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55 Cards in this Set
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IL-7
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Growth factor released by bone marrow stromal cells that is essential for B cell development
Deficiency = no B cells |
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RAG-1/RAG-2
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Recombination activation genes. Enzymes responsible for making double strand breaks in DNA for somatic recombination.
Deficiency = no T or B cells |
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Terminal deoxynucleotidyl transferase (TdT)
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Enzyme that catalyzes the addition of N nucleotides at the junctions between rearranged gene segments of the heavy chain/beta chain to create junctional diversity.
Deficiency = reduced T and B cell receptor repertoire |
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Bruton's thymidine kinase (Btk)
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Involved in transduction of survival signals from cell surface receptors during B cell development.
Deficiency = little or no circulating antibody, B cell development stops at pre-B cell stage |
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Activation-induced cytidine deaminase
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Enzyme catalyzes the recombination required for isotype switching in B cells.
Deficiency = high IgM, very little IgG or other isotypes |
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CD40 ligand
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Expressed on activated helper T cells. Binds to receptors on B cells to supply the second signal of activation and receptors on macrophages to activate them.
Deficiency = no class switching, no macrophage activation, no granuloma formation |
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Factor B
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Binds to C3b deposited on microbial surfaces. Forms part of the alternative pathway C3 convertase.
Deficiency = total lack of alternative complement activation and significantly reduced C3b deposition |
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Factor D
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Cleaves factor B into a small and large fragment to form the alternative C3 convertase
Deficiency = total lack of alternative complement activation and significantly reduced C3b deposition |
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CR1 (complement receptor 1)
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Expressed on APCs and PMNs. Binds to C3b and C4b opsonins to help neutrophils and macrophages phagocytose the pathogen.
Can also bind to C4b and C3b to make them more susceptible to inactivation by factor I. |
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CR2
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Expressed on B cells (as part of BCR) and follicular dendritic cells. Binds to C3d, C3dg, or iC3b (degradation products of C3b). For B cells, is a synergizing signal when the BCR binds to its ligand - leads to B cell activation. For dendritic cells, allows long-term retention of immune complexes for long-term stimulation of B cells.
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CR3 and CR4
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Expressed on macrophages and neutrophils. Bind to iC3b. Sufficient to activate phagocytosis.
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C1 Inhibitor (C1INH)
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Soluble complement regulatory protein. Binds to activated C1r:C1s to cause dissociation from C1q. Reverses the low level spontaneous activation of C1q.
Deficiency = HANE (hereditary angioneurotic edema) from excess anaphylatoxin production |
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C4-binding protein (C4BP)
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Soluble complement regulatory protein. Binds to C4b of the C3 convertase to displace the C2a fragment and deactivate the convertase. Makes the C4b fragment more susceptible to cleavage by factor I.
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Factor H
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Soluble complement regulatory protein. Binds to C3b to make it susceptible to cleavage by factor I.
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Factor I
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Inactivates C3b and C4b to shut down C3 convertases.
Deficiency = depletion of C3 as C3 convertase amplifies out of control. Prevents formation of iC3b ligand for CR3 to reduce opsonization of bacteria. More susceptible to pyogenic bacteria. |
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Decay-accelerating factor (DAF)
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Cell surface regulatory protein. Binds to C4b and C3b to cause dissociation from convertase and inactivation.
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Membrane co-factor protein (MCP)
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Cell surface regulatory protein. Binds to C4b and C3b to make them susceptible to cleavage by factor I.
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CD59/protectin
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Binds to the C5b,6,7,8 complex to prevent polymerization of C9 and the formation of the MAC.
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TAP transporter complex
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Loads short, degraded peptides from the proteasome onto the MHC class I molecules being synthesized in the ER.
Deficiency = no MHC class I molecules on cell surface |
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HLA-DM
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Removes CLIP from the peptide-binding groove of an MHC class II molecule once the MHC complex is in the phagolysosome.
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CD3
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Expressed on all T cells. Acts as the signal transduction unit for the T cell receptor. ITAMs initiate signaling via phosphorylation cascade.
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CD28/CTLA-4
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Found on T cells. Binds to the B7 ligand on APCs to deliver the co-stimulatory signal that is required for T cell activation.
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LFA-1
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Cell adhesion molecule expressed on lymphocytes that can bind to ICAM-1, ICAM-2, and ICAM-3 on target cells.
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CD2
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Cell adhesion molecule expressed on lymphocytes that can bind to LFA-3 on target cell.
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CD34
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Marker for hematopoietic stem cells in bone marrow.
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Differentiation into Th1 cells
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Caused by presence of IL-12 (macrophages and dendritic cells) and IFN-gamma (NK cells).
Or high concentrations of antigen that bind tightly to the TCR. Inhibited by IL-10 and TGF-beta. |
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Cytokines released by Th1 cells
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IL-2, IFN-gamma, TNF-beta -
for activation of macrophages, class switching to IgG1 and IgG3, and cell-mediated immunity. IL-3, GM-CSF - induction of macrophage differentiation in bone marrow. LT, TNF-alpha - helps macrophages exit blood vessels |
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Differentiation into Th2 cells
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Caused by presence of IL-4 and IL-6.
Or low concentrations of antigen that bind weakly to the TCR. Inhibited by IFN-gamma. |
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Cytokines released by Th2 cells
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IL-4, IL-5, IL-13, IL-10, TGF-beta - for humoral immune responses and class switching to IgA, IgE, IgG2, and IgG4.
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Tregs
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Express CD25 surface protein and transcriptional repressor FoxP3.
Differentiation caused by activation in presence of TGF-beta during thymic development. Recognize self-determinants. Produce TGF-beta and IL-10 to prevent Th0 activation. |
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Th17
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Differentiation caused by activation in presence of TGF-beta, IL-6, IL-21, IL-23.
Produce IL-17 (promote neutrophil chemotaxis) and IL-22 (cause antimicrobial production by epithelial cells). Deficiency = increased susceptibility to opportunistic pathogens. |
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Th3 cells
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Differentiation caused by activation in presence of TGF-beta, IL-4, IL-10.
Produce TGF-beta, IL-10. Involved in mucosal immunity and preventing immune reactivity to non-pathogenic, non-self antigens. |
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L-selectin
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On naive T cells and CD4+ T cells. Bind to CD34 and GlyCAM-1 molecules (mucin-like addressins) on HEV to enable the T cell to move into secondary lymphoid tissues.
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PECAM-1
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Expressed on activated effector T cells. Allows them to move between endothelial cells and enter inflammatory, infected tissues.
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LFA-1 and VLA-4
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On effector T cells. Can bind to ICAM-1 and VCAM-1 respectively on activated peripheral vascular endothelium to allow for rolling of lymphocyte as it migrates to inflammatory tissues. Will be activated by cytokines released from endothelium.
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DC-CK
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Chemoattractant expressed by mature dendritic cells that attracts naive T cells.
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LFA-1:ICAM-1 interaction
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LFA-1 expressed on T cells and ICAM-1 expressed on APCs. They bind and TCR binds to the MHC complex to sample peptide. Causes a conformation change in LFA-1 that increases affinity and prolongs cell-cell contact for better peptide sampling.
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2 signals of activation for macrophages
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1. IFN-gamma
2. CD40L binding to CD40 receptor on macrophage Both supplied by Th1 cells. |
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IFN-gamma
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Produced by CTLs and Th1.
Activates macrophages to increase MHC expression, phagocytosis. Activates NK cells. |
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LT (TNF-beta)
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Produced by Th1.
Activates macrophages, increases NO production. |
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IL-4
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Produced by Th2.
Activates B cells, increases MHC II expression, promotes switching to IgG1, IgE. Promotes growth and survival of T cells. |
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IL-5
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Produced by Th2 cells.
Causes class switching to IgA. Increases eosinophil growth and differentiation. |
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IL-10
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Produced by Th2 and Tregs.
Inhibits Th1 differentiation. Anti-inflammatory - inhibits cytokine release by macrophages. |
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IL-3
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Produced by Th1, Th2.
Growth factor for progenitor hematopoietic stem cells. |
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TNF-alpha
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Produced by Th1, some Th2, some CTL.
Activates macrophages, induces NO production. Activates microvascular endothelium. |
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GM-CSF
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Produced by Th1.
Increases production of granulocytes and macrophages and dendritic cells. |
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TGF-beta
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Produced by Tregs.
Inhibits class switching to IgA. Inhibits growth of T cells but promotes survival. Inhibits macrophage activation. |
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IL-17
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Produced by Th17 cells.
Stimulates neutrophil recruitment. Stimulates epithelial cells to secrete chemokines. |
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Fc-gamma-RI
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High affinity IgG receptor.
Causes uptake, stimulation, activation of respiratory burst, induction of killing |
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Fc-gamma-RIII
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Receptor for IgG1.
Induces ADCC killing by NK cells. |
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Fc-epsilon-RI
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High affinity receptor for IgE on mast cells and eosinophils. Can bind to Ab without antigen.
Induces degranulation when antigen binds. |
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TLR2:TLR6
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lipoteichoic acid (G+ bacteria) and zymosan (yeasts)
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TLR3
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viral dsRNA
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TLR4:TLR4
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lipopolysaccharide (G-)
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TLR7 and TLR8
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viral ssRNA
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