Studied in this branch are the immune responses in organisms. How toxins are produced? How the antigens influence the formation of antibodies? How protective vaccination helps in combating the diseases? How immune system collapses (as in AIDS) are some of the questions for which immunology as a branch of microbiology is trying to find out answers.
Immunology is a branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ and in vivo. Immunology has applications in several disciplines of science, and as such is further divided.
Even before the concept of immunity (from immunis, Latin for "exempt") was developed, numerous early physicians characterized organs that would later prove to be part of the immune system. The key primary lymphoid organs of the immune system are the thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skinand liver. When health conditions warrant, immune system organs including the thymus, spleen, portions of bone marrow, lymph nodes and secondary lymphatic tissues can be surgically excised for examination while patients are still alive.
The immune system, which is made up of special cells, proteins, tissues, and organs, defends people against germs and microorganisms every day. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and infection.
About the Immune System
The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade body systems and cause disease.
The immune system is made up of a network of cells, tissues, and organs that work together to protect the body. The cells involved are white blood cells, or leukocytes, which come in two basic types that combine to seek out and destroy disease-causing organisms or substances.
Leukocytes are produced or stored in many locations in the body, including the thymus, spleen, and bone marrow. For this reason, they're called the lymphoid organs. There are also clumps of lymphoid tissue throughout the body, primarily as lymph nodes, that house the leukocytes.
The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.
The two basic types of leukocytes are:
1. phagocytes, cells that chew up invading organisms
2. lymphocytes, cells that allow the body to remember and recognize previous invaders and help the body destroy them
A number of different cells are considered phagocytes. The most common type is the neutrophil, which primarily fights bacteria. If doctors are worried about a bacterial infection, they might order a blood test to see if a patient has an increased number of neutrophils triggered by the infection. Other types of phagocytes have their own jobs to make sure that the body responds appropriately to a specific type of invader.
The two kinds of lymphocytes are B lymphocytes and T lymphocytes. Lymphocytes start out in the bone marrow and either stay there and mature into B cells, or they leave for the thymus gland, where they mature into T cells. B lymphocytes and T lymphocytes have separate functions: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has identified.
Here's how it works:
When antigens (foreign substances that invade the body) are detected, several types of cells work together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that lock onto specific antigens.
Once produced, these antibodies continue to exist in a person's body, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. So if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again.
This is also how immunizations prevent certain diseases. An immunization introduces the body to an antigen in a way that doesn't make someone sick, but does allow the body to produce antibodies that will then protect the person from future attack by the germ or substance that produces that particular disease.
Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That's the job of the T cells, which are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed. (Some T cells are actually called "killer cells.") T cells also are involved in helping signal other cells (like phagocytes) to do their jobs.
Antibodies also can neutralize toxins (poisonous or damaging substances) produced by different organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.
All of these specialized cells and parts of the immune system offer the body protection against disease. This protection is called immunity.
Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory.
The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into a more primitive innate immune system and, in vertebrates, an acquired or adaptive immune system. The latter is further divided into humoral (orantibody) and cell-mediated components.
The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are specific proteins released from a certain class of immune cells known as B lymphocytes, while antigens are defined as anything that elicits the generation of antibodies ("anti"body "gen"erators). Immunology rests on an understanding of the properties of these two biological entities and the cellular response to both.
Immunological research continues to become more specialized, pursuing non-classical models of immunity and functions of cells, organs and systems not previously associated with the immune system.
Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features.
The diseases caused by disorders of the immune system fall into two broad categories:
The most well-known disease that affects the immune system itself is AIDS, an immunodeficiency characterized by the suppression of CD4 ("helper") T cells, dendritic cells andmacrophages by the Human Immunodeficiency Virus (HIV).
The body’s capability to react to antigen depends on a person's age, antigen type, maternal factors and the area where the antigen is presented. Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like Staphylococcus and Pseudomonas. In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns.
This is due to lower opsonic activity, as well as diminished upregulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborn's phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early during gestation but are not fully active.
Maternal factors also play a role in the body’s immune response. At birth, most of the immunoglobulin present is maternal IgG. Because IgM, IgD, IgE and IgA don’t cross the placenta, they are almost undetectable at birth. Some IgA is provided by breast milk. These passively-acquired antibodies can protect the newborn for up to 18 months, but their response is usually short-lived and of low affinity. These antibodies can also produce a negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the antigen itself then the child will produce a dampened response.
Passively acquired maternal antibodies can suppress the antibody response to active immunization. Similarly the response of T-cells to vaccination differs in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these same responses in neonates. Between six to nine months after birth, a child’s immune system begins to respond more strongly to glycoproteins, but there is usually no marked improvement in their response to polysaccharides until they are at least one year old. This can be the reason for distinct time frames found in vaccination schedules.
During adolescence, the human body undergoes various physical, physiological and immunological changes triggered and mediated by hormones, of which the most significant in females is 17-β-oestradiol (an oestrogen) and, in males, is testosterone. Oestradiol usually begins to act around the age of 10 and testosterone some months later. There is evidence that these steroids act directly not only on the primary and secondary sexual characteristics but also have an effect on the development and regulation of the immune system, including an increased risk in developing pubescent and post-pubescent autoimmunity. There is also some evidence that cell surface receptors on B cells and macrophages may detect sex hormones in the system.
The use of immune system components to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used in the context of the treatment of cancers together with chemotherapy (drugs) and radiotherapy (radiation). However, immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies or autoimmune diseases.
Immunotherapy (also called biologic therapy or biotherapy) is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function. Although it is not entirely clear how immunotherapy treats cancer, it may work by stopping or slowing the growth of cancer cells, stopping cancer from spreading to other parts of the body, or helping the immune system increase its effectiveness at eliminating cancer cells.
There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies, and cancer vaccines.
When the body’s immune system detects antigens (harmful substances, such as bacteria, viruses, fungi, or parasites), it produces antibodies (proteins that fight infection). Monoclonal antibodies are made in a laboratory, and when they are given to patients, they act like the antibodies the body produces naturally. Monoclonal antibodies are given intravenously (through a vein) and work by targeting specific proteins on the surface of cancer cells or cells that support the growth of cancer cells. When monoclonal antibodies attach to a cancer cell, they may accomplish the following goals:
Allow the immune system to destroy the cancer cell. The immune system doesn't always recognize cancer cells as being harmful. To make it easier for the immune system to find and destroy cancer cells, a monoclonal antibody can mark or tag them by attaching to specific parts of cancer cells that are not found on healthy cells.
Prevent cancer cells from growing rapidly. Chemicals in the body called growth factors attach to receptors on the surface of cells and send signals that tell the cells to grow. Some cancer cells make extra copies of the growth factor receptor, which makes the cancer cells grow faster than normal cells. Monoclonal antibodies can block these receptors and prevent the growth signal from getting through.
Deliver radiation directly to cancer cells. This treatment, called radioimmunotherapy, uses monoclonal antibodies to deliver radiation directly to cancer cells. By attaching radioactive molecules to monoclonal antibodies in a laboratory, they can deliver low doses of radiation specifically to the tumor while leaving healthy cells alone. Examples of these radioactive molecules include ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar).
Diagnose cancer. Monoclonal antibodies carrying radioactive particles may also help diagnose certain cancers, such as colorectal, ovarian, and prostate cancers. Special cameras identify the cancer by showing where the radioactive particles accumulate in the body. In addition, a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) may use monoclonal antibodies to determine the type of cancer a patient may have after tissue has been removed during a biopsy.
Carry powerful drugs directly to cancer cells. Some monoclonal antibodies carry other cancer drugs directly to cancer cells. Once the monoclonal antibody attaches to the cancer cell, the cancer treatment it is carrying enters the cell, causing the cancer cell to die without damaging other healthy cells. Brentuximab vedotin (Adcetris), a treatment for certain types of Hodgkin and non-Hodgkin lymphoma, is one example
Other monoclonal antibodies approved by the U.S. Food and Drug Administration (FDA) to treat cancer include:
· Alemtuzumab (Campath)
· Bevacizumab (Avastin)
· Cetuximab (Erbitux)
· Ipilimumab (Yervoy)
· Ofatumumab (Arzerra)
· Panitumumab (Vectibix)
· Rituximab (Rituxan)
· Trastuzumab (Herceptin).
Clinical trials of monoclonal antibodies are ongoing for several types of cancers.
Side effects of monoclonal antibody treatment are usually mild and are often similar to an allergic reaction. Possible side effects include rashes, low blood pressure, and flu-like symptoms, such as fever, chills, headache, weakness, extreme tiredness, loss of appetite, upset stomach, or vomiting.
Although monoclonal antibodies are considered a type of immunotherapy, they are also classified as a type of targeted treatment (a treatment that specifically targets faulty genes or proteins that contribute to cancer growth and development).
Like monoclonal antibodies, non-specific immunotherapies also help the immune system destroy cancer cells. Most non-specific immunotherapies are given after or at the same time as another cancer treatment, such as chemotherapy or radiation therapy. However, some non-specific immunotherapies are given as the main cancer treatment.
Two common non-specific immunotherapies are:
Interferons. Interferons help the immune system fight cancer and may slow the growth of cancer cells. An interferon made in a laboratory, called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]), is the most common type of interferon used in cancer treatment. Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair.
Interleukins. Interleukins help the immune system produce cells that destroy cancer. An interleukin made in a laboratory, called interleukin-2, IL-2, or aldesleukin (Proleukin), is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, which can be treated with other medications. Some people may also experience flu-like symptoms.
A vaccine is another method used to help the body fight disease. A vaccine exposes the immune system to a protein (antigen) that triggers the immune system to recognize and destroy that protein or related materials. There are two types of cancer vaccines: prevention vaccines and treatment vaccines.
Prevention vaccine. A prevention vaccine is given to a person with no symptoms of cancer to prevent the development of a specific type of cancer or another cancer-related disease. For example, Gardasil is a vaccine that prevents a person from being infected with the human papillomavirus (HPV), a virus known to cause cervical cancer and some other types of cancer. It was the first FDA-approved vaccine for cancer. Cervarix is another vaccine that is approved to prevent cervical cancer in girls and women.
Treatment vaccine. A treatment vaccine helps the body's immune system fight cancer by training it to recognize and destroy cancer cells. It may prevent cancer from coming back, eliminate any remaining cancer cells after other types of treatment, or stop cancer cell growth. A treatment vaccine is designed to be specific, which means it should target the cancerous cells without affecting healthy cells. At this time, sipuleucel-T (Provenge) is the only treatment vaccine approved in the United States. It is designed for treating metastatic prostate cancer. Additional cancer treatment vaccines are still in development and only available through clinical trials.
The study of the interaction of the immune system with cancer cells can lead to diagnostic tests and therapies with which to find and fight cancer.
Reproductive immunology refers to a field of medicine that studies interactions (or the absence of them) between the immune system and components related to there productive system, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier.
The concept has been used by fertility clinics to explain the fertility problems, recurrent miscarriages and pregnancy complications observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is the new up and coming method for treating many cases of previously "unexplained infertility" or recurrent miscarriage.
Immunology is strongly experimental in everyday practice but is also characterized by an ongoing theoretical attitude. Many theories have been suggested in immunology from the end of the nineteenth century up to the present time. The end of the 19th century and the beginning of the 20th century saw a battle between "cellular" and "humoral" theories of immunity. According to the cellular theory of immunity, represented in particular by Elie Metchnikoff, it was cells – more precisely, phagocytes – that were responsible for immune responses. In contrast, the humoral theory of immunity, held, among others, by Robert Koch and Emil von Behring, stated that the active immune agents were soluble components (molecules) found in the organism’s “humors” rather than its cells.
In the mid-1950s, Frank Burnet, inspired by a suggestion made by Niels Jerne, formulated the clonal selection theory (CST) of immunity. On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (pathogens, an allograft) trigger a destructive immune response. The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells. The self/nonself theory of immunity and the self/nonself vocabulary have been criticized, but remain very influential.
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