House Majority Leader Eric Cantor’s astonishing defeat to Republican primary candidate David Brat Tuesday night upends the national political landscape, carrying profound implications for immigration reform and the Republican party.

1. John Boehner’s speakership is up for grabs

The race to succeed Speaker John Boehner is now wide open. Boehner recently said he’s “living on borrowed time” when asked if he’ll serve a third full term as Speaker. And Cantor, his deputy and natural successor, was the clear favorite to succeed him. One member being drafted by the tea party to leapfrog Cantor for the speakership is conservative Rep. Jeb Hensarling (R-TX), who has been coy about his intentions. With Cantor out of the running, the equation changes for Hensarling as well as others who may want to run for the position — perhaps also for Boehner in his decision about when to step down.

2. Republicans will be more terrified of immigration reform

House Republicans will now be even more terrified of immigration reform. The argument that they can support an overhaul without imperiling their status with conservatives back home just took a huge hit. It’s true, as the pro-reform community rushed to point out, that Cantor was hardly a champion of their cause. But that’s not how the House GOP will perceive this development. Cantor’s endorsement in January of a set of broad “principles” that included legal status for the undocumented turned him into a piñata for the right and galvanized opposition to him in his renomination bid. This is the same wing of the party that decides GOP primaries and can vote out any other Republican who dares to go down that road.

3. And that may cost the GOP the presidency in 2016

That means Republicans may be toast in 2016. Without passage of immigration reform, most Hispanic voters won’t consider voting for a Republican candidate, as Chamber of Commerce President Tom Donohue and Sen. John McCain (R-AZ) have argued. That suggests the party is in deep trouble in the next presidential election where Latinos will play a major role.

4. Establishment Republicans are no longer trouncing the right

The resurgence of the GOP establishment just took a devastating blow. So far 2014 has been marked by entrenched Republicans wresting back control of GOP from the rambunctious tea party. Cantor’s stunning loss disrupts that narrative and puts every incumbent Republican on notice that they may be next. Any comfort from the string of victories for establishment-favored candidates so far in the primaries will evaporate on Tuesday night. RedState.com blogger Erick Erickson wrote, “[Cantor] kept his attention off his district, constituents, and conservatives while he and his staff plotted to get the Speaker’s chair.”

5. The tea party is emboldened

The anti-establishment wing of the GOP scored a grand prize just when it was on the ropes and desperately needed a victory. Ousting Cantor emboldens outside conservatives with a bully pulpit to taunt the establishment wing. How long it will last remains to be seen. Right-wing radio host Mark Levin, a Brat supporter, said Tuesday night on Fox News that Cantor’s defeat means Republicans should “stop chasing ethnic groups, stop chasing genitalia” and instead listen to conservatives.

6. National Republicans will be very afraid

The result comes as an electric shock to all major national party leaders, who tend to have huge fundraising advantages at the tips of their fingers and, as a result, sometimes take their constituents for granted. True, it’s not the first time a member of congressional leadership has lost reelection. But, quite remarkably, Cantor is the first House majority leader to lose his renomination bid in U.S. history — or more specifically since the office was created in 1899, according to the University of Minnesota’s SmartPolitics blog.