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90 Cards in this Set
- Front
- Back
Fever is caused by the systemic action of
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TNF-a and IL-1
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What is the main source of TNF-a and IL-1?
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macrophages
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Do activated T cells secrete any TNF-a?
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yes
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Nothing activates macrophages like _____!
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IFN-gamma
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Where is IFN-gamma produced?
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NK cells, CD4 T helper (main), CD8 T cells(minor)
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define cytokines
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polypeptides produced during immune response that mediate/regulate response
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cytokine method of action
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autocrine, paracrine, or endocrine(TNF-a and IL-1)
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Is cytokine release long/extended?
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no, it is brief, limited
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define pleiotropic
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one cytokine has multiple functions
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are cytokines pleiotropic?
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Yes
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Are cytokine redundant (multiple cytokines have similar functions)? Ex?
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Yes, Example TNF-a and IL-1
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Cytokines and feedback loops
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cytokines influence the secretion/action of other cytokines
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Where do T cells originate?
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bone marrow, mature in Thymus
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Where do B cells originate?
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Bone marrow
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Is the generation of T and B cells steady-state/random?
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yes
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Have Naïve cells yet encountered an antigen on their TCR or BCR they can bind?
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no
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What is the consequence of lymphocyes not finding an antigen to bind?
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death within a few weeks
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Which are harder to activate, naïve, effector, or memory cells?
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naïve
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What is the only location where lymphocytes are activated?
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in the peripheral lymphoid organs
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What makes dendritic cells the only cells able to active naïve t cells?
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they express enough MHC and costimulatory molecules and (IL-12) to activate a naïve T cell
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Naïve cells that bind antigen will become _____ or ______
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effector or memory cells
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what is the lifespan of effector cells?
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few days
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Generally in peripheral blood do we have more memory and effector or naïve cells?
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naïve
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B cell function
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make antibody
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T cell function
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migrate to tissues where CD4 make cytokines which activate other cells like macrophages or CD8s
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How long can memory cells be quiscent for?
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years
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how are memory cells reactivated?
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by seeing their specific antigen again.
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Are memory T cells heterologous?
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Yes (CD4+TH1, TH2, TH17; CD8+ CTL)
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Do we know much about memory B cells?
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No, most of what we know is about memory T cells
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Where are memory T cells found?
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everywhere
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Memory cells are dependent on what IL?
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IL-7
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What does IL7 do for memory cells?
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helps them survive and divide from time to time
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Are memory cells easier or harder to activate than naïve cells?
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easier
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Why is T cell reactivation easier than naïve cell activation?
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doesn’t need dendritic cells, can occur outside of the lymph nodes
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Some activated B cells (from T-dependent responses to protein antigens) differentiate into long-lived memory cells which are:
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heterologous (HC of BCR is isotype switched); found mostly in lymphoid organs; dormant unless reactivated; easier to activate than naïve cells)
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What are the 4 types of CD4 TH cells?
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TH1, TH17, TH2, Tregs
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What is the 5th type of T cell
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CD8+
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TH1
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stimulate phagocyte-mediated ingestion (opsonization) and killing of microbes
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TH17
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produce IL-17, mediate inflammation, powerful recruitment of neutrophils and monocytes
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TH2
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immunity to parasites (allergies too) mediated by eosinophils and mast cells. Alternatve macrophage activation, production of neutralizing vs opsonizing antibodies
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Tregs
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Regulatory T cells,
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CD8
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kill infected cells
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What 2 cytokines favor differentiation of naïve CD4 T cells into TH1 cells?
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IL-12 from DCs and macros, plus IFN-gamma from NK ells or TH1 cells
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What signaling pathway does IFN-y activate?
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STAT 1 signalling pathway
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STAT 1 induces expression of what?
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T-bet- don’t forget T-bet!!!
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Il-12 acivates what STAT signaling pathway
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STAT 4
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What is the one thing to remember about TH1 cells?
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They produce IFN-y
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Is IFN-y more or less potent than IFN-a and IFN-B?
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IFN-y is less potent
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IFN-y promotes__________.
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phagocytosis
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IFN-y promotes B cell isotype switch to
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IgG/IgG3 isotypes
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IgG1/IgG3 isotypes opsonize via ____ receptorson phagocytes
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Fc
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IgG1/IgG3 activate the ________ pathway and opsonize microbes via _______ on phagocytes
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Classical complement, complement receptors (CR1)
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IFN-y is a potent activator of macrophages- increases their production of
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NO, ROS, MHC2, B7 (costimulatory molecule)
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Steps to class switching of B cells in lymph node
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1- TCR binds MHC2 on B cell. 2- CD40L on T cell binds CD40 on B cell. 3- Multiple direct interactions cause secretion of IFN-y by the T cell. 4- Direct interactions and IFN-y causes B cell to class switch from IgM to IgG1 or IgG3
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B cells class switch from _______ to _________or ________ through TH1 cell binding
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IgM to IgG1 or IgG3
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Steps to activation of MACROPHAGES by TH1 cells
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1- TCRs on T cell bind to MHC2/peptide complex on macrophage 2- CD40L on T cell binds CD40 on macrophage 3- Direct interactions cause secretion of IFN-y by TH1 cell which activates macrophage.
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What does the secretion of IL-12 by macrophage do?
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amplifies the macrophage activation process
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IMPORTANT- Activated macrophages secrete what cytokines?
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TNF-a, IL-1, and IL-6
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Il-1 and TNF-a induce what?
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FEVER!!!!!!!!
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Can TH1 cells also make some TNF-a directly?
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Yes
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Do TH1 cells secrete IL-2?
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Yes
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What IL2 chain do TH1 cells EXPRESS?
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IL-2Ra chain (CD25)
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What does IL-2Ra convert?
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IL2-R from low to high affinity so they bind IL-2 better
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Which IL is a major autocrine/paracrine proliferator for T cells?
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IL-2
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IL-2 is a proliferation factor for what cells?
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T cells, NK cells, B cells, and Tregs
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IL2 and CD8 relation
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IL2 activates naïve CD8 cells
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What Interleukins to TH17 cells produce?
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IL-17 and IL-22
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What cytokines favor development of TH17?
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IL-6, IL-23 and TGF-B
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Do TH17 cells have a role against some bacterial/fungal infections?
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Yes
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What does IL-17 do?
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causes chemokine/cytokine production by various cells, strong recruitemnt of neutrophils/monocytes
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What does IL-22 do?
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maintain epithelial barrier
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Type 1 hypersensitivity
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Immediate, IgE mediated
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Type 2 hypersensitivity
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antibody mediated (not IgE) (
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Type 3 hypersensitivity
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immune complex mediated- "floated there and got stuck"
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Type 4 hypersensitivity
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cell-mediated
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Damage of Type 4 caused by:
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1- macrophages activated by IFN-y predominantly from TH1 cells (also called Delayed Type hypersensitivity). IMPORTANT 2- killing of infected cells by CD8s
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Define Hypersensitivity
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Damage caused due to an immune response
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Type 4 hypersensitvity is caused by __________
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adaptive cell-mediated immunity
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IFN-y from TH1 cells and some IFN-y from CD8 cells activate _______
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macrophages
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IL-17 from TH17 recruit_________.
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neutrophils
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Explain Delayed-Type Hypersensitivity in relation to TH1 CD4 cells
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"Some microbes have virulence factors that resist innate immune microbial killing functions of macrophage, Macrophage activation by IFN-g from TH1 cells shifts the battle in favor of the macrophage allowing it to become activated and kill the microbes. Products of activated macrophages (like ROS) are toxic to tissues, so prolonged macrophage activation injures tissues
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What types of intracellular microbes are eliminated by CD4 TH1 cells?
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phagocytosed mucrobes that survive within phagolysosomes, microbes that escape from phagolysosomes into cytoplasm. Ex: mycobacteria
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What intracellular microbes are killed by CD8 cells?
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microbes that infect nonphagocytic cells. Ex: all viruses
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Define immunologic synapse in terms of CD8 CTLs
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CTL adheres to target cell via adhesion molecules (integrins, LFA-1, ICAM-1) which forms the immunologic synapse
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What does CTL deliver into the synapse that the target cells uptake?
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granules containing perforin and granzymes, by receptor mediated endocytosis
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What do perforins (similar to C9) do?
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make "holes"
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What do granzymes do?
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go through the "holes" caused by perforins and activate caspase-3, which causes apoptosis.
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Which granzyme activates caspase-3?
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granzyme 3
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Can CTL kill after already having killed?
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Yes
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Are CTLs and NK cells similar in their mode of attack?
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Yes
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