In immunology, an antigen is a substance that evokes the production of one or more antibodies. Each antibody binds to a specific antigen by way of an interaction similar to the fit between a lock and a key. The substance may be from the external environment or formed within the body. The immune system will try to destroy or neutralize any antigen that is recognized as a foreign and potentially harmful invader. The term originally came from antibody generator^[1][2] and was a molecule that binds specifically to an antibody, but the term now also refers to any molecule or molecular fragment that can be bound by a major histocompatibility complex (MHC) and presented to a T-cell receptor.^[3] "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens can be identified as invaders and can be attacked by the immune system.

An immunogen is a specific type of antigen. An immunogen is a substance that is able to provoke an adaptive immune response if injected on its own.^[4] An immunogen is able to induce an immune response, whereas an antigen is able to combine with the products of an immune response once they are made. The overlapping concepts of immunogenicity and antigenicity are, therefore, subtly different. According to a current textbook:

Immunogenicity is the ability to induce a humoral and/or cell-mediated immune response

Antigenicity is the ability to combine specifically with the final products of the immune response (i.e. secreted antibodies and/or surface receptors on T-cells). Although all molecules that have the property of immunogenicity also have the property of antigenicity, the reverse is not true."^[5]

At the molecular level, an antigen is characterized by its ability to be "bound" at the antigen-binding site of an antibody. Note also that antibodies tend to discriminate between the specific molecular structures presented on the surface of the antigen (as illustrated in the Figure). Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Non-microbial exogenous (non-self) antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on the surface of transfused blood cells. Vaccines are examples of immunogenic antigens intentionally administered to induce acquired immunity in the recipient.

Cells present their immunogenic-antigens to the immune system via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of immune cells can become activated.

Related concepts[link]

• Epitope - The distinct molecular surface features of an antigen capable of being bound by an antibody (a.k.a. antigenic determinant). Antigenic molecules, normally being "large" biological polymers, usually present several surface features that can act as points of interaction for specific antibodies. Any such distinct molecular feature constitutes an epitope. Therefore, most antigens have the potential to be bound by several distinct antibodies, each of which is specific to a particular epitope. Using the "lock and key" metaphor, the antigen itself can be seen as a string of keys - any epitope being a "key" - each of which can match a different lock. Different antibody idiotypes, each having distinctly formed complementarity determining regions, correspond to the various "locks" that can match "the keys" (epitopes) presented on the antigen molecule.

• Allergen - A substance capable of causing an allergic reaction. The (detrimental) reaction may result after exposure via ingestion, inhalation, injection, or contact with skin.
• Superantigen - A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T cell activation and massive cytokine release.
• Tolerogen - A substance that invokes a specific immune non-responsiveness due to its molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
• Immunoglobulin binding protein - These proteins are capable of binding to antibodies at positions outside of the antigen-binding site. That is, whereas antigens are the "target" of antibodies, immunoglobulin-binding proteins "attack" antibodies. Protein A, protein G, and protein L are examples of proteins that strongly bind to various antibody isotypes.

Origin of the term antigen[link]

In 1899, Ladislas Deutsch (Laszlo Detre) (1874–1939) named the hypothetical substances halfway between bacterial constituents and antibodies "substances immunogenes ou antigenes". He originally believed those substances to be precursors of antibodies, just like zymogen is a precursor of an enzyme. But, by 1903, he understood that an antigen induces the production of immune bodies (antibodies) and wrote that the word antigen is a contraction of "Antisomatogen = Immunkörperbildner". The Oxford English Dictionary indicates that the logical construction should be "anti(body)-gen".^[6]

Origin of antigens[link]

Antigens can be classified in order of their class.

Exogenous antigens[link]

Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. The immune system's response to exogenous antigens is often subclinical. By endocytosis or phagocytosis, exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4⁺) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines. Cytokines are substances that can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and other particles.

Some antigens start out as exogenous antigens, and later become endogenous (for example, intracellular viruses). Intracellular antigens can be released back into circulation upon the destruction of the infected cell, again.

Endogenous antigens[link]

Endogenous antigens are antigens that have been generated within previously-normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8⁺ T cells recognize them, the T cells begin to secrete various toxins that cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins, self-reactive T cells are deleted from the repertoire as a result of tolerance (also known as negative selection). Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous) antigens.

Autoantigens[link]

An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens should, under normal conditions, not be the target of the immune system, but, due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in these patients.

Tumor antigens[link]

Tumor antigens or neoantigens are^{[citation needed]} those antigens that are presented by MHC I or MHC II molecules on the surface of tumor cells. These antigens can sometimes be presented by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and, in general, result from a tumor-specific mutation. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy the tumor cells before they proliferate or metastasize.

Tumor antigens can also be on the surface of the tumor in the form of, for example, a mutated receptor, in which case they will be recognized by B cells.

Nativity[link]

A native antigen is an antigen that is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they be processed by APCs, whereas B cells can be activated by native ones.

Antigenic specificity[link]

Antigen(ic) specificity is the ability of the host cells to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision. Antigen specificity is due primarily to the side-chain conformations of the antigen. It is a measurement, although the degree of specificity may not be easy to measure, and need not be linear or of the nature of a rate-limited step or equation.^[7]

See also[link]

• Epitope
• Linear epitope
• Conformational epitope
• Original antigenic sin
• Polyclonal B cell response
• Magnetic immunoassay
• Priming (immunology)

Notes[link]

External links[link]

• Antigen Retrieval Protocol
• Immunology
• National Library of Medicine/Medline (National Institute of Health) website

Andrea Martin
Martin in June 2008
Born	Andrea Louise Martin (1947-01-15) January 15, 1947 (age 65) Portland, Maine, U.S.
Occupation	Actress/Comedienne
Years active	1969—present
Spouse	Bob Dolman (m. 1980 - divorced; 2 children)

Andrea Louise Martin (born January 15, 1947) is an American and Canadian actress and comedienne.^[1][2] She has appeared in films such as My Big Fat Greek Wedding, on stage in productions such as My Favorite Year, Fiddler on the Roof and Candide, and in the television series, SCTV.

Personal life[link]

Martin, the oldest of three children, was born in Portland, Maine,^[3] in 1947, the daughter of Sybil A. (née Manoogian) and John Papazian Martin.^[4] Her paternal grandparents were Armenian immigrants who moved to the U.S. from Turkey to escape the Armenian Genocide.^[5][6][7] Her father owned Martin's Foods, a grocery store chain.^[8] Her maternal grandparents were Armenians from Yerevan and Istanbul.^[9]

She has two sons, Jack (born ca. 1980) and Joe (born 1983), with ex-husband Bob Dolman, a screenwriter. Through this marriage, she was the sister-in-law of Dolman's sister, actress Nancy, and her husband Martin Short.^[10]

Career[link]

Soon after graduating from Emerson College, she won a role in a touring company of You're A Good Man, Charlie Brown. After frequent visits to Toronto, she relocated from New York City to Toronto in 1970 and immediately found steady theater work.

In 1972, she played the character of Robin in a Toronto production of Godspell, with a cast that included future comedy stars Gilda Radner, Martin Short, Eugene Levy, singer and actor Victor Garber, and musical director Paul Shaffer. Two of her first prominent film roles were in 1973's Cannibal Girls and then as the bookish sorority sister Phyllis in Black Christmas, another Canadian slasher film from 1974.

Two years later, she joined then-unknowns John Candy, Dave Thomas, Eugene Levy, Catherine O'Hara, Harold Ramis and Joe Flaherty on the Canadian sketch comedy television series, SCTV, which was set at fictional television station "Second City Television", or SCTV, in Melonville. Martin most notably portrayed leopard-print-wearing station manager Edith Prickley, whose dealings with the staff, including president/owner Guy Caballero, clueless newscaster Earl Camembert, and washed-up actor Johnny LaRue, helped to provide much of the show's humor. Her other memorable characterizations included repressed sexologist Dr. Cheryl Kinsey, insecure self-affirmation guru Libby Wolfson, pidgin-tongued janitress Pirini Scleroso, tone-deaf children's entertainer Mrs. Falbo, Texan curio pitchwoman Edna Boil, and impossibly tight-jeaned Melba, the Disco Queen. Her talent for impersonation was key in her humorous portrayals of such luminaries as Barbra Streisand, Ethel Merman, Arlene Francis, Pauline Kael, Sally Field, Sophia Loren, Beverly Sills, Lynn Redgrave, Linda Lavin, Bernadette Peters, Liza Minnelli, Connie Francis, Mother Teresa, Alice B. Toklas, Patti Smith, Brenda Vaccaro and Indira Gandhi.^[11]

Her 1970s stage work eventually included the Toronto branch of the improvisational comedy troupe The Second City, a group which produced almost the entire cast of SCTV. In 1992, she made her Broadway debut in the musical My Favorite Year, for which she won the Tony Award, Theatre World Award, and Drama Desk Award for Best Featured Actress in a Musical. Additional Broadway credits include Candide (1997) and Oklahoma! (2002)—both of which brought her Tony nominations—and Fiddler on the Roof (2005). She appeared in the Broadway premiere of Young Frankenstein (2007) as Frau Blucher, leaving the cast on July 6, 2008.^[12]

Martin starred alongside Geoffrey Rush and Susan Sarandon in the Broadway revival of Exit the King which played at the Ethel Barrymore Theatre from March 7 to June 14, 2009.^[13] She wrote and performed in the critically acclaimed one-woman show Nude, Nude, Totally Nude in Los Angeles and New York City,^[14] receiving a 1996 Drama Desk Award for Outstanding One Person Show.

Other theater credits include the leads in The Rose Tattoo and Betty's Summer Vacation, both produced at The Huntington Theatre in Boston. Martin has played Wanda the Word Fairy in numerous short segments on Sesame Street She appeared in one episode from Season 5 (1988) titled "UNICEF". Star Trek fans may recognize her as one of two actresses to play Ishka, Quark's iconoclastic mother on Star Trek: Deep Space Nine. For her role, she was made up to appear as an older woman although in reality Martin is less than three years older than Armin Shimerman, who played Quark. She only played the role of Ishka once—finding the prosthetics involved to be uncomfortable Martin declined to return, and Cecily Adams was hired to play Ishka in all future appearances.

She has won two Emmy Awards for Outstanding Writing in a Variety or Music Program in 1982 and 1983. She has done considerable voice work in such animated film and television productions such as Anastasia, Jimmy Neutron: Boy Genius, The Grim Adventures Of Billy And Mandy, The Simpsons (as Apu's mother), Recess as Lunchlady Harriet, the 1999 version of The Woody Woodpecker Show, Earthworm Jim, Kim Possible, SpongeBob SquarePants, and Brother Bear 2. She also appeared in the 1993 television adaptation of Gypsy starring Bette Midler.

Her many screen credits include Wag the Dog, All I Want for Christmas, Hedwig and the Angry Inch, Stepping Out, The Producers, and My Big Fat Greek Wedding, in which she portrayed Aunt Voula, a role she reprised in the short-lived small-screen adaptation. In 2006, she played a major role in the remake of Black Christmas. In the episode titled Pupil, she played an emergency room patient on the Showtime series, Nurse Jackie, which was aired July 27, 2009.

References[link]

External links[link]

Wikimedia Commons has media related to: Andrea Martin

• Andrea Martin at the Internet Movie Database
• Andrea Martin at the Internet Broadway Database
• Andrea Martin at Memory Alpha (a Star Trek wiki)
• Andrea Martin—Downstage Center interview at American Theatre Wing.org
• Andrea Martin biography/filmography at northernstars.ca
• Andrea Martin Official Website - Launched April 2011