Practice question

Live attenuated vaccines comprise pathogens weakened laboratory passage serial passage heterologous hosts chick embryo fibroblasts 100 times cold adaptation growth 25C restrictive temperature-sensitive polymerase mutations or targeted deletions removing virulence determinants NS1 influenza inhibiting interferon thymidine kinase herpes limiting replication neurons capsule genes retaining ability infect host cells particularly epithelial dendritic cells transcribe viral genes under cellular Pol II produce antigens near wild-type assemble virions replicate transiently low levels limited host innate immunity without clinical disease impaired antagonism interferon. Intracellular replication triggers cytosolic dsRNA sensors RIG-I recognizing 5 triphosphate RNA MDA5 long dsRNA inducing MAVS aggregation activating IRF3 NF-kB generating antiviral state type I IFN beta inflammasome NLRP3 caspase-1 cleaving IL1beta providing potent intrinsic adjuvant mimicking natural infection. Antigen synthesized endogenously enters ER translocon SEC61 loading TAP nascent MHC I heavy beta2 microglobulin presenting CD8 CTL critical intracellular bacteria TB viruses CMV while exogenous release stimulates MHC II. Mucosal IgA induced administered orally oral polio Sabin or intranasally live attenuated influenza FluMist homing lamina propria plasma secreting secretory IgA. In contrast inactivated vaccines killed chemical treatment formalin 0.02 percent 28 days crosslinking proteins beta-propiolactone alkylating nucleic acids heat 56C denaturing