CHICAGO — Harold Ramis, the bespectacled Ghostbusters sidekick to Bill Murray whose early grounding in live comedy led to blockbuster movies such as National Lampoon’s Animal House, Caddyshack and Groundhog Day, died Feb. 25. He was 69.

Ramis, who suffered for several years from an autoimmune disease that caused inflammation and damage to his blood vessels, died at his home in the Chicago suburbs, surrounded by family and friends, his talent agency said.

The writer-director-actor quietly and often off-screen created an unparalleled and hugely influential body of laughs in a filmography that includes some of the most beloved and widely quoted comedy classics of the last 30 years.

His death rattled a modern comedy world Ramis helped build. His legacy as a father figure to generations of comedians was appropriately captured in Judd Apatow’s Knocked Up, in which Ramis was cast as Seth Rogen’s father, he said, “because we all saw him as the dream dad.”

“Harold Ramis made almost every movie which made me want to become a comedy director,” Apatow said. “These films are the touchstones of our lives.”

Chevy Chase, whom Ramis directed in Caddyshack and National Lampoon’s Vacation, called him “a great man who shunned unnecessary Hollywood-type publicity.”

“It was Harold who acted out and gave me the inspiration for the character of Clark Griswold” in the National Lampoon Vacation movies, Chase said. “I was really copying Harold’s impression of Clark.”

Admittedly lacking the dashing leading-man looks of some of his peers, Ramis was memorably nebbishy: curly haired, gangly and bespectacled. He played Ghostbuster scientist Egon Spengler (naturally, the one with all the ideas), and Bill Murray’s Army recruit buddy in Stripes.

But the Chicago native and early member of the improv comedy troupe Second City was a far larger force behind the camera. The intellectual Ramis was the Zen master to a wild, improvising comic storm that included Murray, John Belushi, Chase and Dan Aykroyd.

He co-wrote and directed Caddyshack, Groundhog Day, and Analyze This. He helped pen Meatballs, Stripes and Ghostbusters.

Ramis could reasonably be credited with making more people roll in the aisles from the late 1970s to the early 1990s than almost anyone else. “He earned his keep on this planet,” Murray said in a statement.

With a Baby Boomer countercultural bent, Ramis — who escaped Vietnam service, he claimed, by checking every box on the medical-history form — pushed against institutions: the college dean of Animal House, the country club members of Caddyshack, the drill sergeant of “Stripes.”

Ramis, who became a Buddhist in midlife, was known to have a spiritual pull, on full display in the wry but earnest existentialism of Groundhog Day (1993), in which Murray re-lives a day until he finally gets it right. His Ghostbusters co-star and Second City mate Aykroyd said: “May he now get the answers he was always seeking.”

The son of Chicago shopkeepers, Ramis was born Nov. 21, 1944. After graduating from Washington University in St. Louis, he briefly worked in a mental institution. He often said, seriously, that the experience helped prepare him for working with actors.

Ramis would help recalibrate the epicenter of American comedy at Second City, which he joined in 1969. He was soon followed by many of his later collaborators: Belushi (Animal House), Murray and Aykroyd. In 1976, he became head writer for the Canadian-based comedy show Second City Television, or SCTV.

Chicago, he later said in the book of interviews And Here’s the Kicker, conditioned him to living “slightly on the outside of the mainstream.”

“New York and L.A. were the real centers of culture in America, and we were kind of a sideshow,” said Ramis. “There’s always more comedy in being alienated than in fitting in.”

He soon moved on to bigger projects — the legendary 1978 comedy National Lampoon’s Animal House, which he wrote with National Lampoon co-founder Doug Kenney. Their motto was “broad comedy is not necessarily dumb comedy.”

With Murray as the comic lead, the Second City alums paired up for numerous projects: 1979’s Meatballs, 1980’s Caddyshack and 1981’s Stripes. The Cinderella story scene in Caddyshack came from Ramis suggesting that Murray talk to himself like a sports announcer.

Though Ramis had once harbored lead actor dreams, he realized his better fit was as a straight man or a director of more uninhibited talents like Belushi or Murray. “As a person of intellect, I could complement John or Bill, who were people of instinct; I could help guide and deploy that instinct,” he told The New Yorker magazine in 2004.

Perhaps the most well-known of his collaborations with Murray and Aykroyd was Ghostbusters, which became one of the biggest hits of the 1980s. Ramis helped write the 1984 movie, in which he stars as the commonsense member of a group of parapsychologists who try to catch ghosts.

“The best comedy touches something that’s timeless and universal in people,” Ramis told The Associated Press in a 2009 story about the 50th anniversary of Second City. “When you hit it right, those things last.”

After Groundhog Day, Ramis and Murray fell out and didn’t speak for years. The cause of the rupture between the pair, one of the most storied actor-director teams in comedy, isn’t widely known, as neither ever spoke much publicly about it. The Chicago Tribune reported that Murray visited Ramis during his illness.

Ramis’ last hit was Analyze This (1999), the therapist-meets-mobster comedy starring Billy Crystal and Robert DeNiro. Like many of his later films (1996’s Multiplicity, 1995’s Stuart Saves His Family), it hinged on a story of personal redemption.

Some of his last efforts (2000’s Bedazzled, 2009’s Year One) were notable flops. The Ice Harvest, a 2005 comedy starring John Cusack, was one of the darkest comedies for Ramis, whose humor — however full of rebellion and absurdity — was nearly always optimistic. A third Ghostbusters with director Ivan Reitman has long been rumored, but is yet to materialize in any substantial way.

Ramis is survived by his wife, Erica; sons Julian and Daniel; daughter Violet; and two grandchildren.

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By Tammy Webber. AP writers Don Babwin in Chicago, and Jessica Herndon in Los Angeles contributed to this report.