after the large pre-B cell stage
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Is IL-2 autocrine or paracrine?
auto
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Is IFN gama autocrine or paracrine?
para
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Does CD8 bind to CD40 or FAS?
FAS
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Does CD4 bind to CD40 or FAS?
CD40
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How do CTL induce apoptosis?
they synthesize cytotoxins in inactive form when the T cell is activated in lymph node. They release the lytic granule contents when specifically bound to peptide:MHC I complex. They also secrete IFN gamma to inhibit viral replication and attract macrophages.
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How do cytotoxins kill a cell?
perforin makes holes in mambrane and granzymes initiate apoptosis
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How does FAS kill a cell?
FAS ligand binds to Fas on the target cell
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Activation of macrophage at infection site
- Causes more efficient fusion of phagosomes to lysosomes
- Release of cytotoxic molecules (free radicals, NO and proteases)
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Activation of macrophage at lymph node
- Amplify immune response
- Increased expression of MHC II and B7 positive feedback that results in more activation of macrophages at the infection site
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What two signals are required for activation by TH1?
IFN gamma and CD40 binding
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How else can macrophages be activated?
CD8 t cells produce IFN gammma plus presence of LPS
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How does TH1 control the response to intracellular macrophage pathogens?
IFN gammma and CD40 super activates the macrophage to remove the pathogen
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How does b cell activation by TH2 occur?
CD40 ligand is synthesized by the t cell, IL-4 is secreted.
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What is the end result of b cell activation
b cell proliferates and differentiates
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Cognate interaction
two different parts are recognized on the same entity
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In a conjugate vaccine, what does the BCR recognize?
polusaccharide
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In a conjugate vaccine, what epitope is displayed by MHC II?
toxoid
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What immunosuppressive cytokines do regulatory T cells produce?
IL-4, IL-10, and TGF-beta
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