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103 Cards in this Set
- Front
- Back
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How are B-cell activated?
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Cross-linking of antigen receptors.
The B-cell receptors on B cells are physically cross-linked by the repetitive epitopes of antigens on the surface of a bacterial cell. It's mostly IgM on naive B cells and is associated with the alpha and beta chains which provide the signaling capacity. |
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What are Thymus-Independent-1 Antigens?
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-They bind to receptors different that BCR
-LPS of Gram negative bacteria bind to CD14 and Toll-like receptor 4 -Induction of IgM production -polyclonal activation |
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What are Thymus-Independent-2 Antigens?
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-Repetitive epitopes (cell wall polysaccharides)
-Activate only mature B-1 cells (strong stimulus for B cells) -No isotope switching-just IgM -No long term immunity -not in infants (response) |
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What are Thymus Dependent Antigens?
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-T cell help is provided
-Isotope switching is induced -Somatic hypermutations encoding the CDRs -Only TD antigens induce immunological help |
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Do B cells need a second signal to proliferate and isotype switch?
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Yes, the B cell signal 2=CD40/CD40 ligand. They need signal 2 to proliferate and cytokines to differentiate into isotype-switched plasma cells.
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What zone are the follicular dendritic cells located?
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Light zone of germinal center .
FDC's present antigen to B cells here. |
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What is the germinal center of a lymph node?
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It's where activated B cells enter lymphoid follicles.
-B cell proliferation -Somatic hypermutation -Selection of antigen-binding |
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How do B cells recognize antigen?
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They recognize antigen as immune complexes bound to the surface of follicular dendritic cells.
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Affinity maturation through somatic hypermutations is initiated by what?
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T-cell cytokines which takes place in centroblasts dividing within the germinal center and gives rise to nondividing centrocytes with mutated surface Ig.
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How are resting and plasma B cells different?
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Plasma cells are terminally differentiated B cells that have a high rate of Ig secretion but no longer divide and specificity can't change. They have no surface receptors, can't induce growth, somatic hypermutation or isotope switching. Resting B cells can.
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What receptor transfers IgG from blood to extracellular spaces?
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FcRB (Brambell receptor)
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How is dimeric IgA antibody transported across epithelia?
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Transcytosis of dimeric (not monomeric) IgA is mediated by poly-Ig receptor on basolateral surfaces of epithelial cells.
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What facilitates the recognition, uptake and destruction of antibody-coated pathogens?
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Phagocyte Fc receptors
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What ligation effect does Fc gamma-RIII receptors have?
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Induction of NK cells.
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What ligation effect does Fc gamma-RI receptors have?
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Activation of respiratory burst and induction of killing.
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What ligation effect does Fc epsilon-RI receptors have?
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Secretion of granules
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What are the 3 pathways of complement activation?
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1. Lectin pathway (innate)
2. Alternative pathway (innate) 3. Classical pathway |
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At what point in complement activation does converging of the pathways happen?
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At the cleavage of complement component C3 into fragments C3b and C3a and the covalent binding of C3b to the pathogens surface.
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What is the most important function of the complement system?
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Complement fixation: where the C3b fragment is bound to the pathogen surface. This C3b tags the pathogen for destruction.
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What protease cleaves C4 in the complement stages?
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C1s (classical pathway)
-It is a serine protease |
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How is the classical pathway of complement initiated?
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By binding of C1q to antibody on bacterial surface.
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What is C4 of the classical pathway of complement?
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C4 is an inactive circulating serine protease that has a thioester bond in the alpha chain protected from hydrolysis.
It gets activated by cleavage of alpha chain by C1s to give fragments C4a and C4b. Some of C4b will be hydrolyzed by water and some will react with the hydroxyl and amino groups on molecules on the pathogens surface. |
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What forms the classical C3 convertase?
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C2 and C4 fragments.
C4b2a (alternatively: C3b/Bb which is the most efficient) |
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What helps clear immune complexes from circulation?
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Erythrocyte CR1 does by the immune complexes bind CR1 on surface of RBC and then they are transported to the liver and spleen.
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What is Decay-Accelerating -Factor?
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DAF is a regulator that prevents bound C4b and C3b fragments from becoming C3 convertases.
It is a defense against complement (human defense). -It is a membrane-bound inhibitor. |
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What inhibits the first stages of the classical pathway of complement activation?
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CI inhibitor (C1INH)
-activated C1r, C1s are susceptible to inhibition by this -soluble inhibitors |
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What are the the anaphylatoxins?
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C3a, C4a, C5a (most stable)
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What membrane-bound inhibitor prevents recruitment of C9 to form the pores/perforations in membranes (C5-C9)?
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CD59
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What complement components are involved in forming the membrane-attack complex?
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C6, 7, 8, 9
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What are some examples of viruses that have an icosahedral symmetry?
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*Herpesvirus (T=16)
-polio (T=1) -Hepatitis B (T=3) Need minimum of 60 proteins so multiply this by their T number. |
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There are 3 general steps in the virus life cycle, what are they?
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1. Attachment, penetration, and uncoating
2. Genome replication and gene expression 3. Assembly and release of progeny |
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What viral component facilitates attachment?
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Viral capsid or envelope (recognize something on host cell surface)
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What host cell surface receptor does the herpes simplex virus recognize?
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Fibroblast Growth Factor
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How does a virus gain entry into the host cell?
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Either by fusion of the cell membrane with the virus envelope or engulfment of the virion by pinocytosis
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How do hard-shell viruses get into the host cell?
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Clathrin-mediated endocytosis and penetration
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How do soft shell viruses get into the host cell?
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Fusion at the cell surface
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Where do DNA viruses replicate?
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In the host nucleus
(except: poxviruses) May use host or viral polymerase to replicate genome. |
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Where do RNA viruses replicate?
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In the cytoplasm
(except retro and influenza viruses) These must use viral polymerase to replicate genome. This RNA-dependent RNA polymerases are not found in cells. |
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What are inclusion bodies indicative of?
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Death
Formation of intranuclear or intracytoplasmic inclusion bodies containing virus particles or proteins to confiscate cell machinery. |
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What does a cell look like when undergoing cytopathic effect?
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-Cell becomes rounded and darkened
-Culminates in cell lysis or syncytia formation |
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What are the steps involved in pathogenesis?
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-transmission and entry
-viral replication and cell damage -dissemination -persistence in some cases -host defense |
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Virulence factors (virokines) allow viruses to cause disease. What do the following viruses inhibit?
1. Vaccinia 2. Herpes 3. HIV 4. EBV |
1. Vaccinia=IL-1 and TNF
2. Herpes=complement 3. HIV=MHC class 1 4. EBV=blocks eIF-2 phosphorylation |
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What is it called when a primary cause of cell death in many infections is due to killing of infected cells by the host immune system?
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Immunopathogenesis
Can be cytotoxic T cell mediated or antibody-mediated complement fixation (hepatitis) |
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What is the purpose of Interferon alpha and beta?
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They are non-specific defenses produced by infected cells to alert nearby cells of infection and reduce their metabolism.
-Induced by the presence of viruses or ds RNA not found in cells ***BLOCK TRANSLATION OF VIRAL MRNA |
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There are 3 things that Interferon alpha and beta induce, what are they?
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1. 2, 5-oligonucleotide synthetase
2. Ribonuclease 3. Protein Kinase |
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What does protein kinase do?
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-phosphorylates and inactivates eIF-2 needed for protein synthesis
-produced by Interferon alpha and beta |
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What does 2, 5-oligonucleotide synthetase do?
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-produced by IF alpha and beta
-Makes a newly transcribed adenine trinucleotide 2, 5-oligo (A) |
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What does ribonuclease do?
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-activated by 2,5-oligo A to degrade viral mRNA
-produced by IF alpha and beta |
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What acts to neutralize virus particles?
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Antibodies: via preventing cell binding, disrupt virion, attract macrophages
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What type of cell culture with putative host cell type provides presumptive identification?
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Characteristic CPE (cytopathic effect)
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Complement fixation with know antibodies, neutralization, fluorescent Ab assay, radio-immune assay, ELISA and electron microscopy are identified by what?
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Definitive ID with no CPE
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Light microscopy is useful in detecting what?
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Inclusion bodies or syncytia
Use immunofluorescence (direct and indirect) |
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What is EM useful for in detection?
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Virus size and morphology
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What are serological tests useful for?
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For infection detection
-If acute infection is detected, initial IgG antibody is titered and compared to later titer (14 days) -4-fold increase=infection -downside: initial IgG cannot distinguish between current and previous infection, need 2 titers -IgM indicates current infection |
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What can ELISA measure?
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Ab titer or level of viral antigen in serum
-Direct (Ag in well) or Indired (Ab in serum attaches to Ag) |
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What test allows for quantitative assessment of viral load?
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Real-time PCR
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Explain the sequence of detecting viral antigens or nucleic acids.
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1. Look for antigens in specimens using ELISA
2. Assay presence of viral genomes or mRNA -use PCR amplification for detection -probe with complementary cDNA/cRNA or sequence directly -RT-PCR for assessing viral load |
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What 2 types of antiviral drugs are effective?
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1. Nucleoside analogues
2. Protease inhibitors |
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What is the mechanism of nucleoside analogues?
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-They mimic and compete with normal nucleosides (bases)
-They act to inhibit DNA synthesis (termination) or cause lethal errors (mutations) by creating base-pair mismatches -rely on variable affinity of host cell versus viral enzymes and polymerases |
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What are the 3 main nucleoside analogues used against viruses?
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Acylovir and Gancyclovir: herpes
Azidothymidine against retroviruses |
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What is Acylovir effective against?
What type of analogue is it? |
HSV and VZV
-also drug of choice for HSV-1 encephalitis or compromised hear -It is a Guanosine analogue that is missing the 2' and 3' carbons |
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What is the mode of action of Acyclovir?
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1. Can be phosphorylated by viral thymidine kinase to yield acyclovir monophosphate.
2. Monophosphate is then converted to triphosphate by host enzymes 3. Incorporation of acyclovir triphosphate into DNA synthesis result in chain termination in viral infected cells (b/c no 3' carbon) |
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Why isn't Acylovir effective against latent viruses?
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Because host cell thymidine kinase cannot phosphorylate. Need
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What is the mode of action of Gancyclovir?
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Similar to acyclovir but only missing 1 carbon
-Used against the cytomegalovirus |
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How is AZT different than Gancyclovir and Acyclovir?
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AZT is a thymidine analogue
-It is an anti-retroviral drug, because viral reverse-transcriptase has lower selectivity (greater sensitivity). |
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What does a protease inhibitor do?
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It inhibits proteolytic maturation of the HIV nucleocapsid by mimicking a polypeptide.
Eg: Saquinavir |
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2 types of vaccines generate active immunity, what are they? Which is more effective?
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1. attenuated virus: (non-virulent, but can replicate without pathology)
2. killed virus (injected IM) Live is better b/c it has longer antigenic stimulus to multiply and persist in the host. It has both IgG and IgA, produces a cell-mediated response and has a longer span of immunity but can be risky due to risk of reversion to virulence. |
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What are 2 examples of passive immunizations and when is it done?
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-Vaccine given post-exposure
-Usually IgM 2 examples: Rabies IG (RIG) Hepatitis (HBIG) |
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What is the structure of Herpesvirus?
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-Large icosahedral core with a lipoprotein envelope derived from the nucleus
-Large linear dsDNA with no viral polymerase -Replicates in nucleus |
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Which herpesviruses cause vesicular rashes and which do not?
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HSV & VZV=vesicular rash
EBV & CMV=no rash |
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What is the mechanism of HSV replication?
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1. Attachment (viral envelope proteins) to fibroblast growth factor on cell surface
2. After uncoating, DNA enters the nucleus where it is transcribed by host RNAP 3. DNA is replicated, late genes expressed 4. Proteins go to nucleus to form new viral genomes. 5. Capsids bud through nuclear membrane and exit cell via tubules or vacuoles. |
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Latency of HSV is in sensory ganglia in which areas for HSV-1 and HSV-2?
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HSV-1=trigeminal
HSV-2=sacral and lumbar ganglia |
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What are the 7 infections that can be induced by HSV-1?
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-primary gingivostomatitis
-herpes labialis -keratoconjuctivitis -encephalitis (temporal lobe): high mortality -herpetic whitlow -disseminated infections -bell's palsy |
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What are the 3 infections that can be induced by HSV-2?
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-genital herpes
-neonatal herpes -mild aseptic meningitis |
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What test do you do to detect multinucleated giant cells in HSV diagnosis?
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Tzanck smear
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What test do you do to detect HSV?
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Cell culture CPE in 1-3 days
-do IFAB or -ELISA: for virus glycoprotein detection |
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What drug do you use for orolabial HSV-1?
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Penciclovir
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What drug to you use for genital infection HSV?
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Valacyclovir and Famciclovir
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What drug do you use for HSV-1 in the eye?
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Trifluridine
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Where does VZV become latent?
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Dorsal root ganglion
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What drugs do you treat VZV with?
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Acyclovir and Immune globulin
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What virus is the most common cause of congenital abnormalities?
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Cytomegalovirus
-1/750 births |
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What do you treat cytomegalovirus with? How is it detected?
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Gancyclovir treatment
PCR or Ab titre |
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Where does the Epstein-Barr Virus remain latent?
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-Infects B lymphocytes primarily and targets the C3 receptor
- |
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What virus can associate with Burkitt's lymphoma, nasopharyngeal carcinoma and hairy leukoplakia?
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Mononucleosis: EBV
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What test is done for EBV?
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Monospot test for heterophil Ab
-No treatment -IgM and IgG reacts against viral capsid antigen (VCA) |
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What drugs do you use to treat chronic hep B?
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Nucleoside analogues and alpha-interferon
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What genome is HAV considered?
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ssRNA
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What genome is HBV considered?
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dsDNA (interrupted circular DNA)
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What genome is HCV considered?
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ssRNA
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What genome is HDV considered?
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ssRNA
(circular, negative stranded) |
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What hepatitis has DNA polymerase in the virion and HBsAG in the envelope?
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HBV
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What 2 types of hepatitis infections have HBsAg in their envelope?
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HBV, HDV
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What hepatitis infections have chronic carriers?
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HBV, HCV, HDV
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What hepatitis infections have vaccines available?
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HAV, HBV
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What hepatitis infections have useful Immune Globulins?
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HAV, HBV
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What laboratory test is useful in diagnosing HAV?
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IgM HAV
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What laboratory test is useful in diagnosing HBV?
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HBsAg, HBsAb, IgM HBcAb
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What laboratory test is useful in diagnosing HCV?
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HCV Ab
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What laboratory test is useful in diagnosing HDV?
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Ab to delta Ag
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What laboratory test is useful in diagnosing HEV?
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None
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What type of genome is HIV?
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retrovirus, enveloped, ss RNA
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What is p24 capsid protein a marker for?
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HIV detection
gag=structural gene that codes the protein |
