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99 Cards in this Set
- Front
- Back
When does adaptive immunity become active after an infection?
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Days 1-5
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When is innate immunity active?
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Always - from hours 0-6
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What are the 5 phases in an adaptive immune response?
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RaeDM
-Recognition -Activation -Elimination -Decline -Memory |
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What are the 2 branches of adaptive immunity?
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-Cell-Mediated
-Humoral |
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What does cell-mediated immunity function to combat?
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Intracellular pathogens
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What is cell-mediated immunity mediated by?
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T lymphocytes
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With what 3 other cell types do T cells interact during cell mediated immunity?
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-Phagocytes
-Infected host cells -B cells |
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What are 2 ways that intracellular microbes get that way, get into cells?
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1. Phagocytosis, surviving phagolysosomes, and getting out into the cytoplasm
2. Bind receptor and getting into the nonphagocytic cell's cytoplasm |
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How can phagocytosed microbes survive within the cytoplasm of a cell?
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By surviving the phagolyososomal enzymes and either staying within vacuoles or escaping.
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3 bugs that can survive phagolysosomes:
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-Mycobacteria
-Listeria monocytogenes -Legionella pneumophila |
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What fungus can survive phagolyosomes?
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Cryptococcus neoformans
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What 2 protozoa can survive phagolysosomes?
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-Leishmania
-Trypanosoma cruzi |
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What can bind a cell surface receptor to infect a cell?
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-All viruses
-All rickettsiae -Plasmodium falciparum and Cryptosporidium parvum |
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After T cells are born in the marrow, where do they go?
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To the thymus for maturation
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After naive T cells undergo pos and neg selection in the thymus where do they go?
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To peripheral lymphoid organs for immne surveillance.
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What capability does a naive T cell have? What can't it do?
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-Capable of antigon recognition
-Not able to eliminate pathogen |
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What does antigen recognition result in in T cells?
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1. Clonal Proliferation
2. Differentiation into effector cells |
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How is T-cell immune surveillance different than for B cells?
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T cells circulate between the bloodstream and peripheral lymphoid organs; B cells just stay sequestered in lymph organs.
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What are the different peripheral lymph organs that T cells circulate to?
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-Spleen
-Lymph nodes -Mucosal sites - skin, lungs, etc |
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What tells T cells where to go?
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Homing addresses
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What are the address ligands on vascular endothelial cells that homes T cells to skin?
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-E selectin
-CCL17 |
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After being homed to the correct endothelial site and diapedesis, how do T cells home to the actual keratinocytes in skin?
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Via interaction of
T cell: CCR10 Keratinocytes: CCL27 |
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What are CCL17, CCR10, and CCL27 all examples of?
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Chemokines
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What is the homing receptor for T cells to get to the gut?
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MAdCAM-1 ( on epithelium)
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What ligands on Tcells bind to the MAdCAM-1 receptor at gut epithelium?
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-L-selectin
-alpha4/Beta7 (both bind simultaneously) |
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After binding to the proper endothelial site and diapedesis, how do gut-homing T cells bind to the proper epithelial sites?
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Via more chemokines
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What is required for Tcell activation?
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1. Recognition of an APC-associated antigen within a peripheral lymphoid organ
2. Costimulatory signal |
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What happens when T cells are activated?
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They secrete IL-2
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What is IL-2 critical for?
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Subsequent clonal proliferation.
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What are the effector functions of effector Th cells?
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-Activation of macrophages
-Activation of B cells -Activation of other cells |
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What are the effector functions of effector Tc cells?
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-Killing of infected target cells
-Macrophage activation |
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When during an immune response does antigen processing occur in APCs?
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This is going on during the innate immune response
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What molecules on Tcells are involved in antigen recognition?
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-TCR binds Ag + MHC components
-CD4 or CD8 bind MHC |
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How do T cells bind APC's with enough affinity?
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Chemokines get produced during the innate immune response that enhance integrin binding.
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Once in lymphoid tissue, do naive T cells find and bind their appropriate Ag right away?
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No; they transiently sample many different APC/peptides
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What happens when during the sampling process in a peripheral lymph node, a Tcell encounters its appropriate Ag?
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LFAI:ICAMI binding affinity increases substantially!
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When a microbe enters the body, what is the first step in activating cell-mediated immunity?
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Phagocytic cells engulf it and then travel to peripheral lymphoid tissues to act as APCs
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What activates Tcells?
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1. Ag presentation
2. Costimulatory 2nd signal |
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When activated what do Tcells secrete?
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Il-2
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What does IL-2 do?
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Causes clonal proliferation
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What is the general effector function of CD4+ T cells?
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To secrete cytokines and help
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What type of antigens are recognized by Thelper cells?
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Extracellular
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What is the general effector function of CD8+ T cells?
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To lyse cells that are infected
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What type of antigens are recognized by Tcytotoxic cells?
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Intracellular, cytoplasmic
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What needs to happen in order for a naieve T cell to be stimulated and activated?
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It has to bind two or more TCR/CD receptors simultaneously
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What are the 2 families of TCR?
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1. alpha/beta (most common)
2. Gamma/delta |
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What does the alpha/beta receptor recognize?
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Protein antigens
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What does the gamma/delta receptor recognize?
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lipids
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What are the 2 molecules that are involved in signal transduction for Tcells?
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-CD3
-weird snake thing |
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What is CTLA-4?
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A signal transduction molecule on T cells that causes negative regulation at the end of an immune response
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What are the 2 adhesion molecules on Tcells that are involved in Tcell activation?
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-LFA-1
-VLA-4 |
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What is the ligand for LFA1 and what cells express it?
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ICAM1; on APCs and Endothelial cells
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What is the ligand for VLA4 and what cells express it?
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VCAM1; only on endothelium.
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What are the signals that increase integrin affinity during Recognition?
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-TCR induced signals
-Chemokine releases during innate immune responses |
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What happens if one of the 2 necessary signals for Tcell activation is missing?
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Tcell anergy
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But the result of both signals being present leads to:
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Tcell activation and IL-2 secretion
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What is a case in which the B7 costimulatory signal would be absent?
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If an APC was resting, deficient of the molecule B7
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What takes an APC out of resting, to express B7?
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Activation by microbes or the innate immune response.
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What does APC activation refer to?
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The increase expression of B7 costimulators, and secretion of cytokines
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What is one cytokine that active APCs secrete?
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IL-12
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Where are immature, B7 devoid dendritic cells found?
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In peripheral tissues - you don't want presentation happening out there.
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Where are mature B7 positive dendritic cells found?
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In lymphoid tissue, where you do want antigen presentation to occur!
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What is necessary for macrophages to express B7?
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Expression of bacterial protein
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When would macrophages not express B7 protein?
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When they eat nonbacterial (maybe self?) protein. you don't want that to start off a reaction.
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Rather than engulfing microbes how do Bcells get hold of antigens?
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By binding to specific antigens with their surface Ig's.
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What happens once Bcells bind to microbes via surface Ig's?
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Antigen is processed and presented via Class II MHC to present along with B7 to Tcells.
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When after T-cell activation does clonal proliferation begin?
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1-2 days after activation
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What changes to allow for the start of proliferation?
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The IL-2 receptor affinity on Tcells increases
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What will produce a greater progeny of clones in response to activation; a CD4 or CD8 Tcell?
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CD8 expands 10,000X
CD4 only expands 100-1000X |
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What happens after clonal expansion during cell-mediated immunity?
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Differentiation into effector T lymphocytes and memory cells.
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What happens to these differentiated T cells?
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They migrate out from the lymphoid tissue, back to the site of infection.
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How do the Tcell clones know where to go?
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Because of a chemokine trail left by the innate immune response
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What type of response gets rid of virus infected cells?
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CTL's cause apoptosis
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What type of response gets rid of intracellular bacteria?
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TH1 cells
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What type of response gets rid of extracellular bacteria?
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B cells
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What is the main gist of how CD4+ Thelper cells work?
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They express CD40L which binds to CD40 on APCs which provides an amplification signal to maintain the immune response.
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What APCs have CD40?
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All of them; macrophages, dendritic cells, and b-lymphocytes
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What does CD40L binding CD40 on APCs result in?
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It amplifies the immune response and activates macrophages and Bcells.
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Which subset of Thelper cells gives its amplification signal to macrophages? B cells?
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Th1 - activates macrophages
Th2 - activates B cells |
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How exactly do Th1 cells activate macrophages?
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1. By binding CD40L to CD40
2. By producing IFN-y |
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How exactly do Th2 cells activate B cells?
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1. By binding CD40L to CD40
2. By producing IL-4, 5, and 10 |
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What are three results of Th1 secreted IFN-y?
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1. Stimulates IgG1/3 Ab production to bind APC Fc receptors (opsonization)
2. Activates complement 3. Stimulates B7 expression |
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What types of pathogens is the Th1 subset directed agains?
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Intracellular microbes ingested by phagocytes
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What types of pathogens is the Th2 subset directed against?
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Protozoa, helminths, parasites.
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What does IL-4 secreted by Th2 cells do?
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Causes Bcells to make IgE which will result in mast cell degranulation.
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What does Il-5 secreted by Th2 cells do?
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Activates eosinophils
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What tells Th cells whether to become Th1 or Th2 subsets in the first place?
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Signals during naieve cell activation.
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What is the signal for Tcells to become Th1? Th2?
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Th1: IL-12 secreted by APCs
Th2: Il-4 secreted by "other cellular sources". |
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What is the function of the IL-10 secreted by Th2 cells?
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It inhibits macrophage activation
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What disease takes advantage of the fact that Th2 activation can tone down Th1 activity?
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Crohn's disease
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What activates Th2 subsets that in turn deactivate macrophage activity and prevents chronic tissue damage?
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Trichuris suis (a parasite)
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What is the effector function of Tc cells?
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They cause apoptosis of virus infected cells.
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How do Tc cells cause apoptosis?
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By secreting perforins and granzymes
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What is the other fraction of Tcells that differentiate during an immune response?
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Memory cells
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What immune response resolves and aids in wound healing after an infection is successfully eradicated?
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Innate
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Do memory T cells do anything?
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No, but they retain the capability to produce cytokines and kill infected cells.
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How long does it take for an immune response to completely resolve after an infection is eradicated?
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1-2 weeks
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What type of immune response is it when APCs are activated in response to antigen exposure?
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Innate
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What happens when APCs are activated?
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Increased expression of B7
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