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46 Cards in this Set
- Front
- Back
What are 6 pathogen associated molecular patterns (PAMPs) that stimulate an immune reaction?
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Laugh n Dump
-LPS -Flagella -N-formyl peptides -dsRNA -Unmethylated CpG DNA -Mannose -Phosphorylcholine |
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What time of immune reaction responds to PAMPs?
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Innate recognition and inflammation
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Is the innate system totally random?
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No; there are specific Pattern recognition receptors (PRRs) for each PAMP.
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Is the innate system as specific as the adaptive?
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NO
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What is the cell-mediated immune response designed to combat?
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Intracellular microbes
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What are 2 general categories of intracellular microbes?
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-Intravesicular
-Cytoplasmic |
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What is NOT involved in cell-mediated clearance of intracellular microbes?
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Antibodies
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What branch of cell-mediated immunity engenders the response to
-Intravesicular organisms -Cytoplasmic organisms |
Intravesicular: Thelper/NK
Cytoplasmic: Tkiller/NK |
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What are NK cells actually a part of?
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Innate immunity
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During a reaction to microbes, how many times do Tcells encounter antigen?
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Twice
1. In peripheral lymphoid organs (immature are activated/prolif) 2. At the actual site of infection (clones migrate) |
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So the 2 types of effector T cells in cell-mediated immunity are:
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1. CD4+ Thelper cells
2. CD8+ Tkiller cells |
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What do Thelper cells recognize?
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Antigen on MHCII
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What are the 2 subcategories of Th cells?
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1. TH1 - against intracellular microbes
2. Th2 - against parasites and allergens |
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How do Th1 cells act in general?
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By activating or ramping up inflammation - they activate macrophages and cause Ab to secrete IgG
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How do Th2 cells act in general?
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By causing plasma cells to secrete IgE, and activating Eosinophils which aid in mast cell degranulation.
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What are the effector cells that stem from Tc cells?
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CTL's - cytotoxic T cells
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What are the 2 ways in which CTLs are activated?
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1. Directly by Ag + APC
2. Indirectly by Ag + Th1 cell |
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When mature Tcell clones recognize Ag at peripheral sites of infection, how is the recognition different from the first time in lymphoid organs?
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It doesn't require a 2nd costimulatory signal.
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When Thelper cells differentiate into effector cells in peripheral lymphoid organs, what determines whether they'll become Th1 or Th2 cells?
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The cytokine environment in which they are immersed.
IL-12 --> Th1 IL-4 --> Th2 |
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How do effector T cells know where to migrate to from peripheral lymphoid organs?
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By the expression of specific integrins and CAM's on the endothelium near the inflammatory site.
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What two molecules activate endothelial cells and elevate chemokine production during innate immunity?
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-TNF
-IL-1 |
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When chemokines bind to endothelial surface proteoglycans, how does it alter the endothelial surface at the infection site?
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-Lose L-selectin so lymphocytes don't track back to lymph tissue
-Gain E-selectin and P-selectin |
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What integrins are on the lymphocyte surfaces, and what happens to them during differentiation?
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LFA-1
VLA-4 Affinity increases for tighter adhesion to the endothelium. |
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What does Effector Tcell recruitment and migration mimic?
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The inflammatory response - chemotaxis and diapedesis.
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When the Tcells migrate from the peripheral lymphoid organs to the site of infection, is it ONLY the mature clones?
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NO - it's independent of Ag-recognition; NONSELECTIVE migration.
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Why is Tcell migration nonselective?
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To maximize the effectiveness of the cell-mediated immune response so ANY antigens will be recognized at the infection site.
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What happens to the SPECIFIC clonal Tcells that do recognize antigen at the site?
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VLA expression and affinity increases to enhance adherence to the matrix.
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Where are L-selectin ligands?
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On high endothelial venules in lymph nodes.
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What are the molecules on endothelial cells at peripheral tissue sites that allow adherence to lymphocytes?
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-E-selectin ligand
-P-selectin ligand -ICAM1 (receptor for LFA-1) -VCAM1 (receptor for VLA-4) |
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Are ICAM-1 and VCAM-1 only on endothelial cells?
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No; they're also on APC's
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What would be a more effective antibody to prevent leukocyte trafficking; TS1, to block P-selectin, or Efalizumab / Raptiva which blocks LFA1/ICAM1 binding?
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LFA1-ICAM1 blocker - so Tcells can't have antigen presented to them.
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What is Alicaforsen?
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A drug that blocks transcription of ICAM-1, so endothelial cells and APCs can't bind the LFA-1 on Tcells.
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Does all endothelium express ICAM1 or VCAM1?
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No; only activated endothelium
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What activates Endothelium?
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IL1 and TNF
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What cells express L-selectin?
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Naieve Tcells
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What is the ligand for L-selectin?
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L-selectin ligand
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What is the function of L-selectin binding to L-selectin ligand?
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Adhesion of naieve Tcells to high endothelial venules in lymph nodes.
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What cells have E and Pselectin?
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Activated endothelium.
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What is the ligand for E or P selectin?
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E or P selectin ligand
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What cells have E/P selectin ligand?
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Activated effector and memory Tcells.
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What is the function of E/P selectin ligands binding E/P-selectins?
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Initial weak adhesion of the cells to activated endothelium at periphal sites of infection.
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What is this weak interaction called?
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Rolling
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What cells have LFA-1 or VLA-4?
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Activated effector and memory Tcells
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What is the ligand to LFA-1 or VLA-4 and what cells have them?
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LFA-1: ICAM1
VLA-4: VCAM1 -on endothelial cells |
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What is the function of LFA-1 or VLA-4 binding ICAM1 or VCAM1?
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Stable arrest of activated Tcells to the endothelium so diapedesis can occur at specific tissue injury sites.
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Once the effector Tcells diapedese into the tissues, what happens?
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-If the antigen is there, the TCR will bind and recognize it
-If not there, the Tcells return to circulation. |