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145 Cards in this Set
- Front
- Back
Nitric Oxide
|
-Released during phagocytosis.
-Innate immunity. -Induce phagocyte recruitment, activation, and microbial killing. -Type 1 hypersensitivity: SMC relaxation, increased vascular permeability and dilation. |
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NK cell functions
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-Secrete perforin and granzymes.
-Induce apoptosis via Fas-FasL. -Principle mediators of ADCC by recognizing IgG on infected cells (have Fc-gamma-RIII). -Release IFN-gamma to stimulate adaptive immunity. -Kill cells lacking MHC1. |
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NK cell activation
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IFN-alpha
IFN-beta IL-12 |
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NKT cells
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-Lipid-CD1 restricted.
-CD3+ and CD8- -Induce cytolysis. -Express classical T-cell receptors (alpha/beta). |
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Selectin
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-Bind carbohydrates.
-Mediate weak binding and rolling of WBC's on endothelium. -Naive T-cells express L-selectin, which binds the ligand on the HEV. -Mature T-cells lose E-selectin (to inhibit trafficking back to lymphoid tissue) and express ligand for E- and P-selectins, which are on endothelium. -P-selectin is also on platelets. |
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Integrin
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-alpha and beta subunits
-Mediate strong adhesion of WBC's to endothelium. -Integrin on WBC surface, integrin ligand on endothelium. -Switch from low- to high-affinity state via chemokines. -Also called LFA. -Bind CAM's & ECM. |
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TNF
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-Involved in innate immunity.
-Mainly from macrophage, signaled by TLR. -Also from T, NK, and mast cells. -High level indicates autoimmune disease or bacterial infection (gram negative). -Binds TNFR1 & 2, activates TRAF, induce transcription via NF-kappa-B. -Systemic effects of severe infections. -See 'biological effects' card. |
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IL-1
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-Involved in innate immunity.
-From macrophage, signaled by TLR. -Also from endothelial cells. -See 'biological effects' card. |
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PECAM-1
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-Platelet Endothelial Cell Adhesion Molecule
-On WBC and endothelium. -Induces stable adhesion and migration of WBC into tissue. |
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TLR/PRR
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-Toll-Like Receptor/Patter Recognition Receptor
-WBC's: surface & interior. -Recognize PAMPS & target phagocytosis. -Encoded in germline, so no somatic gene recombination, so limited adaptability. |
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PAMP's
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-On microbes, not host cells.
-Bacterial lipopolysaccharide, flagella proteins, mannose, dsRNA, CpG DNA. |
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Genes activated by TLR's
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-Cytokines: TNF, IL-1, IL-12.
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IL-12
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-Involved in innate immunity.
-From macrophages, signaled by TLR. Also from DC's. -Effect on NK and T-cells: activation, IFN-gamma release, increased cytotoxicity. -Induces Th1 differentiation. |
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IFN-alpha
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-From DC's and macrophages.
-Activate NK cells (antiviral). -Type 1 IFN. -Increase MCH1 expression in all cells. |
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IFN-beta
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-From fibroblasts.
-Activate NK cells (antiviral) -Type 1 IFN. -Increase MCH1 expression in all cells. |
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IFN-gamma
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-From NK cells and T-cells.
-Involved in innate and adaptive immunity. -High level indicates viral infection. -Induces macrophage activation. -Stimulates some antibody responses. -Induces expression of LMP's and MECL (replacement beta subunits of proteasome). |
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IL-2
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-Involved in adaptive immunity.
-From active T-cells (CD4 & CD8). -Self-stimulatory, induces T-cell proliferation. |
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IL-4
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-Involved in adaptive immunity.
-From Th2 cells. -Induces differentiation of active T-cell to Th2 cell. -Enhances B-cell antibody production. -Inhibits macrophage activation. |
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IL-5
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-Involved in adaptive immunity.
-From Th2 cells. -Causes eosinophil activation (to hypodense phenotype) & production in marrow. -Enhances B-cell antibody production. |
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Corticosteroids
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-Inhibit innate immunity cytokines.
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Remicade
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-Humanized antibody to TNF.
|
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Enbrel
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-Inhibits TNF action.
-Fusion of soluble TNFR with human IgG. |
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Biological effects of TNF
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-Endothelium: activation(express more selectins, integrin ligands, and chemokines), inflammation, coagulation.
-Neutrophil activation. -Hypothalamus: fever. -Liver: acute phase protein synthesis. -Muscle & fat catabolism -Apoptosis of many cell types. |
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Biological effects of IL-1.
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-Endothelium: activation (express more selectins, integrin ligands, and chemokines), inflammation, coagulation.
-Hypothalamus: fever. -Liver: acute phase protein synthesis. -T-cells: Th17 differentiation. |
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Chemokines
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-From macrophages, DC's, endothelial cells, T-cells, fibroblasts, and platelets.
-Effects on WBC's: activation, chemotaxis, increased integrin affinity. |
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IL-10
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-From macrophages, DC's, and Th2 cells.
-Effects on macrophages and DC's: inhibit IL-12 production, reduce expression of costimulators and MHC2 (inhibits macrophage activation). |
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IL-6
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-From macrophages, endothelial cells, and T-cells.
-Effect on liver: acute phase protein synthesis. -Effect on B-cells: proliferation of Ab-producing cells. -Effect on T-cells: Th17 differentiation. |
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TGF-beta
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-From many cell types.
-Inhibition of inflammation. -Induces differentiation of Th17 and regulatory T-cells. -In mucosa, induces class switching to make IgA in MALT. |
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Chemokine receptors
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-G-protein coupled 7-transmembrane receptor family.
-Important in devo, vascularization, cancer metastasis, and HIV. -Drugs: receptor antagonists to block HIV entry and mobilize stem cells during transplant. |
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Eicosanoids
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-Innate immunity.
-From phagocytes. -Induce phagocyte recruitment, activation, and microbe killing. |
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ROI's
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-Innate immunity.
-From phagocytes. -Induce phagocyte recruitment, activation, and microbe killing. |
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Defensin
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-Innate immunity.
-From phagocytes. -Small cationic peptides capable of lysing microbes. |
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Acute Phase Proteins
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-Innate immunity.
-C-reactive protein & serum amyloid A. -Produced in liver via IL-6. -Bind microbes to enhance phagocytosis. -Induce phagocyte recruitment and activation. -Circulating levels increase much during infection. |
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Lactoferrin
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-Innate immune component.
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Lysozyme
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-Innate immune component.
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2nd signals for B- and T-cell activation
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-Provided by innate immune response.
-Examples: costimulator molecules, cytokines like IL-12, complement proteins. |
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B7
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-2nd signal for T-cell activation.
-Provided by innate immune system (on APC surface). -Recognized by CD28 receptor on T-cell. -Expressed by macrophage after phagocytosis. |
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CD28
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-Receptor on T-cell for the B7 ligand.
-2nd signal for T-cell activation. |
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CR2
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-Type 2 complement receptor that recognizes Cd3 on microbe.
-On B-cell surface. -Integral membrane protein. -Part of 2nd signal (along with ITAM) for B-cell activation. |
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Proteasome proteases
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-In the proteasome's beta subunits.
-Trypsin-like: cleaves to the right of basic amino acids. -Caspase-like: cleaves to the right of acidic amino acids. -Chymotrypsin-like: cleaves to the right of hydrophobic amino acids. |
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LMP & MECL
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-Expression is induced by IFN-gamma.
-Replacements for beta subunits of proteasome. -Encoded in MHC gene. -Turns the proteasome into the "immunoproteasome." |
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TAP
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-Transporter associated with Antigen Processing.
-Transports peptides (ending in hydrophobic amino acids and of size 6-15 amino acids) into ER. -Encoded in MHC gene. -Integral membrane protein on ER. |
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Tapasin
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-Located in ER.
-Tethers newly-synthesized MCH1 to TAP so that incoming peptides can bind. |
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beta-2-m
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-beta-2-microglobulin
-Light chain of MHC1, with Ig domain. -Once it associates with MHC1 heavy chain in ER, the molecule is stable. -Does not span membrane. -Non-polymorphic. |
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MHC1 structure
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-1 heavy chain + beta-2-m
-heavy chain domains: alpha-1, -2, & -3. Alpha-1 & -2 form peptide-binding groove, and there are polymorphisms on both domains. |
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MHC2 structure
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-2 heavy chains (alpha and beta).
-Heavy chain domains: alpha-1 & -2. Beta-1 & -2. -peptide-binding groove is made by alpha-1 and beta-1 domains. -Can hold longer peptide antigens than MHC1. -Polymorphic residues on beta chain. |
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Cathepsin
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-Protease in lysosome, present in mM amounts.
|
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Ii
|
-Invariant chain.
-3 functions: scaffold & stabilizer for MHC2, barrier to peptides in ER, zip code for MHC2 transport to lysosome. -Prevents peptides in the ER that are destined for MCH1 from binding to MHC2. -Integral membrane protein in ER, becomes CLIP in lysosome. |
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CLIP
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-Class 2 Invariant chain Peptide
-Short peptide fragment derived from Ii, located in MHC2 groove while in lysosome. -Kicked out of MHC2 by HLA-DM. |
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HLA-DM
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-In lysosome, catalyzes the exchange of CLIP for antigen in MCH2 groove.
-Resembles MCH2 but lacks a peptide-binding groove. |
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CD1
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-An antigen presentation molecule (on APC's) similar to MHC.
-1 heavy chain + beta-2-m. -Present lipid antigen to NKT cells. -Not encoded in MHC gene, not very polymorphic. -Travels with Ii like MHC2. -Unclear mechanism of attaining lipid antigen. |
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MHC genetic locus
|
-Chromosome 6, 200 genes
-MHC1: 3 classical gene products, HLA-A, -B, & -C (heavy chains). -MCH2: 6 classical gene products, heterodimers HLA-DR, -DQ, & -DP (alpha and beta chains). -Polymorphic. -Codominant. -Polygenic. |
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Ankylosing Spondylitis
|
-Inflammatory disease of vertebral joints.
-93% of patients have HLA-B27. -Activating agent is a bacterium. |
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BCR
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-Membrane-bound antibody (IgD or IgM) + 2 additional membrane-bound Ig domains (Ig-alpha and Ig-beta).
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CD3
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-Associated with the TCR on all T-cells (marker).
-No ligand. |
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IgG
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-Subtypes: 1, 2, 3, 4
-Secreted because of 'tail piece' -Opsonization, complement activation, ADCC, neonatal immunity, feedback inhibition of B-cells. -Most commonly found Ig after secondary response. |
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IgM
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-Initiate B-cell response.
-Membrane-bound monomer, secreted pentamer. -Naive B-cell antigen receptor, complement activation. -Predominant Ig early in immune response. |
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CDR
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-Complimentary Determining Region.
-3 hypervariable regions in the variable part of Ig heavy and light chains and TCR. -CDR3 is the most variable, located at the junction of V and C regions. Contributes most to antigen binding. |
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TCR
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-1 alpha chain + 1 beta chain, each with Ig domains.
-Each chain has V and C regions. -Do not undergo glass switching or affinity maturation. -Do not mediate effector functions, just recognize MHC + peptide. -Coreceptors for TCR are CD4 & CD8. |
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IgA
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-Subtypes: 1 & 2
-Secreted as a dimer after binding Poly-Ig receptor at basolateral side of epithelial cell. -Mucosal immunity, neonatal passive immunity (mother's milk is IgA-rich). -Produced in MALT, 60-70% of total daily Ig production. -Made in MALT b/c TGF-beta induces class-switching. -Neutralizes pathogen in lumen. |
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IgD
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-Not secreted.
-Naive B-cell antigen receptor. |
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IgE
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-Intermediate hypersensitivity, allergies.
-Bind surfaces of mast and basophilic cells. |
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Ig isotypes
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-Differ in heavy chain.
|
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Ig allotypes
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-Differ in polymorphic domain of the constant part of heavy chain.
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Ig idiotypes
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-Differ in polymorphic domain of V region of heavy and light chains.
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Positive Selection of T-cells
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-Immature T-cells with receptors reactive to self-MHC + peptide are selected to live and proceed to next step.
-Occurs in thymus cortex. |
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Negative Selection of T-cells
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-Immature T-cells with high affinity receptors for self peptides are removed.
-Occurs in cortical-medullary junction of thymus. |
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E-selectin
|
-On endothelium.
-Bound by skin-homing lymphocytes. |
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MAdCAM
|
-Mucosal-Addressing Cell Adhesion Molecule.
-On endothelium. -Bound by gut-homing lymphocytes. |
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CAM/ICAM
|
-Cell Adhesion Molecule.
-On endothelial cell. -Binds integrin on WBC |
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Dendritic Cell Costimulatory Molecules
|
-B7-1 & B7-2
-Expressed by mature DC after differentiation of immature DC. -Costimulatory molecule for T-cells. |
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IL-2R
|
-T-cell receptor for IL-2.
-On CD4+ and CD8+ cells. -Resting T-cell has beta and gamma chains (no alpha). Low affinity state. -The alpha chain is expressed upon recognition of antigen by T-cell. This high affinity state induces T-cell proliferation. |
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Th1 cells
|
-CD4+
-Recognize MHC2. -Activates macrophages to kill intracellular bacteria by producing IFN-gamma. -Stimulate antibody production to bind APC Fc receptors. -Activate complement production. -Stimulates costimulatory molecule expression. |
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CD40
|
-Expressed on APC (including B-cell).
-Binds CD40 ligand of CD4+ T-cells. -Amplification signal to maintain immune response (i.e. not an activation signal-- signals 1 and 2 have already occurred). |
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Th2 cells
|
-CD4+
-Recognize MCH2. -Activate B-cells to become plasma cells and secrete antibody. -Release cytokines that inhibit macrophage activation. -Produce IL-4, -5, & -10. -Involved with allergies and parasites, eosinophilic inflammation. |
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CTL
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-CD8+ T-cell, cytotoxic.
-Recognizes MCH1. -Activated directly (antigen + presenting cell) or indirectly (antigen + Th1 help). -Secretes perforin & granzyme. -Expresses Fas Ligand to induce apoptosis of target cells, which have Fas Receptor. |
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Fas
|
-Fas Ligand on CTL's binds the Fas Receptor on target cell to induce apoptosis.
-"Death Receptor" |
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Proteoglycans
|
-Located on endothelial surface.
-Bind chemokines. |
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CCR7
|
-Cell marker on mature DC's and other cells, targeting them for migration back into lymphoid tissue for presentation to T-cells.
|
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TS1
|
-PSGL1-Ig: Humanized recombinant antibody to human PSGL-1 glycoprotein (ligand for P-selectin).
-Drug to prevent WBC's from adhering to endothelium and causing inappropriate inflammation & thrombosis. |
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Raptiva
|
-Humanized monoclonal antibody that blocks LFA-1 interactions with ICAM-1 on APC.
-Drug for severe plaque psoriasis. -Blocks T-cell activation and binding/trafficking into the dermis. |
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Alicaforsen
|
-Drug for ulcerative colitis.
-Antisense oligonucleotide that blocks ICAM-1 transcription to inhibit binding and migration of WBC's into tissue. |
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SCID
|
-50% cases: X-linked defect in common gamma chain of the IL-2 receptor.
-Lack T- & NK cells; B-cells non-functional. -Opportunistic infections, diarrhea, failure to thrive. -100% mortality without BMT. -Diagnosis: CBC, lymphopenia, lymphocyte enumeration (will have low naive T-cell levels). |
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Toxic Shock Syndrome
|
-Bacterial superantigens (TSST-1) cause excessive stimulation of T-cells and macrophages.
-Massive & unregulated cytokine production (IL-1, TNF-alpha, IL-2, IFN-gamma). -Poor antibody response to TSST-1. |
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Acute Infectious Mononucleosis
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-CTL mediate killing of EBV-infected B-cells.
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ITAM
|
-activating motif on Ig-alpha and Ig-beta chains of BCR
-Become phosphorylated to activate transcription factors. -2nd signal for B-cell activation, along with CR2 (1st is antigen recognition). |
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ITIM
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-inhibitory motive on Fc receptor on B-cell surface.
-Phosphorylates things to shut down ITAM's function. -Fc receptor is upregulated upon B-cell activation= negative feedback. |
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CD5
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-Cell marker on B-1 B-cells.
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B-1 B-cell
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-Has CD5 cell marker & IgM on surface.
-Present in mucosal tissues & peritoneal cavity. -Recognize polysaccharides, lipids, etc. (T-cell independent). -Become short-lived plasma cells that secrete mainly IgM. |
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Marginal zone B-cell
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-Located in spleen & other lymphoid organs.
-Recognize polysaccharides, lipids, etc. (T-cell independent). -Become short-lived plasma cells that secrete mainly IgM. |
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Follicular B-cell
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-Located in spleen & other lymphoid organs.
-Recognize protein antigen (T-cell dependent). -Become long-lived plasma cells that secrete IgG, IgA, and IgE (isotype-swiching, affinity maturation occur). |
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ADCC
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-Antibody-Dependent Cellular Cytotoxicity.
-IgG coats host cells displaying antigen, then NK cells bind at Fc region and crosslink Fc-gamma-RIII's to kill the cell. -IgE coats parasites, eosinophil binds at Fc region with Fc-epsilon-RI and kills parasite. |
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C1
|
-Initiates classical complement pathway.
-Binds 2 Fc regions of IgG or IgM (crosslinking) that is bound to specific antigen on microbe surface. -Stabilized by crosslinking and activated for enzymatic cleavage of C4 & C2. |
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C3
|
-Initiates alternative complement pathway.
-Spontaneously or enzymatically cleaved by hydrolysis into C3a and C3b. -Present in very high concentration (mg amounts). |
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C3b
|
-Cleavage product of C3.
-Covalently binds microbe surface (non-specific), becomes stable. -Acts as an opsonin and as a component of C3 & C5 convertases. -A substrate for Factor B, then binds Bb. |
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C3a
|
-Cleavage product of C3.
-Stimulates inflammation, activates macrophages. |
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C3 convertase
|
-Alternative: C3b + Bb
-Classical: C4b + 2b -Cleaves C3 in addition to spontaneous hydrolysis. |
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C5 convertase
|
-Alternative: C3b + Bb + C3b
-Classical: C4b + 2b + C3b |
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C4
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-Classical complement pathway.
-Cleaved by C1 into C4b & C4a. |
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C4a
|
-Cleavage product of C4.
-Stimulates inflammation. |
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C4b
|
-Cleavage product of C4.
-Covalently binds microbe where IgG is present and C1 is bound. -Binds C2 for cleavage by C1. |
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C2
|
-Classical complement pathway.
-Cleaved by C1 after binding C4b. -Cleavage product acts as the enzyme component of C3 & C5 convertases. |
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Factor B
|
-Alternative complement pathway.
-Cleaved by C3b. -Cleavage product Bb acts as the enzyme component of C3 & C5 convertases. |
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MBL
|
-Mannose-Binding Lectin.
-Lectin complement pathway. -Binds & crosslinds mannose on microbe surface (similar structure to C1), then activates the classical pathway just like C1. |
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C5
|
-Cleaved by C5 convertase into C5a & C5b.
-C5a induces inflammation by binding macrophages. -C5b initiates MAC formation. |
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MAC formation
|
-Membrane Attack Complex.
1. C6 binds C5b. 2. C7 binds C5b & C6, inserts into microbe membrane. 3. C8 binds C5b, C6, & C7. 4. C9 binds C5b, C6, C7, & C8. 5. C9 polymerizes to Poly-9 ring pore. |
|
C1 Inhibitor (C1 INH)
|
-Inhibits C1 serine protease activity.
-Inhibits classical complement cascade. |
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Factor I
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-Proteolytically cleaves C3b and C4b.
-Inhibits classical and alternative complement cascades. |
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Factor H
|
-Causes dissociation of (alternative pathway) C3 convertase subunits.
-Cofactor for Factor I. -Inhibits alternative complement pathway. |
|
DAF
|
-Decay Accelerating Factor.
-Located on blood cells and endo/epithelial cells. -Causes dissociation of C3 convertase subunits. -Inhibits alternative and classical complement cascades. |
|
C2 or C4 Deficiency
|
-Minimal disease, often asymptomatic, but most common.
-Autosomal recessive, deletions. -Increased autoimmune-like disorders (lupus-like). -Suggests classical complement pathway is not essential. -Recurrent bacteremia. |
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C9 or MAC Deficiency
|
-Increased susceptibility to Neisseria infection.
|
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C3 Deficiency
|
-Increased susceptibility to infections.
-Fatal in early life. |
|
C1 INH Deficiency
|
-Causes hereditary angioneurotic edema.
-Excessive complement activation leads to edema in larynx and other tissues. |
|
Poly-Ig Receptor
|
-Binds J chain of IgM or IgA.
-Located on basolateral side of epithelial cell. -Secreted as a complex with the Ig into lumen. |
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FcRn
|
-Neonatal FcR.
-Located on epithelial cell surface to transport maternal IgG's to the neonate. -Also expressed by placenta to uptake IgG. |
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Conjugate Vaccine
|
-Microbial polysaccharide + protein.
-Stimulates both humoral & cell-mediated immunity. |
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Infections with impaired cellular immunity
|
-Opportunistic infections (fungi, viruses, bacteria, protozoa).
|
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Infections with impaired antibody production
|
-Encapsulated bacteria, M. pneumonia, giardiasis.
|
|
Infections with impaired complement system
|
-Encapsulated bacteria, recurrent meningococcal infections
|
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XLA
|
-X-linked Agammaglobulinemia.
-80% of all agammaglobulinemias. -Resp. tract infections with encapsulated bacteria, otitis. -Low IgG AND low IgA or IgM, B-cells are extremely low (<1%), but normal T-cell # and function. -Mutation in Btk. -Treat with IV or sc gammaglobulin. |
|
CVID
|
-Common Variable Immunodeficiency.
-Defect in B-cells. -Resp. tract infections with encapsulated bacteria, bronchiectasis, GI infections, autoimmunity. -Diagnosis: Low IgG low IgA OR IgM (decrease in 2 of 3 major isotypes), poor response to vaccines. -Treatment: Ig replacement. |
|
DiGeorge Syndrome
|
-Defect in pharyngeal pouches 1-6 (including thymus).
-Low T-cell and antibody count. -Microdeletion in chromosome 22, Tbx1 gene. -Abnormal facies, lymphpenia, thrush, recurrent sinopulmonary infections, cleft palate, cardiac abnormaliities, hypocalcemia. -Diagnosis: FISH & microarray chip. |
|
CGD
|
-Defect in NADPH oxidase of phagocytes.
-Causes: X-linked (76%) or autosomal recessive. -Recurrent abcesses, lymphadenitits, esophageal stricture by granuloma. -Diagnosis: DHR test. -Treatment: antibiotics, IFN-gamma, BMT. |
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Common gamma chain
|
-Shared component of many IL receptors (IL-2, -4, -7, -15, -21)
|
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TREC's
|
-T-cell Receptor Excision Circles.
-Circular pieces of DNA generated with T-cell maturation, from VDJ joining. -Surrogate marker for # of normal naive T-cells. -Screening for SCID: low TREC's. |
|
Agammaglobulinemia
|
-Pre-BCR checkpoint defects.
-Decrease in all Ig subtypes, low # B-cells. -Many causes: autosomal recessive or X-linked. -Same clinical phenotype. |
|
Btk
|
-Kinase that phosphorylates PLC-gamma-2, works with BLNK.
-Mutation=no Btk protein=XLA |
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Hypogammaglobulinemia
|
-Ig isotype defects.
|
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C5-9 Deficiency
|
-Recurrent meningococcal infection.
-No association with autoimmune disease. -Autosomal recessive. |
|
MyD88 & IRAK-4 Mutations
|
-Pyogenic bacterial infections & defects in TLR signaling (TLR depends on these kinases).
-Diagnosis: standard immune screens are normal and not helpful. Decreased inflammatory cytokine production in vitro in response to IL-1 & TLR agonist. |
|
Type 1 hypersensitivity
|
-IgE-mediated "immediate type"
-IgE coats antigen, activates mast cells & basophils, other inflammatory cells recruited. -Early (histamine) and late (eosinophils: leukotrienes, prostaglandins, kinins) stages. -No complement involved. -Allergies (rhinitis, nasal and ocular pruritis), asthma, anaphylaxis, urticaria. |
|
Type 2 hypersensitivity
|
-ADCC (cytotoxic type).
-Nonsoluble antigen, tumor cells. -Autoimmune hemolytic anemia, erythroblastosis fetalis, Goodpasture syndrome, drugs bound to RBC & platelets (penicillin), myasthenia gravis, Grave's disease, rheumatic fever, blisters. -IgG & IgM bind antigen, phagocytosis or lysis (by C8/9 or NK cell) of cell. |
|
Type 3 hypersensitivity
|
-Immune complex mediated.
-Soluble antigen. -Arthus rxn, serum sickness, SLE, acute glomerulonephritis, Farmer's lung. -Antigen/IgG complexes deposit in low flow sites, activate complement, attract PMN's, release lysosomal enzymes. |
|
Type 4 hypersensitivity
|
-Delayed type cell-mediated (no Ig involvement).
-Antigen enters skin, binds self protein, complex is phagocytosed, T-cell response (Th1 & CD8)- cytokines or cytotoxicity. -Antigen is soluble (Th1) or cell-associated (CD8). -Contact/Rhus dermatitis, TB, transplant rejection. |
|
H1 & H2
|
-Histamine receptors, type 1 hypersensitivity.
-H1: SMC contraction, increased vascular permeability. -H2: increased vascular permeability, stomach acid release. -Both: vasodilation, pruritis. |
|
Tryptase
|
-Type 1 hypersensitivity.
-Released from mast cell in early phase. -alpha-tryptase: constitutively released. -beta-tryptase: only released with mast cell activation. -Induces remodeling of connective tissue matrix. |
|
Mast cell products
|
-Early phase (stored in granules): enzymes- tryptase, chymase, cathepsin G, and carboxypeptidase.
-Late phase (synthesized): cytokines- IL-3, -4, -5, & -13, GM-CSF, and TNF. Also chemokines- MIP-1-alpha, RANTES, Eotaxin. Also lipid mediators- leukotrienes C4, D4, & E4, and PAF. |
|
MIP-1-alpha
|
-Released by mast cell.
-Late phase of Type 1 hypersensitivity. -Chemokine for monocytes, macrophages, PMN's, T-cells, eosinophils. |
|
RANTES & Eotaxin
|
-Released by mast cell.
-Late phase of Type 1 hypersensitivity. -Chemokine for T-cells and eosinophils (eosinophils have the only receptor for eotaxin). |
|
Leukotrienes C4, D4, and E4
|
-Lipid mediators released by mast cells in late phase Type 1 hypersensitivity.
-Eosinophil migration, SMC contraction, vascular permeability & dilation, mucus hypersecretion. |
|
PAF
|
-Platelet Activating Factor
-Lipid mediator released by mast cells in late phase Type 1 hypersensitivity. -Attracts eosinophils & other WBC's, activates eosinophils, PMN's, and platelets, increases production of lipid mediators. |
|
Conditions of elevated eosinophil count
|
Mnemonic: NAACP.
-Neoplasia -Asthma -Allergy (atopic disease & drug allergy). -Connective tissue disease. -Parasitic disease. |
|
Steroid treatment of Type 1 hypersensitivity
|
-Rapid eosinophil apoptosis.
-Inhibit IL-5 production, leading to decreased eosinophil release from marrow and more apoptosis. -Steroid binds GR-alpha, inhibiting AP-1 and NF-kappa-B. |
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Products of eosinophils
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-Released from crystalloid granules with core MBP.
-Lysophospholipase, major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), PAF, LTC4 (leukotriene). |