Immune Response

Among the many threats organisms face are invasion and infection by bacteria, viruses, fungi, and other foreign or disease-causing agents. All organisms have nonspecific defenses (or innate defenses) that provide them with some of the protection they need. This type of defense exists throughout the animal kingdom, from sponges to mammals. Vertebrate animals, however, have an additional line of defense called specific immunity. Specific immunity is also called acquired immunity, adaptive immunity, or, most simply, an immune response.

Overview

One characteristic of specific immunity is recognition. Immune responses begin when the body recognizes the invader as foreign. This occurs because there are molecules on foreign cells that are different from molecules on the body's cells. Molecules that start immune responses are called antigens . The body does not usually start an immune response against its own antigens because cells that recognize self-antigens are deleted or inactivated. This concept is called self-tolerance and is a key characteristic that defines immune responses.

A second characteristic is specificity. Although all immune responses are similar, each time the body is invaded by a different antigen, the exact response is specific to that antigen. For example, infection with a virus that causes the common cold triggers a response by a different set of cells than infection with bacteria that causes strep throat.

A third characteristic is memory. After an antigen is cleared from the body, immunological memory allows an antigen to be recognized and removed more quickly if encountered again.

Antigen Presentation

Three groups of white blood cells are involved in starting an immune response. Although immune responses can occur anywhere in the body these cells are found, they primarily occur in the lymph nodes and spleen. These organs contain large numbers of antigen-presenting cells (APCs), T lymphocytes (or T cells ), and B lymphocytes (or B cells).

APCs include macrophages, dendritic cells, and B cells. These cells encounter the foreign invader and present the invader's antigens to a group of T cells called helper T cells (T_H cells). APCs do this by first engulfing an invader and bringing it inside the cell. The APC then breaks the invader apart into its antigens and moves these antigens to its cell surface.

Receptors are cell surface proteins that can attach to antigens. Each T_H cell has a different receptor, allowing each cell to recognize a different antigen. The APC "shows" the antigen to the T_H cells until there is a match between a T_H cell receptor and the antigen. The contact between the two cells stimulates the T_H cell to divide rapidly. This process is called clonal selection because only the T_H cells that recognize the foreign invader are selected to reproduce. Stimulated T_H cells also produce chemical messengers called cytokines. Cytokines are made by all immune cells and control the immune response.

Antigen Clearance

The large numbers of T_H cells activate two other populations of white blood cells: cytotoxic T cells (T_C cells) and B cells. Like T_H cells, each T_C cell and B cell has receptors that match one antigen. This is why the immune system can recognize millions of antigens with specificity. The cells with the appropriate receptor encounter the antigen, preparing them for activation. They receive the final signal necessary for clonal selection from T_H cells and cytokines.

Cloned T_C cells attach to invaders they recognize and release a variety of chemicals that destroy the foreign cell. Because this must happen through cell-to-cell contact, it is called cell-mediated immunity (or cellular immunity). It is especially effective at destroying abnormal body cells, such as cancerous cells or virus-infected cells.

Cloned B cells destroy foreign invaders differently. After activation by T_H cells, B cells release proteins called antibodies. Antibodies travel through the body's fluids and attach to antigens, targeting them for destruction by nonspecific defenses. This type of immune response is called antibody -mediated immunity (or humoral immunity). It is especially effective at destroying bacteria, extracellular viruses, and other antigens found in body fluids.

Immunologic Memory

A primary immune response happens the first time that the body encounters a specific antigen. It takes several days to begin and one or two weeks to reach maximum activity. A secondary immune response occurs if the body encounters the same antigen at a later time. It takes only hours to begin and may peak within a few days. The invader is usually removed before it has a chance to cause disease. This is because some of the cloned T_C cells and B cells produced during a primary immune response develop into memory cells. These cells immediately become activated if the antigen appears again. The complex interactions among cells described above are not necessary.

In fact, this is what happens when an individual is immunized against a disease. The vaccination (using weakened or killed pathogens ) causes a primary immune response (but not the disease) and the production of memory cells that will provide protection if exposed to the diseasecausing agent.

Immune System Disorders

Studying immune responses also allows scientists to understand immune system diseases. For example, hypersensitivity disorders occur when the immune system overreacts to an antigen, causing damage to healthy tissues. The result of this excessive antibody and T_C cell activity can be relatively harmless (as with allergies to pollen, poison ivy, or molds) or deadly (as with autoimmune diseases or allergies to bee venom and antibiotics).

At the opposite end of the spectrum are immunodeficiency diseases, conditions in which the body does not respond effectively against foreign invaders. HIV (human immunodeficiency virus) infection causes AIDS (acquired immunodeficiency syndrome) by attacking T_H cells. Occasionally an individual is born with a deficient immune system, but these disorders are usually acquired (for example, from radiation treatment, chemotherapy, or infection with HIV). Whatever the cause, the individual has a more difficult time fighting infections.

Because immune responses exhibit the characteristics of self-tolerance, specificity, and memory, a healthy body is well equipped to remove foreign invaders and prevent recurrent infections. Age, nutrition, exercise, and stress all affect the ability of the body to fight disease.

see also AIDS; Antibody; Autoimmune Disease; Nonspecific Defense

John M. Ripper

Bibliography

Beck, Gregory, and Gail S. Habicht. "Immunity and the Invertebrates." Scientific American 275, no. 5 (1996): 60–65.

Friedlander, Mark P., Jr., and Terry M. Phillips. The Immune System: Your Body's Disease-Fighting Army. Minneapolis, MN: Lerner Publications Company, 1998.

Gustav, J. V. "Life, Death, and the Immune System." Scientific American 269, no. 3 (1993): 53–62.

National Institutes of Health. Understanding the Immune System. Washington, DC: National Institutes of Health, 1993.

Paul, William. E. "Infectious Diseases and the Immune System." Scientific American 269, no. 3 (1993): 90–97.

Immune response

Definition

The ability of any given cell in the body to distinguish self from nonself is called the immune response.

All cells in the body are recognized as self. Any microorganism (for example, a foreign body or tumor) that invades or attacks the cells is recognized as nonself—or foreign—requiring the immune system to mount a combat against the nonself.

Immune system

The immune system is comprised of a network of immune cells that are generated in the bone marrow stem cell (a cell whose daughter cells may develop into other types of cells). From stem cells different types of immune cells originate that can handle specific immune functions. Phagocytes (cell eaters), serve as the first line of defense, engulfing dead cells, debris, virus, and bacteria. Macrophages are an important type of phagocyte, often presenting the antigen—which is usually a foreign protein—to other immune cells and thus are also called "antigen-presenting cells" (APC). T and B lymphocytes, important immune-system cells, are also capable of recognizing the antigen and become activated. T lymphocytes are classified into two subtypes: killer T cells (also called cytotoxic T cells) and helper T cells. Killer T cells recognize and kill the infected or cancer cells that contain the antigen or the foreign protein. Helper T cells release cytokines (chemical messengers) upon activation that either directly destroy the tumor or stimulate other cells to kill the target (tumor). B lymphocytes produce antibodies after recognizing the antigens. The antibodies, which help protect the body from the antigen, are normally specific to that particular antigen. In cases of tumor the specific antibodies attach to tumor cells and, through various mechanisms, impair the functions of the tumor, ultimately leading to the death of the cancer cell.

In addition to these lymphocytes are natural killer (NK) cells that particularly perform the task of eliminating foreign cells. Natural killer cells differ from killer T cells in that they target tumor cells and do not have to recognize an antigen before activation. These cells have been shown to be of potential use in treating cancer.

Immune system and cancer

The immune system serves as one of the primary defenses against cancer. When normal tissue becomes a tumor or cancerous tissue, new antigens develop on their surface. These antigens send a signal to immune cells such as the cytotoxic T lymphocytes, NK cells, and macrophages, which in turn directly kill the tumor cells or release substances like cytokines that may bring about tumor cell death. Thus, under normal circumstances, the immune system provides continued surveillance and eliminates cells that become cancers. However, tumors may survive by hiding or disguising their tumor antigens, or by producing substances that allow suppressor T cells (cells that block cytotoxic, or killer T cells that would normally attack the tumor) to proliferate (multiply).

Biological response modifiers in cancer therapy

Researchers have been working on stimulating the immune cells during cancer with substances broadly classified as biological response modifiers. Cytokines are one such substance. These are proteins that are predominantly released by immune cells upon activation or stimulation. During the 1990s the number of cytokines identified increased enormously and the functions associated with them are of immense potential in diagnostics and immune therapy. Some of the key cytokines that have proven therapeutic value in cancer are interleukin-2 (IL-2), Interferon gamma, and interleukin-12 (IL-12). Cytokines are normally injected directly to cancer patients; however, there are other cases where a cancer patient's own lymphocytes are modified under laboratory conditions and injected back into the patient. Examples of these are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TILs). These modified cells are capable of devouring cancer cells.

Immunoprevention of cancer

Immunotherapy is emerging as one of the management strategies for cancer. However, established tumors or large masses of tumor do not respond well to immunotherapy. There is clinical evidence, however, that suggests that patients with minimal residual cancer cells (a few cells left after other forms of cancer treatment) are potential candidates for effective immunotherapy. In these cases immunotherapy often results in a prolonged tumor-free survival. Thus, immune responses can be manipulated to prevent recurrence, even though it does not destroy large tumors. Based on results of immunotherapy trials, most immune therapies are geared towards designing immunoprotective strategies such as cancer vaccines .

Cancer vaccines

Cancer vaccines can be made either with whole, inactivated tumor cells, or with fragments or cell surface substances (called cell-surface antigens) present in the tumors. In addition to the whole cell or antigen vaccines, biological modifiers, like cytokines, serve as substances that boost immune response in cancer patients.

Since cancer vaccines are still under clinical evaluation, caution should be exercised while choosing them as the mode of therapy. The cancer care team will provide further insight on whether or not cancer vaccine or cytokine therapy will be beneficial after they assess the patient's stage and the various modes of treatments available.

Kausalya Santhanam, Ph.D.

Resources

BOOKS

DeVita, Vincent T., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. Philadelphia: J. B. Lippincott Company, 1997.

PERIODICALS

"Immunoprevention of Cancer: Is the Time Ripe?" Cancer Research (15 May 2000) 60: 2571-2575

"Therapies of the Future: Immunotherapy for Cancer." Scientific American (October 1996).

"Genetic Vaccines." Scientific American (July 1999).

OTHER

"Treating Cancer with Vaccine Therapy." National Cancer Institute. 2000. 5 July 2001 <http://cancertrials.nci.nih.gov/news/features/vaccine/html/page05.html>.

KEY TERMS

Antigen

—Molecules or fragments of molecules that belong to a foreign invader that can elicit an immune response. These may include germs, toxins, and tissues from another person used in organ transplantation.

Cytokines

—Proteins (chemical messengers) that are predominantly released by immune cells upon activation or stimulation that help bring about tumor cell death.

Stem cell

—A cell whose daughter cells may differentiate (develop into other cell types).

immune response The reaction of the body to foreign or potentially dangerous substances (antigens), particularly disease-producing microorganisms. The response involves the production by specialized white blood cells (B cells) of proteins known as antibodies, which react with the antigens to render them harmless (see immunoglobulin). The antibody–antigen reaction is highly specific. See also anaphylaxis; immunity.

im·mune re·sponse • n. the reaction of the cells and fluids of the body to the presence of a substance that is not recognized as a constituent of the body itself.