A virus that appeared in the last episode is affecting all the humans. The only people who can catch the virus are humans and Irathiens. A meeting is called by Defiance council where after a secret vote, it is decided that Irathiens are quarantined to prevent the virus spreading. Irathiens are primary sources of the virus although they can't be killed by the virus.
After the vote, Rafe McCawley starts to round up all the Irathiens and that includes Irisa. Jeb Nolan tries to prevent the miners who are rounding the Irathiens up from taking Irisa but it no use, Irisa is taken away.
An S.O.S. is sent out to other communities for the cure, San Francisco announces that they will send over supplies which they carry out. The supplies land outside the city limits but the city has been quarantined by the Earth Republic.
Jeb Nolan finds and orders Connor Lang to help him to get the cure back. Earth Republic troopers have the city surrounded and won't let anyone in or out. Jeb and Connor try to persuade the Earth Republic to let them through and it turns out that Oflin is coordinating the quarantine. Jeb manages to get the superior officer to let them through to get the supplies, overruling Oflin.
Quentin McCawley has given Nicky the object that shes been after, in return Nicky tells Quentin about his mother. Quentin's mother and Rafe's wife is alive in Mendecino and is suffering from bipolar disorder. Quentin McCawley decides to go find his mother.
When Jeb and Connor return to Defiance, their tyres are blown out and they are captured by some Irathiens who had managed not to get caught. The leader of the Irathiens wants his brother whose dead. The brother had been killed earlier in a fight at the camp holding the Irathiens.
With Amanda Rosewater too ill to do anything, Datak Tarr takes on the duties of the Mayor. Datak Tarr turns up at the kidnappers hideout and pretends to side with the Irathiens but turns on them and kills them. After Connor helps free Datak Tarr who the Irathiens have turned on, Datak kills Connor because he knows the truth. Datak decides not to kill Jeb Nolan as he didn't see what had happened.
At a daily broadcast from the top of the arch, Datak Tarr announces he will run for Mayor against Amanda Rosewater.
At the end, Nicky has a secret meeting with Doc Yewll where Nicky asks the Doctor to join her in her plans.
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