UMMC Micro1 Test1 1

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sullydog101
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UMMC Micro1 Test1 1
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2012-10-01 12:13:31
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UMMC Micro1 Test1 1
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  1. Dectin-1 & -2:
    Signaling PRR: C-type lectins bind β-glucan and α-mannans, respectively; control some bacterial & fungal infections
  2. NALP3
    NOD like receptor (NLR) that responds to multiple stimuli to form a multi-protein complex termed the NALP3 inflammasome which activates the IL-1β family of cytokines (powerful mediators of inflammation) (mutation causes cryopyrinopathies such as Mucle-Wells syndrome)
  3. RIG-1 like receptors (RLRs)
    RNA helicases that detect RNA derived from viruses in the cytoplasm
  4. Inducible Nitric Acid Synthase (iNOS) Rxn
    L-arginine + O2 ð L-citrulline + NO Nitric Oxide
  5. The inflammatory cytokines
    TNF-α, IL-1, IL-6
  6. IL-12
    a bridge to induce active immunity” induces naive CD4+ T cells to differentiate into TH1 cells and Activates NK cells
  7. CXCL8
    Chemotactic Factor, used to be called IL-8, induces integrin conformational change to promote strong adhesion
  8. Sepsis
    Bacterial products in the bloodstream activate macrophages in the liver & spleen to produce high levels of TNF- α
  9. Explain Neutrophil diapedesis
    Selectin and ICAM on endothelial cells bind Siayl-Lewis and LFA-1 on neutrophils
  10. Leukocyte Adherence Deficiency (LAD)
    • LAD1 a mutation in the common chain of the β2 integrin family (CD 18).
    • LAD2 a mutation in the sialyl-Lewis ligand for selectins
    • Leukocytes do not bind adhesion molecules (ICAMs / VCAMs) on endothelial cells
    • Neutrophilia
    • Patients have recurrent bacterial infections, impaired pus formation and impaired wound healing
  11. Papain and Pepsin
    • Papain cuts the antibody into two Fab fragments and one Fc fragment
    • Pepsin cuts the antibody into a F(ab’)2 fragment and the Fc fragment dissolves
  12. Cd79s and CD79b
    Also known as Ig-alpha and Ig-beta, when membrane bound Ig crosslink, signal is started—Tyrosine Phosphorylation of ITAM and activation of transcription factors NFkB, NFAT and AP-1
  13. What chromosomes are involved with Ig?
    • Lambda light chain = 22
    • Kappa light chain = 2
    • Heavy chain = 14
  14. What CD markers are involved in the B cell co-receptor complex?
    • CD19, CD21 (CR2), and CD81
    • C3d binds to the CD21 (CR2) (CR = complement receptor)
  15. X-Linked hyper-IgM syndrome
    • Defect in CD40/CD40L
    • Elevated IgM, but no other isotypes
    • No germinal centers, no tonsils
  16. Enzyme that mediates class switching
    AID
  17. What cytokine promotes the switch to IgE? IgA?
    IL-4 promotes IgE and TGF-beta promotes IgA
  18. What does Forward angle Light scatter measure? What does side scatter measure?
    • Forward angle light scatter measures size
    • Side scatter measures granularity
  19. Natural killer cells recognize bound antibody with which receptor?
    • FcyRIII, also known as CD16
    • This happens during Antibody-Dependent cell mediated cytotoxicity
  20. What is ficolin?
    Lectin protein that binds N-acetylglucosamine to start the complement pathway
  21. What do MASP1 and MASP2 bind to?
    C1r and C1s respectively
  22. Epstein-Barr virus complexes with which receptor?
    CD21 (CR2)
  23. What prevents complement mediated lysis?
    • CD35 (CR1), MCP, DAF, and Protectin (CD59)
    • Defects in these lead to paroxysmal nocturnal hemoglobinuria
  24. Explain hereditary angioedema
    Factor XII is activated (possibly due to lack of C1 inhibitor), which activates kallikrein. Bradykinin is generated which binds Bk-B2 receptor on endothelial cells leading to edema
  25. What is the accessory molecule for the TCR?
    • CD3 and zeta: Zap70 interacts with CD3 starting Signaling cascade involves protein tyrosine phosphorylation and intracellular calcium nflux resulting in activation of transcription factors
    • Protein kinase C activates NF-kappaB
    • Calcineurin activates NFAT
    • Ras Kinase activates AP-1
  26. What do NF-kB, NFAT, and AP-1 activate in T cells?
    IL-2 transcription
  27. What are the differences in binding of alphaBeta T cells and gammaDelta T cells?
    gammaDelta T cells recognize antigen directly, they do not require MHC presentation of peptide like alphaBeta T cells do, but gammaDelta T cells have a restricted repertoire
  28. What chromosome is the MHC complex found on?
    6
  29. What genes encode proteosome subunits?
    LMP 2 and LMP 7
  30. What genes encode peptide transporters from cytosol to ER?
    TAP 1 and TAP 2
  31. What do the terms double positive and double negative refer to in relation to T cells?
    • before cell rearranges it is double negative (CD3- CD4- CD8-)
    • If cell rearrange alphabeta TCRs they become double positive, CD3+ CD4+ CD8+
    • If cell rearranges gammadelta it becomes CD3+ but CD4- and CD8-
  32. Where does T cell alphabeta selection occur?
    • Positive selection in the cortex of thymus (to determine if cell becomes CD4+ or CD8+)
    • Negative selection in the medulla of thymus (removes T cells that react with self)
  33. What is Bare lymphocyte syndrome I?
    • Tap-1/2 deficiency – can’t transport antigen associated peptides to the ER to combine with MHC class I
    • CD8 T cell numbers are very low
    • Increased susceptibility to viruses
  34. What is the enzyme that catalyzes CLIP removal?
    HLA-DM
  35. What is Bare lymphocyte syndrome II?
    • MHC class II deficiency – CD4 cells cannot be positively selected in Thymus and few develop
    • Ig levels are low due to no T cell help
    • Increased susceptibility to pyogenic and opportunistic pathogens such as Pneumocystis jiroveci
  36. What do superantigens bind? What response is triggered?
    • MHC II and TCR Vbeta regions of CD 4 T cells
    • IL-1, IL-2, TNF-alpha
  37. What functions does CD28 binding to B7 have on T cells?
    • h AP-1 & NFkB, stabilizes IL-2 mRNA → increased IL-2 synthesis (100X)
    • Induces expression of CD25 (high affinity IL-2 receptor)
    • Induces proliferation
    • h Bcl-XL (anti-apoptosis) promotes cell survival
  38. What do Cyclosporin A and FK 506 (tacrolimus) do?
    inhibit IL-2 production in T cells
  39. What do Daclizumab and Basiliximab do?
    • CD 25 blocking antibodies
    • If CD25 is blocked, then IL-2 only binds with moderate affinity instead of strong affinity
  40. What does Sirolimus (rapamycin) do?
    Inhibits IL-2 signaling and proliferation of T cells
  41. What cells are Foxp3+?
    TH3, Thymic CD4 T cells, and nTreg cells
  42. What do Naïve CD4 T cells differentiate into in the presence of IFN-gamma and IL-12 and what do they produce?
    • TH1 cells that express T-bet
    • and produce IL-2, IFN-gamma, and LT
    • During viral and bacterial infections IFN-gamma is produced by NK cells and IL-12 by macrophages
  43. What do Naïve CD4 T cells differentiate into in the presence of TGF-Beta and what do they produce?
    • Treg Cells that express FoxP3, CD4+, and CD25+
    • and produce TGF-Beta and IL-10
  44. What do Naïve CD4 T cells differentiate into in the presence of TGF-Beta and IL-6 and what do they produce?
    • TH17 cells that express RORgammaT
    • and produce IL-6 and IL-17
    • TH17 cells are produced in the pro-inflammatory phase of a bacterial or fungal infection
    • IL-17 stimulates fibroblasts to produce cytokines and chemokines to attract neutrophils
    • IL-23 supports TH17 growth expansion
  45. What do Naïve CD4 T cells differentiate into in the presence of IL-4 and what do they produce?
    • TH2 cells that express GATA-3
    • and produce IL-4 and IL-5
    • These cells stimulate B cells
  46. What do Naïve CD4 T cells differentiate into in the presence of IL-10?
    • Tr1 if no TGF-Beta
    • TH3 if also stimulate with TGF-Beta
    • and they produce IL-10 and TGF-Beta
  47. What are the hematopoietic cytokines?
    SCF, IL-7, IL-3, and CSF
  48. What are the inflammatory cytokines?
    IL-1Beta, TNF-alpha, IL-6
  49. What cytokines stimulate adaptive immunity?
    IL-2, IL-4, IL-5, IL-13, IFN-gamma, LT
  50. What are the inhibitory cytokines?
    TGF-Beta, IL-10
  51. What does a defect in the common gamma chain of the IL-2 receptor result in?
    X-Linked SCID
  52. Which type I cytokine receptors share a common Beta chain?
    IL-3, IL-5, and GM-CSF
  53. Which type I cytokine receptors share a common gamma chain?
    IL-2, IL-4, IL-7, and IL-9
  54. What are the type II cytokine receptors?
    INF-alpha, IFN-Beta, IFN-gamma, IL-10, and IL-13
  55. What cytokines from the TH1 and TH2 cells are antagonistic to each other?
    • IL-10 from TH2 inhibits TH1
    • INF-gamma from TH1 inhibits TH2
  56. What do nTreg cell do?
    Suppress T cell responses by secreting IL-10 and TGF-Beta
  57. What difference in cell surface molecules do activated Effector vs resting T cells have?
    • Resting exhibits L-selectin (for lymph node targeting)
    • Active exhibits VLA-4 (alpha4Beta1 integrin) (for endothelial cell targeting on VCAM-1)
    • They both exhibit LFA-1 and CD2, but activated T cells exhibit more of both
  58. What do cytotoxic T lymphocytes secrete?
    • IFN-gamma to disrupt viral replication, increase MHC, and activate macrophages
    • LT-alpha to kill target cells by apoptosis
    • TNF-alpha
  59. What CD is for the Fas-Fas ligand system?
    CD95/CD178
  60. How do NK cells recognize IgG coated cells?
    • The FcgammaRIII (CD16) receptor
    • This is known as antibody dependent cell mediated cytotoxicity
  61. What do natural killer cells secrete?
    IFN-gamma and TNF-alpha
  62. What two cytokines inhibit TH17 cell differentiation?
    • IFN-gamma (TH1) and
    • IL-4 (TH2)
  63. How do TH1 and TH2 effector cells stimulate phagocytic activity?
    They secrete IL-3 and GM-CSF
  64. What is responsible for Type 4 hypersensitivity?
    TH1 cells
  65. What cytokine promotes eosinophils and what cell produces it?
    • IL-5
    • Produced by TH2 cells
  66. What does IL-10 inhibit?
    • MHC II expression and co-stimulation in macrophages and APC
    • Production of IL-12 by macrophages and dendritic cells
  67. What does TGF-Beta inhibit?
    • T cell proliferation and differentiation
    • Activation of macrophages
    • respiratory burst
  68. What happens if the Mycobacterium leprae response is dominated by TH1 cells?
    • High Cell Mediated Immunity
    • Normal Ig
    • Granulomas
    • Controlled infection known as Tuberculoid leprosy
    • (You want it to be dominated by TH1)
  69. What happens if the Mycobacterium Leprae response is dominate by TH2 cells?
    • Weak Cell Mediated Immunity
    • High Ig levels (Hypergammaglobulinemia)
    • High bacterial load
    • Gross tissue destruction,
    • Disseminated and Lethal disease known as Lepromatous leprosy
  70. What is the homolog to CD28 that competes for binding on activated T cells?
    • CTLA-4 (CD152)
    • It inhibits T cell proliferation and decreases IL-2
  71. What are the types of hypersensitivies?
    • Type I: Anaphylaxis - IgE
    • Type II: Cytotoxic – IgM or IgG
    • Type III: Immune Complex
    • Type IV: Delayed (T cell mediated)
  72. Atopy:
    • Increased tendency to produce immediate hypersensitivity reactions
    • Imbalance between TH2 and Treg cells
    • Higher eosinophil and IgE counts
  73. What are the leukotriene receptor agonists used to treat allergic reactions?
    Montelukast (Singulair) and Zafirlukast and pranlukast
  74. Zileuton
    Inhibits lipoxygenase to prevent allergies
  75. What type of hypersensitivity reaction is erythroblastosis fetalis?
    Type II
  76. What are two types of Type III hypersensitivities?
    • Arthus reaction and Serum sickness
    • also, SLE, rheumatoid arthritis, post-strep glomerulonephritis, and farmer’s lung
  77. What are rheumatoid factors?
    Auto antibodies against the Fc portion of IgG
  78. What binds to Integrin Alpha4:Beta7
    MAdCAM-1 (mucosal associated)
  79. What integrin hones plasma cells to mucosal tissue?
    Alpha4:Beta7 (binds to MAdCAM-1)
  80. Allergic inflammation is a shift to which TH?
    TH2 with the production of IL-4 and IL-5
  81. Explain the recognition of alloantigens, Direct vs indirect
    • Direct – host T cells recognize donor MHC + Peptide on donor cells
    • Indirect – Host phagocytoses peptides from donor cells and presents them on regular MHC
  82. What is a “white graft”?
    Hyperacute rejection – preexisting antibodies to alloantigens
  83. What is acute cellular rejection?
    • Occurs within a few days to weeks after transplantation
    • T cell mediated – direct recognition of allo-MHC
  84. What is acute humoral rejection?
    • occurs within a few weeks after transplantation
    • Due to indirect allorecognition by TH cells
    • Production of allo-Ab
    • Rejection vasculitis
    • C4d staining shows because of C4d produced during classical complement activation
  85. What is chronic rejection?
    • Months to years after transplantation
    • antibody mediated – arteriosclerosis leading to lack of blood flow
  86. Which MHC classes are particularly polymorphic?
    A and B on MHC I and DRB on MHC II
  87. What happens with a mutation in FoxP3?
    XPID or IPEX
  88. What happens if there is defect in AIRE?
    APECED (also known as APS-1)
  89. What happens if there is a mutation in Fas or Fas-L?
    ALPS
  90. Goodpasture’s Syndrome
    Ab to kidney basement membrane – Glomerulonephritis
  91. Rheumatic Fever
    Ab to group A strep; cross reacts with heart muscle
  92. Myastenia gravis
    Ab to acetylcholine receptor inhibits binding of ligand to receptor on muscle cells
  93. Graves disease
    anti TSH receptor Ab stimulates thyroid cells
  94. What do Infliximab and Adalimumab do?
    They are anti TNF-alpha mAb used to treat theumatoid arthritis and GVHD
  95. What do Azathioprine and Mycophenolate mofetil do?
    Interfere with DNA synthesis, inhibit immune responses
  96. What do the terms Omab, Ximab, Zumab, and Umab mean?
    • They are the four types of monoclonal antibodies
    • Omab = fully mouse eg Muromomab (OKT3)
    • Ximab = chimeric (variable region mouse, rest human) eg Rituzimab (CD20) and Basiliximab (CD25)
    • Zumab = Humanized (mostly human, few mouse parts) eg Daclizumab (CD25)
    • Umab = fully human eg Adalimumab (TNF-alpha)
  97. Three causes of SCID
    • defect in cytokine mediated lymphocyte maturation signaling (X-linked SCID)
    • Adenosine deaminase deficiency (lymphocytes die)
    • RAG deficiency

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