Adult t cell leukemia atl large numbers of

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Adult T-cell Leukemia (ATL):large numbers of lymphocytes,skin lesions, lymphadenopathy,hepatosplenomegaly; relativelyindolentTropical Spastic Paraperesis(TSP): demyelinationof longmotor neurons, stiff gait withspasticity and hyperreflexia,Infects most non-dividing cells,but does not transform. Chronicpersistent infection due toability to escape immunecontrolHuman RetrovirusesHIVViralCharacteristicsEnvelopedNegative polarity ssRNAgenomeDiploidRetrovirus: ssRNAreverse transcribed to generate dsDNA, followed byintegration into the host genome as pro-virusPathogenesisTargets: CD4+ T lymphocytes (GALT, lymph nodes, spleen, thymus),macrophages, dendriticcells, brain macrophages and microgliaDifferent anatomical sites often harbor distinct, but phylogeneticallyrelated HIV-1 genotypes due to tissue-specific target cell characteristics, immunologicalpressures, and antiretroviral penetrationNatural HistoryVirus expands with a doubling time of 12 hours; about 1011particles generateddailyAcute infection (14-21 days post exposure): 1-100 million viral particles; may beasymptomatic or have meningitis, fever, rashT cell response reduces viral load, resulting in a chronic infective steady statelevel that depends on host HLA haplotype(production = clearance)Over time, CD4 cell count is gradually depleted due to cytolyticviral production,increasing susceptibility to opportunistic infections . Plasma viral RNA reflects therate of CD4 cell decline.ClinicalManifestationsHIV –associated neurological disorders (HAND) in 50% of untreated patientsGALT has memory T-cells (because constantly exposed to antigen) that expressCCR5, the co-receptor that makes it universally infectable. As a result, all of theGALT is depleted in acute infectionAs CD4 cell counts decline, more infections with pathogens that are inherentlyspasticity and hyperreflexia,lower extremity weakness,urinary incontinence, sensoryneuropathyTransmissionVertical,via breast milkBloodSexSexBloodPerinatalTreatmentATL: cytotoxicchemotherapywith steroidsTSP: corticoor androgenicsteroidsNOT ARTARTRetrovirus Genesgag: internal structuralgenespol: genes for protease,reverse transcriptaseenv: envelope genes(accessory genes inlentiviruses)2 terminal repeatsAs CD4 cell counts decline, more infections with pathogens that are inherentlyless virulentHost ResponseSome antibodies directed against HIV envelope can neutralize virions; but therapid changes in HIV make vaccine development difficultCytotoxicT lymphocytes and specific HLA haplotypescan determine whetherprogression is rapid or slow; heterozygoteshave a better prognosis thanhomozygotesCD4+ Helper cells are important, but these are destroyed by HIV with timeHIV Accessory GenesVifInhibits host cell apobec3G/3F(which deaminatescytosinesin the viral DNA, leading to Gbarb2rightA hypermutationanddegradation) by inducing proteasomaldegradation of apobec3G/3F.

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Term
Spring
Professor
staff
Tags
Bacteria, Escherichia coli, gram negative bacteria, GI Tract, Gram positive bacteria

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