Alcohol’s Contribution to Compromised Immunity GYONGYI SZABO, M.D., PH.D. Alcoholics frequently suffer from infectious diseases and have increased rates of some cancers, indicating that alcohol impairs the immune system, which protects the body against this type of damage. Alcohol interferes with the functions of many of the cells and molecules that are part of the immune system. For example, alcohol inhibits the functions of the cells that ingest and destroy invading microorganisms (i.e., neutrophils, monocytes, and macrophages). Both acute and chronic alcohol exposure also alter the production of signaling molecules that help coordinate the immune response (i.e., cytokines). Finally, alcohol adversely affects the functions of the cells that mediate the immune response against specific microorganisms and long-term immunity (i.e., T cells and B cells). As a result, alcoholics have an increased susceptibility to diseases caused by bacterial infections, such as tuberculosis and pneumonia. Alcoholics also may be more susceptible to infections from the virus that causes AIDS. In addition, alcohol intoxication can exacerbate the immune suppression that occurs after traumatic injuries. KEY WORDS: immune system; immune disorder; immune response; AODE (alcohol and other drug effects); cytokines; inflammation; oxygen radicals; bacterial disease; HIV infection; trauma; injury; pathologic process; literature review he immune system serves as the increased risk of developing tumors, THE IMMUNE SYSTEM—AN body’s defense against infections particularly in the head, neck, and OVERVIEW Tby microorganisms; damage upper gastrointestinal tract. Although caused by other foreign substances; alcohol-induced malnutrition—includ- The immune system has two main and the uncontrolled, tumorous growth ing vitamin deficiencies—and ad- arms: innate, or nonspecific, immunity of the body’s own cells. Impairment of vanced liver cirrhosis likely contribute and acquired, or specific, immunity. this system can increase a person’s to some abnormalities in the immune Innate immunity exists before the risk for developing various illnesses, system of alcoholics, alcohol itself body is exposed to a pathogen for the including infectious diseases, such as also is a potent modulator of immune first time. Moreover, this system does tuberculosis, and certain types of can- functions. Interestingly, not only not respond to specific pathogens but cer. Alcohol can modulate this de- chronic alcohol abuse but also single- instead responds to any pathogen it fense, and clinicians have known for a episode (i.e., acute) and/or moderate encounters. For example, the cells long time that chronic alcohol abusers alcohol consumption can affect the involved in innate immunity immedi- have an impaired immune system. immune system. ately attack any kind of bacterium or This impairment manifests itself in This article briefly reviews the several ways. For example, alcoholics main features and components of the GYONGYI SZABO, M.D., PH.D., is a are prone to infections by various immune system and summarizes some research associate professor of medi- disease-causing microorganisms (i.e., of the consequences and mechanisms cine in the Department of Medicine, pathogens); have a decreased ability to of alcohol use on the body’s defense University of Massachusetts Medical fight these infections; and have an against pathogens. Center, Worcester, Massachusetts. 30 ALCOHOL HEALTH & RESEARCH WORLD Alcohol and Compromised Immunity virus that enters the body, whether it is cules that function cooperatively to nize and bind to antigens. Like T cells, the first or second infection by that mount a complex host defense and each B cell also recognizes only one organism. Acquired immunity, in thereby amplify and focus the protection specific antigen and becomes activated contrast, is activated only after the offered by the innate immunity. The when it comes into contact with it. body is exposed to a pathogen for the most important cells involved in ac- Most activated B cells develop into so- first time. In addition, the acquired quired immunity are T lymphocytes, or called plasma cells, which secrete their response is specific to one particular T cells, and B lymphocytes, or B cells. antibodies into the blood or lymph. pathogen. For example, when Myco- These cells circulate in the blood or There the antibodies can bind to their bacterium tuberculosis, the bacterium reside in special lymphoid tissues (e.g., target antigens (e.g., a virus or a virus- that causes tuberculosis, enters the the spleen, lymph nodes, and tonsils), infected cell) and thus mark them for body, the contact with that pathogen where they can encounter antigens and destruction. Other B cells become activates cells involved in acquired initiate an immune response. memory cells, which help the body immunity. These activated cells attack T cells and B cells are the corner- fight a second infection by the same only M. tuberculosis and no other stones of two types of immune re- pathogen more expeditiously. bacteria or viruses. The activated cells sponses, the cell-mediated immunity The T-cell and B-cell responses are also generate a kind of immune “mem- and the antibody-mediated (i.e., hu- not independent of each other, however, ory” that allows the body to fight a moral) immunity. The cell-mediated but are intricately intertwined. Thus, B second infection by the same pathogen immunity relies primarily on T cells cells that have bound an antigen serve even faster and more efficiently. that are activated by exposure to anti- as antigen-presenting cells that can The elements of innate immunity gen-presenting cells (e.g., monocytes, activate a T-cell response. Moreover, B include white blood cells that ingest and macrophages, and B cells). Each anti- cells and T cells communicate with each destroy microorganisms (i.e., phago- gen-presenting cell displays only one other and with other immune cells by cytes); certain proteins that circulate in antigen (e.g., a viral protein) on its secreting numerous cytokines that can the blood, called the complement1 surface and thus stimulates only T influence various components of both system; and signaling molecules (i.e., cells that recognize this specific anti- the nonspecific and specific immune cytokines) that are produced and secret- gen. The activated T cell then can responses. For example, some T cells ed by some of the phagocytes. Several bind to other cells carrying the same produce cytokines that stimulate their different types of phagocytes exist, with antigen (e.g., virus-infected cells) and own activity or that of other T cells. specific functions as follows: initiate their destruction. Several sub- Other subgroups of T cells secrete cy- populations of T cells have specific • Neutrophils ingest and thereby de- tokines that inhibit the cell-mediated functions in the complex chain of and humoral immunity and thus prevent stroy pathogens, primarily invading events occurring during an immune bacteria. an excessive reaction of the immune response: system. Finally, some T-cell–derived • Monocytes that circulate in the • Helper T cells produce and secrete cytokines enhance B-cell multiplication, blood or that have entered the cytokines that stimulate the activity differentiation, and antibody production. tissues (i.e., macrophages) ingest of other immune cells. The largest family of cytokines are the and destroy a variety of foreign interleukins (IL’s), which are produced substances and microorganisms. • Cytotoxic T cells recognize anti- in various cell types and have numerous Monocytes also exhibit pathogen- gens on the surface of virus-infect- functions (see table). derived proteins and other mole- ed or transplanted cells and destroy The following example may help cules (i.e., antigens) on their surfaces these cells. illustrate some of the complex interac- in order to activate other cells in • Suppressor T cells inhibit other tions that take place during an immune the immune system. Finally, mono- immune responses, thereby pre- response. When a person sustains a cytes and macrophages secrete venting overreaction of the im- small injury, such as a cut, bacteria can cytokines that help regulate im- mune system. enter the body and the bloodstream mune system activity. through the wound. Phagocytes (e.g., • Delayed-type hypersensitivity T • Natural killer (NK) cells recognize monocytes and neutrophils) patrolling cells produce cytokines that induce the blood encounter some of these and eliminate cells in the body that a localized inflammatory response bacteria; identify them as foreign to have been infected by parasites or and attract macrophages and cyto- the body; and engulf, ingest, and de- that have turned into cancer cells. toxic T cells to that site to elimi- stroy them. During the intracellular nate the antigen. The elements of acquired immunity breakdown of the ingested bacteria, include numerous cell types and mole- The B cells produce the humoral the phagocytes generate small proteins immunity. These cells carry immune or protein fragments that serve as 1For a definition of this and other technical terms used throughout this article, see the proteins (i.e., antibodies, or immuno- antigens. The phagocytes display these central glossary, pp. 93–96. globulins) on their surface that recog- antigens on their cell surface, together VOL. 21, NO. 1, 1997 31 Important Cytokines of the Immune System Cytokine Primary Source Principal Functions Inflammatory cytokines Interferon alpha (IFN-α) Macrophages