Immune Response

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).