There’s a moment in the final episode of Dead to Me, Netflix’s dark comedy about best friends, murder, and a luxurious backyard pool, where a terminally ill Judy (Linda Cardellini) lies in bed alongside her partner in crime, Jen (Christina Applegate), and says, “I’ve had the best time.” To which Jen replies, “I know. Me too.” You’d have to be acutely dehydrated to not well up.

For Applegate, the tears flowed on that final day on set, and again when she revisited the memory last week during this interview. “It was knowing the journey the two of us had been on, not just as those characters, but as two dear friends and acting partners,” she said.

It’s hard not to look at that scene as another goodbye, with Applegate now saying she may leave behind acting on camera because of the challenges of living with multiple sclerosis. Nearly two years after her diagnosis (she found out she had MS while filming Dead to Me’s final season) and less than a week after a hospital stay, she looked back at the show’s final season, paying tribute not just to Cardellini but also to James Marsden, who played twins on the show, and the show’s creator, Liz Feldman. Excerpts from a conversation with an icon who’s utterly honest and zero-fucks-to-give-funny.

Vanity Fair: The final season of Dead to Me came out late last year but it’s back in the conversation because of the first Emmy-voting window. Does the show feel like a lifetime ago, or do you still think about Jen?

Christina Applegate: It feels like a hundred years ago at this point, just because it kind of was, and it was such a trying and taxing time for me to even film. So I think I just had to get away from it all, you know? I miss my friends. I miss Linda. I miss Liz. I miss James. I miss the experience of it, but at the same time, because it was such an incredible struggle this last year, I’m relieved that I no longer have to push so hard to get through my day.

How are you feeling today?

With the disease of MS, it’s never a good day. You just have little shitty days. People are like, “Well, why don’t you take more showers?” Well, because getting in the shower is frightening. You can fall, you can slip, your legs can buckle. Especially because I have a glass shower. It’s frightening to me to get in there. There are just certain things that people take for granted in their lives that I took for granted. Going down the stairs, carrying things—you can’t do that anymore. It fucking sucks. I can still drive my car short distances. I can bring up food to my kid. Up, never down.

Because MS affects your balance?

Yeah, and gravity can just pull you down and take everything down with you. So we have this little thing at the top of the stairs that we call “purgatory.” So if anyone’s done with anything upstairs, we put it in purgatory so one of my able friends can bring it downstairs.

You have a group of able friends who come by to help out?

No. I know that sounds like, “Yay!” But I actually don’t want to be around a lot of people because I’m immunocompromised. I have my friend who lives here during the week and she helps me take care of [12-year-old daughter] Sadie. And then on the weekend I have a caretaker. I also don’t want a lot of stimulation of the nervous system because it can be a little bit too much for me. I like to keep it as quiet and as mellow as possible.

Sometimes even the most well-meaning visitors…

It’s exhausting. Imagine just being in a crowd of people and how loud that is. It’s like 5,000 times louder for anyone who has lesions on their brains.

There are moments this season where we watch Linda’s character, Judy, battle a disease while knowing that in real life you are actually the person battling one. In one scene, Jen is looking in the mirror and talking to her reflection about troubling shadows on a scan. It felt very meta to watch. How was it to play those moments?

It was bizarre. Especially since the season was written over a year before this all was shot. So it was almost like a portent. None of us knew I was going to be sick and gain 40 pounds from medication and have immobility. It was really difficult to not have my own personal feelings shadow what Jen was feeling. A lot of the words were really difficult to say and a lot of the scenes were really difficult to do. I had to keep remembering that this is Judy’s disease. It was really hard to not take that on, especially when the words were so cathartic and so right-to-the-bone.