Introduction
The study of immunology began during the mid-20th century after doctors and researchers began to comprehend the means through which the adaptive immune system helps the body to fight disease causing organisms (1). According to Janeway et al. (2), the foundation of immunology can be attributed to Edward Jenner’s development of the smallpox vaccine in 1796 and Louis Pasteur discovery of microbes in 1859. Over the years, immunotherapy has evolved to become one of the most effective means of curing and managing various diseases that could otherwise be fatal.
Immunotherapy
Immunotherapy describes a method of medical treatment that enhances, induces or suppresses the immune system to cure diseases (2). Immunotherapy uses the body’s own immune system to target specific pathogens that would otherwise have overwhelmed the body. In 1796, Jenner discovered that the introduction of the cow pox virus into a human host not only caused mild disease but also caused a subsequent immunity to small pox (2). This marked the beginning of biotherapy and would be the foundation in which immunotherapy would begin. The discovery of microbes by Pasteur and the detailed characterization of bacteria and their infections by Robert Koch gave rise to the Germ Theory of disease (3). This discovery was the first step in immunology as studies on how the immune system works and the components on the immune system were extensive undertaken.
Breakthrough in immunology and its application took place when William Corey discovered that some cancer victims who had received minor infections during surgery displayed tumor regression (4). In 1891, Corey began introducing Streptococcus pyogenes organisms into tumors. He discovered that in some patients the tumors disappeared and recurrence was only after a very long time (3, 4). Corey thus became the first person to use immunology to treat diseases and has thus been dubbed by several scientists as “the father of immunology” (1-3-4).
Corey’s work generated a lot of debates and a new field of medicinal science was formed. Researchers undertook to understand the human immune system better in order to find cures and improve the immunology field. In order to understand immunology, it is important to understand the human immune system and how it works.
Immune System
The immune system is a system of substances, special cells and organs that protects organisms from infections through the recognition and subsequent elimination of pathogens and tumor cells (5). The immune system has evolved to be able to distinguish between disease causing pathogens and healthy tissues (self-non-self discrimination) (3). Most disease causing pathogens such as viruses, parasites and bacteria are usually made up of proteins and other substances not found in the human body. These foreign substances causes the generation of antibodies that raises the alarm activating the immune system (6).
The immune system uses a layered approach to protect people from diseases. The layered approach works with increasing specificity with the first layer being physical barriers such as the skin than stops pathogens from accessing the human body (2, 6). “The innate immune system provides an immediate response to purge out pathogens should the physical barriers be breached” (2-3-4). In case the innate system is unable to eliminate the pathogens, it activates the adaptive immune system. The adaptive immune system adapts its response to the pathogen to increase its ability to recognize the pathogen. After the pathogen is eradicated, the improved response is stored as an immunological memory allowing the immune system to respond better should the same pathogen infect the host again (5, 6).
Innate Immune System
The innate immune system can be described as that part of the immune system that destroys pathogens and other foreign organisms in a non-specific way (1-2-6). It recognizes and attacks disease causing organisms in a standard manner subsequently it does not offer protective or long-lasting immunity to the host. The cells of the innate immune system are mainly leucocytes (white blood cells) that are produced from the bone marrow (6). In the innate immune system these leukocyte cells include; mast cells and natural killer cells (2, 6). The innate immune system is also composed of phagocytic cells that include dendritic cells and macrophages among others (2, 6).
In the human body, the mast cells are usually concentrated in the mucous membrane. They are very crucial to the clotting process as they release heparin and histamine to prevent inflammation and initiate clotting (5). The natural killer (NK) cells play a very crucial part in the innate immune system. Although they do not participate in pathogen elimination, they partake in the elimination of worn out and abnormal cells (2-3-6-7-8).
The dendritic cells are responsible for recognizing antigens and then presenting them to the T-cells for elimination (6). They thus act as a bridge between the innate and adaptive systems. The macrophages are a very efficient group of phagocytes that destroys pathogens by binding with them and then engulfing them (2-3-7).
Adaptive Immune System
The response of the adaptive immune system is specific according to the type of antigen produced. It is triggered by the antigen presentation process that is carried out by dendritic cells (5). The adaptive immune system response is adapted to specific pathogens and it evolves over time making them better suited to respond should the pathogen attack again (2, 5). The adaptive immune system (lymphocytes) consists of, killer T-cells, Helper T-cells, gamma/delta T-cells and B-cells (3).
The B-cells are created in the bone marrow and usually reside in the lymph nodes. The B-cells do not attack diseased cells or pathogens directly rather they manufacture antibodies that identify and attach to a specific antigen (3, 5). The antibodies then destroy the infected cells or act as beacons alerting the T-cells on the position of the antigens.
One of the most important components of the immune system found in the blood stream is the T cells. The T-cells are equipped with special proteins in their cell membranes enabling them to detect and react to tumor cells, pathogens and infected cells (2, 5, 6). Killer T-cell attack all unwanted cells in the body (pathogens, worn out cells, tumor cells and infected cells). Once in contact with an unwanted cell, they release chemicals that destroy the unwanted cells (7). Helper T-Cells release chemicals in the body to enhance the fighting capability of both T-cells and B-cells. Finally, the suppressor T-cells ensures that healthy tissues and cells are not attacked by the other components of the immune system (7, 8).
Active and Passive Immunotherapy
“There are mainly two types of immunotherapy: active immunotherapy and passive immunotherapy” (1-2-3-4-5). Active immunotherapy mainly involves the stimulation and enhancement of the immune system to fight a particular disease (7-9). Passive immunotherapy on the other hand involves the use of manufactured immune system compounds i.e. antibodies to fight a disease (7-9). These manufactured antibodies do not rely on the natural response of the immune system but are programmed to attack the infection or cancer cells (9). Active immunotherapy is used in mainly two ways. The first method involves the use of T-cell therapy to cure diseases. This involves the extraction of T-cells from the patient, putting them in a suitable environment, multiplying the cells in massive quantities and then introducing them back to the human host (3-4-7). T-cell therapy is particularly effective in treating viral diseases and managing cancer (3, 4). The second method of active immunotherapy is by using vaccine to fight a targeted infection. Vaccines are compounds, chemicals or organic material created in the blood that help the body generate antibodies that will trigger an immune response (2, 3).
Passive immunotherapy involves the use of manufactured compounds aimed at fighting a disease (2-3-4). The main form of passive immunotherapy involves the use of antibodies to deliver therapeutic treatments to infected cells and tumor cells. This technique involves extracting specific antibodies that correspond to a particular disease, infusing them with therapeutic agents and then injecting them into the host (3, 4). These antibodies directly attack the infected tissue or cancer cells thus sparing healthy tissues. Therapeutic agents may include radioactive substances to treat cancer or other treatment for certain diseases (4, 7). Another form of passive immunotherapy is through the use of genetically engineered T-Cells (1, 7). This is carried out by infecting the host’s cells with a virus that has been genetically modified to store a copy of a T cell receptor (TCR) gene meant to identify a particular pathogen or tumor cells. The virus is engineered so that it cannot reproduce and upon its death, the TCR gene remains in the host’s T-cells (4). The modified T-cells are injected into the patient after which the directly target the virus they have been reprogrammed to identify.
Applications of Immunotherapy
Immunotherapy can be used in a variety of cases. It can either be used to stimulate the body defenses to attack an illness or it can be used to suppress immune responses in case of auto immune disorders. Advancement in science has greatly improved the manner in which immunotherapy is applied and the development of genetic engineering has created enormous potential for this field of medical science.
Immunotherapy in the Treatment of Cancer
While cancer occurs to people with compromised immune system, it is also common to find cancer developing in healthy people. Tumor cells are usually defective cells common in the host and thus may not be readily identifiable by the immune system. Cancer immunotherapy involves the enhancement and stimulation of the host immune system so that it can be able to detect and attack the cancerous cells (3, 4).
Cancer immunotherapy mainly works based on T cell activation and antigen presentation. Cancer immunotherapy mainly takes place in two ways. The first method is active immunotherapy that entails training the host’s immune system to identify the tumor cells as damaged materials that should be eliminated (3, 4). The second method is a form of passive immunotherapy whereby therapeutic antibodies are administered to the patient in form of drugs (3-4-11). The therapeutic antibodies are genetically engineered and after administration, they produce compounds that activate the host’s own immune system to fight the tumor cells.
One popular method for cancer immunology involves T-cell based cancer immunology. Understanding the interaction between T cells and MHC has enabled scientist to develop a passive immunotherapy referred to as monoclonal antibody therapy (mAb). In this treatment, the T-cells are programmed to attack specific antigens of the tumor or other protein characteristics of the cancer cells (11). The injected T-cells bind with the target tumor cells and release toxins that have been genetically engineered in the lab to kill them off.
Another method of cancer immunotherapy is through the use of active immunotherapy whereby patients are injected with cancer vaccines in order to activate an immune response to fight the tumor cells (3, 4). The vaccines are made by injecting the patient with inactivated cancer cells. The inactivated cancer cells acts as antigens thus activating the immune system not only to attack them but also to attack the existing tumor cells in the host (3, 4, 12).
Immunotherapy in Allogeneic Transplantations
Allogeneic transplantation involves grafting body tissue from one person to another. Once transplantation of the tissue is done, the host’s immune system identifies the grafted tissue as a foreign substance (antigen) and seeks to destroy it by releasing antibodies (13). The antibodies start attacking the grafted tissue thereby inhibiting cell metabolism leading to the eventual death of the transplanted tissue (13, 14).
In order to prevent this from occurring, it is usually necessary to control the host’s immune response. This is usually carried out through the use of tolerance induction or immunosuppressive therapy (2, 13). Immunotherapy in transplantation is important as it only suppresses immune response against the grafted tissue while leaving the rest of the immune system fully intact (14). Immunotherapy in transplantations also helps in curbing infections that may arise after the surgery.
The main agents used in immunosuppressive therapy mainly interfere with the activation processes of both T cells and B cells (14). In allogeneic transplantations, immunotherapy includes the use of corticosteroids, polyclonal antibodies, TOR inhibitors and mAbs (13). Corticosteroids have been used to interfere with immune system response. Corticosteroids usually interfere with the concentration of white blood cells in the area where they are introduced. The corticosteroids cause a redistribution of the leucocytes to other lymph nodes in the body away from the point of introduction (15). This interference usually lasts between 24 to 48 hours. The corticosteroids also cause a reduction in macrophages and dendrite counts which are important for antigen presentation and inflammation. Once injected into the grafted tissue, the corticosteroids causes a redistribution of the T cells preventing graft rejection and also reduces the number of macrophages preventing inflammation (15).
The second important immunotherapeutic method to prevent graft rejection is through the use of Monoclonal antibodies (mAb). Monoclonal antibodies are antibodies that are very antigen specific (13). They are genetically engineered by first immunizing mice with a specific antigen. The B-cells taken from the spleens of the mice are then fused with myeloma cells from the mice. This result in a hybridoma that can provide numerous antibodies that will specifically attack that antigen (16). In the case of immunosuppressive therapy, the antigen introduced are activated T-cells that are targeting the graft. The mAbs are injected into the host so that they can attack T-cells activated to fight the graft.
Conclusion
Immunotherapy has advanced a lot since its early discovery in the mid-19th century. In the modern age, immunotherapy offers a means to treat cancer without the serious side effects common with other treatment method. Immunotherapy uses the body’s own immune system to operate and as such has very little side effects. Although research has shown that immunotherapy is not necessarily better than other treatment method, it still forms a crucial part in treating cancer and other incurable diseases as well as preventing graft rejection.
Immunotherapy subsists as either inert immunotherapy or dynamic immunotherapy. Active immunotherapy involves introduction of compounds into the human body in order to enhance or activate an immune response. Passive immunotherapy on the other hand involves the modification of the host own cells so that they can effectively eliminate antigens in the body.
With the continual development of genetic engineering, it is possible that immunotherapy will become one of the main means of treating cancer and other diseases. Each day, scientists learn more and more about the immune system. New antigens are being discovered and better ways of genetic modifications are being developed. It is thus quite possible that along the way, immunotherapy may provide the answer to the cancer menace and other autoimmune diseases.
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