The+Immune+System+and+Cancer

=**The Immune System and Cancer**= Tiffany Grayson 5/20/2010

Cancer can be defined as abnormal cell growth caused by damaged DNA. Cancer can involve any tissue or organ in the body and can be classified as carcinoma, sarcoma, myeloma, leukemia, or lymphoma. Among the most common are skin, breast, and prostate cancers. The root of a growing cancer is caused by damaged/mutated DNA in a cell. The damaged DNA in the cell does not allow the cell to repair itself. The cell's transformed DNA changes its genes for cell division, and this leads to high rates of reproduction. This uncontrollable growth then proliferates into a tumor, a mass of tissue which continues to grow and spread, interrupting the normal functions of the body. Tumors can also release harmful hormones. Cancerous cells that are shed by the tumor use the blood and lymph systems as transportation throughout the body.

How does the immune system play a role in the development of cancerous cells?

One scientific explanation for immune system's response to cancer is the **Immune Surveillance Concept** (Tortora, G., Funke, B., Case, L., 2010) which states that:
 * cancer cells appear in the body frequently
 * the immune system developed in order to eliminate these cells
 * appearance of cancerous growth represented failure of the immune system

What supports this concept?
-As we age, so does the strength and capacities of our immune system. -Cancer most commonly affects older adults -results from a natural or artificial (such as immunosuppressent drugs used in organ transplants to inhibit the immune system and thus avoids destruction of the transplant) cause (Tortora, G., Funke, B., Case, L., 2010).
 * Old age
 * I//mmunosuppression//: reduced efficiency of the immune system

Causes of Cancer:

 * //DNA damage/mutations:// Changes in DNA that affect the cell's replication rate and malignant properties. DNA damage can be a result of the following:
 * //Genes-inheritance:// Inheritance of an oncogene which contributes to normal cells becoming cancerous cells.
 * //Carcinogens:// Substance s that damage cell DNA, such as tobacco, asbestos, radiation such as gamma and x-rays, the sun, and some elements of car exhaust. When the body is exposed to carcinogens, free radicals are formed that can take away electrons from other molecules in the body. This in turn damages cells and their normal properties/functions. (//"What is cancer?"//)
 * //Oncogenic Viruses//: A virus that can cause tumors. 10% of cancers are caused by a virus. Their genetic material alters the host cell's DNA. The virus replicates along with the host cell and causes changes to the host cell's characteristics. (Tortora, G., Funke, B., Case, L., 2010).



Mechanisms of the Body's Immune Response to Cancer:
Cancerous cells display antigens that are recognized by cells of the immune system called lymphocytes and put under attack by the immune system's humoral and cellular immune responses.


 * **The Humoral Immune Response** (B-cells, cytokines, and antibodies, innate immunity, non-specific):
 * 1) //Activation stage//: Invading cells are phagociti zed by an //antigen-presenting cell (APC)//, such as a macrophage. The invading cell is digested so it's antigens can be processed. Then the antigens are displayed on the surface of the APC along with the MHC Class II complex (Major Histocompatability Complex: a large gene family found in most vertebrates which contributes significantly to the immune system by encoding proteins that display self and nonself antigens). The antigen-MHC complex is recognized by an immune cell known as CD4+ or //helper T cell//. The helper T cell attacks by binding its antigen receptor to the displayed antigen. Another function of the helper T cell is the release cytokines (chemical messengers). The cytokines cause the helper T cells to multiply and encourages chemical communication between cells of the immune system, such as the cytokine interleukin-2 (IL-2), which stimulates the spreading of lymphocytes. The APC also releases a cytokine called TNF or Tumor Necrosis Factor which acts to trigger lysis in tumor cells. The helper T cells signal B cells (another class of lymphocytes) which recognize the antigen and multiply into antibody-producing cells.
 * 2) //Effector Stage//: B cells transform into plasma cells and secrete antibodies. The binding of the antibody to the antigens allows killer cells to more efficiently destroy the invading cells by way of phagocytosis and lysis. This binding also activates a complement—a group of proteins that puncture holes in the cell walls of the invading cells. (Cancer Research Institute)
 * **The Cellular (Cell-Mediated) Immune Response** (lymphocytes: T and B cells, adaptive immunity, highly specific antigen recognition):
 * //Activation Stage//: The antigen-presenting cell or APC host cell engulfs an invading virus by phagocytosis. Within the APC, a lysosome containing digestive enzymes combines with the phagosome (a vacuole surrounded particle absorbed by phagocytosis, in this case, the virus) to process the antigens. The processed antigens combine with MHC class II proteins and are displayed on the surface of the APC. A helper T cell recognizes that antigen and binds to the MHC class II protein-antigen complex, releasing chemical messengers such as the cytokine IL-2 (stimulates Cytotoxic T cells to proliferate) and gamma interferon (IFN-g; increases the APC's ability to display antigens, disables the replication of viral DNA or RNA, and rids the host cell of a pathogen). //("Human Interferon Gamma (IFN-G)//", 2000)
 * //Effector Stage:// The cytotoxic T cells (CD8+) recognize the MHC antigens on infected host cells and summon other killer T cells to the site of infection. Cytotoxic T cells bind to the MHC antigens on infected host cell. Once bound, the cytotoxic T cell to releases a powerful chemical called perforin, which causes lysis of infected cells. Regulatory T cells will inactivate cytotoxic T cells, B cells, helper T cells, and killer T cells when no longer needed. Memory T cells are left to quickly recognize and combat the same infection if it arises again. (Cancer Research Institute)



Unfortunately, the immune system doesn't always recognize cancerous cells.

Medical Prevention and Treatment of Cancer

 * **Chemotherapy**: Chemotherapy uses chemicals to treat cancerous growth by targeting cell division or DNA synthesis, sometimes in combination with radiation. Chemotherapy is designed to destroy rapidly dividing cancer cells, but since it does not target them alone, it also destroys healthy cells that divide rapidly (those in hair, bone marrow, and the digestive tract. Chemotherapy causes myelosuppression or a decreased production of red blood cells, decreased immune function, hair loss, and inflammation of the digestive tract lining. Usually it is delivered to a patient intravenously. It is considered a //systemic treatment//: which eliminates cancerous cells in great distances from the main site of cancer growth. (//"Treating Cancer With Chemotherapy//.")
 * **Monoclonal Antibody Therapy**: A recent form of cancer therapy drug involving monoclonal antibodies (mAb). These scientifically engineered molecules mimic immune cells and can bind to specific molecules. They attach to proteins on cancerous cells and are capable of delivering radiation in the form of radioactive particles, as well as anti-cancer drugs to cancerous cells. They also function to prevent tumor growth by blocking specific cell receptors. (//"Monoclonal Antibody Drugs"//, 2009.)


 * **Immunotherapy**: William B. Coley discovered that he could control the growth of some cancers with injections of a mixed vaccine containing streptococcal and staphylococcal bacteria (known as Coley's Toxins or the Coley Vaccine). (McCarthy E, 2006). This marked the beginning of a disease and cancer treatment that worked to suppress or enhance the body's immune response called immunotherapy. William B. Coley's discovery eventually led to the discovery of the Tumor Necrosis Factor (TNF), a cytokine produced by macrophages. It is capable of inducing apoptosis (programmed cell death), preventing viral replication, and destroying cancer cells. (Goodsell, D., 2005.). It is a major component of some immunotherapies. Many of the other substances used in immunotherapy are often derived from the cell components of bacterial microogranisms. These treatments are delivered to the body via injection. Immunotherapy can have side effects such as allergic reactions that range from mild local reactions (pain, swelling, redness) to more serious systemic reactions (hives, tightness in the chest, and swelling of the throat) that usually occur within minutes after treatment.
 * **Vaccines:** Vaccination against a specific virus that causes cancer can prevent the associated cancer. Such vaccines are known as preventative or prophylactic vaccines, and they are used to protect healthy individuals from developing cancer. Treatment or therapeutic vaccines is still an experimental form of treatment, and are intended to treat individuals with existing cancers by targeting and strengthening the immune system. ("//Cancer Vaccines//", 2009.)
 * **Immunotoxins**: Immunotoxins are proteins consisting of an antibody fragment linked to a toxin. It can bind to cancerous cells by binding to its surface antigens. It enters the cells by endocytocis (the cancerous cell's membrane engulfs the immunotoxin) and inactivates the cells ability to synthesize proteins, which leads to cell death. Immunotoxins are made from bacterial and plant toxins. For treatment, they are delivered into the bloodstream. (Pastan, Hassan, FitzGerald, and Kreitman, 2007.)
 * **Modified Viruses**: Researchers have recently found that viruses can be modified to recognize/kill tumor cells and replicate without harming healthy tissues. Adenovirus is a DNA virus used in cancer therapy. ("//Virus Tamed//", 2009).

Citations:
Cancer Research Institute. (n.d.). //Cancer and The Immune System, Humoral and Cellular Responses//. Retrieved from: http://www.cancerresearch.org/Resources.aspx?id=586

Davidson College. (2000). //Human Interferon Gamma (IFN-G)//. Retrieved from: http://www.bio.davidson.edu/courses/immunology/Students/spring2000/allred/protein.html

Goodsell, D. (2005). //The Molecular Perspective: Tumor Necrosis Factor//. Retrieved from: http://theoncologist.alphamedpress.org/cgi/content/full/11/1/83

Hopkins, J. (April 3, 2009). //Image of Cancer Dividing Cell// used and retrieved from: http://www.constant-tsai.com/?p=188

Lawrence Berkley Lab. (n.d.). //Image of a T-lymphocyte// used and retrieved from: http://www.daviddarling.info/encyclopedia/T/T-lymphocyte.html

McCarthy, E. (2006). //The Toxins of William B. Coley And The Treatment of Bone and Soft Tissue Sarcomas//. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888599/

Medical News Today. (n.d.) //What is Cancer? What Causes Cancer?.// Retrieved from: http://www.medicalnewstoday.com/info/cancer-oncology/whatiscancer.php

Mayo Clinic Staff. (2009). //Monoclonal Antibody Drugs for Cancer Treatment: How They Work//. Retrieved from: http://www.mayoclinic.com/health/monoclonal-antibody/ca00082

National Cancer Institute. (2009). //Cancer Vaccines.// Retrieved from: http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines#a5

Pastan, Hassan, FitzGerald, and Kreitman. (2007). //Immunotoxin Treatment of Cancer.// Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/17059365

Science Daily. (May 25, 2009). //Virus Tamed to Destroy Cancer Cells But Leave Healthy Cells Unharmed.// Retrieved from: http://www.medicalnewstoday.com/info/cancer-oncology/whatiscancer.php

Tortora, G., Funke, B., Case, L. (2010). //Microbiology, An Introduction, 10th Edition//. United States, Pearson.

//Treating Cancer With Chemotherapy//. (n.d.) Retrieved from: http://www.chemotherapy.com/treating_with_chemo/treating_with_chemo.jsp