Immune system: The facts on
The human immune system does remarkable work. The cells of the immune system run through the body "on patrol" and distinguish "foreign" from "self". Antibodies can select pathogens such as bacteria, viruses or fungi. Specialized immune cells go into a highly complex interaction not only against each intruder. They also create a kind of memory: Thus, in further infection by bacteria already known to an immune response to start immediately.
In monitoring of tumor cells, the immune system faces a difficult task: This is the body's own cells. Your own body will not normally be attacked. Solve tumors in contrast to most organisms only rarely from inflammation. Thus lacking the immune system, the signal "foreign" or "bad" to start the immune response.
Has long been attempting to create this lack of response to cancer therapy and treatment of immunological methods - sometimes with amazing, but often with non-repeatable or transferable to any cancer patient outcomes. is "The" immunotherapy against cancer is not today. From the research, however, have revealed many insights that will benefit cancer patients in several ways.
Biological basis: How does the immune system?
The human immune system has adapted over millions of years in the defense against pathogens. Tumor cells, however, are not as foreign as bacteria, viruses or fungi: they wear in comparison to these invaders are still many features of the tissue from which they originate. Other mechanisms for the signal chain "sick cell - recognition and immune response - the death of the diseased cell" are important to be lost, however in many cancer cells: Cancer cells can "hide" by dropping the typical features of healthy cells. Or do they "fool" the immune system by accepting properties of other tissues. Also, signal plans, which are responsible for normal aging process of cells fail to, the cells are immortal.
The detection and destruction of cancer cells are the immune system is still possible. This process probably occurs in healthy very often without having some sense of it. The control of these processes is complex: an excessive reaction to the body's own cells could cause the immune system attacks not only tumor cells but also healthy tissue with similar properties and destroyed, a situation such as an initiator of the so-called autoimmune diseases such as rheumatoid arthritis or multiple sclerosis is suspected.
- Cancer researchers today are reluctant to speak of it, that the immune system "has failed" when cancer develops.
- Reliable tests that would prove such a failure in cancer patients, it is not.
- We now know also that there is not enough, the immune system non-specifically "to stimulate" to fight cancer. It is thought that this might even be dangerous.
With increasing knowledge of the body's defense mechanisms, more and more strategies are possible, specifically intervene in the biological mechanisms of tumor cell reduction. A replacement for surgery, radiotherapy, chemotherapy or hormone therapy provide immunotherapeutic methods but so far only in exceptional cases complement dar. Most immunotherapies other treatments only.
Biology of the immune system: How is an infection contained?
To protect against infection a functioning immune system is necessary for the pathogens and foreign substances recognized. This must address the immune system, four main tasks:
- Detection of infection
- Contain and if possible defense of the infection
- Immune Regulation: The immune system must be kept under control, so healthy, the body's own cells are not attacked.
- Protection against the recurrence of disease by an immunological memory
This runs the immune response in the right order, control various neurotransmitters, the immune system response. Interferons and interleukins are examples of such cytokines.
These mechanisms are sometimes also used when the immune system against the body's own cells or aged cells with a targeted defect.
Which components are part of the immune system?
The immune system is very complex. is a principal organ, it does not work, the defense needs throughout the body. The organs of the creation, development and maturation of immune cells include bone marrow and thymus. In the bone marrow caused the so-called stem cells. In addition, here refers to development and maturation of certain white blood cells instead of the B-cells or B lymphocytes (the "B" stands for bone marrow, English for bone marrow). In the thymus, mature and develop the various T-cells (the "T" stands for thymus). From their point of origin of the immune cells reach the blood and lymph vessels in all organs and tissues of the body.
Organs and tissues in which the immune cells are active, the spleen, all lymph nodes, throat and tonsils (tonsils) and lymphoid tissue on other mucous membranes, for example in the intestine.
Which cells requires an immune response?
The cells of the immune system arise from stem cells in the bone marrow. Since these stem cells arise from all other blood cell types, they are called "pluripotent".
From these stem cells develop into more stem cells, first with limited potential: the direct precursors of red blood cells (erythrocytes), platelets (thrombocytes) and the two major classes of white blood cells (leukocytes).
The red blood cells are responsible for transporting oxygen in the blood, the platelets for blood clotting. The various subgroups of leukocytes belong to the immune system.
* B-lymphocytes (plasma cells) produce antibodies against foreign or abnormal structures in the body, for example against pathogens. The long-lived memory B cells upon re-exposure to them with a known foreign body within hours an immune reaction triggered to prevent the outbreak of infection.
* T-lymphocytes (memory T cells, T helper cells, others) have different functions: to induce a specific immune response or the formation of cell-regulating hormones, called cytokines. Cytotoxic T cells (including CD8 + cells) recognize and destroy virus-infected cells and, if they recognize them, and tumor cells. Regulatory T cells (T-regs ") inhibit T-cell responses. They ensure that the immune system not to one's body "goes off". They may also prevent an immune response to tumor cells.
access * Natural killer cells (NK cells) virus-infected cells. Absence of tumor cells specific surface features, they are also attacked by NK cells.
* Macrophages are among the phagocytes and are important for innate immunity: they act as scavenger cells and contribute to the development of inflammation in - nothing negative at first, but a prerequisite for a successful immune response.
* Dendritic cells are specialized to foreign substances, to include the so-called antigens, and present to lymphocytes for recognition.
* The granulocytes include the neutrophils, the basophilic and eosinophilic cells. They are honed in on bacteria or parasites, and produce substances that are important in an inflammatory response for the transmission of signals in the body.
There are also the so-called complement system: These are not cells, but protein compounds that can bind to, for example, pathogens and other antigens. Selecting them not only for the cells of the immune system, but they do not already destroyed by this rare connection.
The immune system must be trained?
Part of the innate immune response: The complement system reacts relatively non-specific to microorganisms, phagocytes, the signal goes "foreign" to become active. Their quick response within minutes to hours to viruses and bacteria already in the first intrusion into the body fight off and prevent them from reproducing. This part of the immune system is constantly ready for use.
The situation is different when the typical and widely used features are missing, against which reacts the innate immune response - because of an infectious agent occurs for the first time, by changes no longer corresponds to the typical scheme, or because a cancer cell is mutated to a whole new way. Then the body has an immune response "tailor". The mechanisms will actively becoming known as acquired or adaptive immune response. Their reaction is specific and focused, unlike the innate immune response. Important components of this reaction, the B-and T-lymphocytes.
The immune system develops in the course of life. As training is any infection, any contact with exogenous substances and pathogens, but also any vaccination. In addition, the immune system is dependent on the general state of physical activity and nutrition, for example, the protein supply of the body.
Healthy children and adults must reckon with the occasional infectious diseases, such as a cold. The immune system works for most people still good and requires no special support.
Related Topics
* HIV and cancer
True immune disorders are rare, especially the severe congenital immunodeficiencies. Affected people are usually in childhood very sick and very vulnerable to infection. Among the hard-earned, thus not innate immune deficiency disease AIDS is the most common: Here are the viruses infect cells of the immune system. Even leukemia and lymphoma diseases affecting the immune system, because the immune cells themselves are the bearers of malicious changes here and still drive out to healthy immune cells.
Does the immune system in all parts of the body?
Most bacteria multiply mainly in the body fluids, such as in blood or tissue fluid. Viruses pull themselves back on the other hand, propagating into the interior of body cells. For this reason, the immune system has two different defense strategies at hand: one for the control of pathogens in body fluids and to remove infected and / or aged and damaged cells.
The so-called "humoral immune" (humor, Latin for body fluid) is effective against pathogens in body fluids. Their constituents are, for example, the antibodies and the complement system. The "cellular immunity" is based on the function of immune cells and is responsible for the removal of infected tissues and cells. It also serves the removal of cancer cells that have been recognized as such.
Antibodies: What functions do they have in the immune defense?
Antibodies - also called immunoglobulins - are Y-shaped protein molecules. You have an important function in human immune defense against pathogens. exogenous antibodies recognize and, where appropriate, modified endogenous structures as so-called antigens and attach themselves firmly to them. Connect them with a foreign antigen in contact, such as molecules and structures on the surface of bacteria, this is the start signal for the immune response.
Antibodies consist of three identical sections which together form a characteristic "Y" (see picture). The "V" region differs from antibody to antibody and fit only to a specific foreign substance. There, the foreign antigen is bound to be more specific "epitope". The culture of that part of the antigen that the antibody recognizes and to which it fits like a key to the castle. Typical epitopes are, for example, portions of protein molecules on the outer envelope of bacteria - would be the whole protein or other components of the bacterial envelope for the antibodies to tiny size. The leg of the antibody-"Y", the so-called "constant region" is not nearly so variable. It adapts to the cells of the immune system.
The simple structure of the antibodies allows the immune system to form when an "intruder" in the body quickly and effectively to new antibodies, such as a Toolkit: Only the variable region must be formed accordingly adjusted and new, the constant region remains the same.
Antibodies are produced by B cells. These white blood cells are highly specialized: Each B cell produces only one type of antibody that recognizes a very specific foreign character. The body has a variety of different B-cells, each of which produces a different antibody.
This allows almost unlimited diversity together with the modular design of the antibodies to detect virtually any foreign structure, the immune system is presented. The body has once been in contact with a foreign structure to provide B-cells, a kind of memory is for that antigen: an effect that accelerates the production of new antibodies significantly and is used for example for vaccination against infectious diseases.
Tumor antigens can trigger an immune response
In a similar way the immune system can also detect cells with altered genetic information that are in development for the cancer cell. They produce so-called tumor-specific or tumor-associated antigens (TAA or TSA). Only when a cancer cell, tumor antigens as "signals" gives off, can ever take place a regular immune response. As antigens, novel gene bodies, who are not as healthy cells produced. Most of the changes in tumor cells but not as tumor-specific, they also occur in healthy cells, only in another form or other frequency. For example, can be started up again in cancer cells from the embryonic development programs, in the "adult" cells are completely out of place. Or a feature is the multiplication of its building plan in the genetic material produces much too often. These abnormalities are sufficient for a natural antibody response is usually not likely, or this turns out to be weak. In cancer medicine, they still play an increasingly important role, both in diagnostics and in therapy.
Tumor antigens reach for many types of tumors into the blood ("antigen-shedding") or fall on with the targeted molecular biological tissue analysis. They can therefore use as a tumor marker in diagnosis.
Tumor-associated and tumor-specific antigens but also offer a starting point for targeted cancer treatment. Such a tumor antigen such as HER2 is. This antigen occurs in about 20 to 30 of 100 breast cancer patients before the tumor tissue in patients with gastric cancer can prove it. To a lesser extent, the feature will, however, also on healthy heart muscle tissue. With artificial antibodies that have been developed precisely to the HER-2 antigen way, today is a targeted immune therapy available.
What is the role of therapeutic antibodies play today in the treatment of cancer, the Cancer Information Service displayed in a separate text, more in "Monoclonal Antibodies: important in diagnosis and therapy."
Cellular Defense: How does the immune system defective cells?
Viruses and some bacteria remain within the interior of the infected cells from them. The immune system can not reach directly. In this case, it is necessary to destroy all the infected cells. The parties in this form of defense against infection processes are also involved in the body's control of tumor cells play a role.
Each cell presents on its surface certain protein molecules, as a kind of flag. Support this "flag" is the so-called "major histocompatibility complex (MHC, Major Histocompatibility Complex from English). The presented protein pieces (peptides) represent an image of dar. in the cell produced proteins
* Does a cell as it is, this can be at the MHC "flag" read.
* If a cell infected by a virus, by using the MHC molecules are also presented peptides of the virus. This triggers an immune reaction by which the entire cell is eventually degraded.
* Today, we know that almost all known tumor antigens via the MHC class I molecules are presented on the cell surface.
Apoptosis, the programmed cell death
The immune system is involved in other regulatory mechanisms that normally protect the body against cancer. A major task of this control is closely associated with natural aging processes. When a cell of age or so damaged that it could become a cancer cell, it must die. Usually they are even self-initiated the resolution and to reduce by immune cells. The body has to a fixed course: This "programmed cell death" is called "apoptosis" called (from the Greek apoptosis, the falling of autumn leaves). Today we know that apoptosis is controlled by very complex rules and controlled way.
One of the first parties were able to identify "signal generator", the cancer researcher, is the protein p53, whose "instruction" in the TP53 gene is located. This is a so-called tumor suppressor gene. If the genetic information of a cell is impaired, accumulated in their nucleus, this protein "p53". This protein stops the further enrichment of cell division and prevents cells with defective genes accumulate in the body. If the damage the genetic material to large to be repaired, p53 leads to cell death and for the necessary steps. The cell will escape after a specified program itself.
This in turn causes the immune system into action: The resulting residues are removed by scavenger cells of the immune system macrophages. Today it is known that apoptosis can be triggered by other means, but also to go in that cancer cells lost the ability to apoptosis can.
Failure of the natural protection mechanisms
Although cancer cells to the immune system that is not "invisible" and damage the body by various mechanisms normally seen, the formation of tumors can be removed from the control of the immune system completely. The immune research has contributed in recent years to understand these processes better and better.
Immune system and cancer: complex interplay
Cancer cells are genetically unstable - once acquired changes do not persist, new ones come. This can cause that not only remains in apoptosis, the programmed cell death, but all is lost for an immune response signals required by and by. Experts distinguish between three phases:
* In the "elimination phase" the immune system recognizes potential tumor cells and destroys them. Triggers are striking changes in cancer cells that are recognized as tumor antigens by the immune system.
* This is followed by an "equilibrium" phase of. It occurs when the elimination of tumor cells is not complete because in some tumor cells are conspicuous features have already been lost. These cells continue to change itself. This process is referred to as "immune-editing", as it encourages a kind of selection process in tumor cells with properties that make them invisible to the immune system.
* The "escape phase" occurs when the majority of further dividing tumor cells sufficient changes have accumulated to the attention of the immune system to avoid altogether. The tumor can now grow without hindrance.
Cancer cells escape the immune system (immune escape), so this is not a deliberate strategy of tumor cell origin. It is rather the result of more or less random changes in tumor cells by the immune system recognizes them not as damaged.
Immune-editing: Why cancer cells escape the immune system?
Tumors can evade immune surveillance in different ways, here are some examples:
* Tumors may not show typical tumor antigens. The immune system treats the tumor cells, such as healthy tissue.
* Wandering cancer cells, such as from the breast or the prostate can be downright "disguise" and looking like white blood cells or bone cells. The immune system does not respond, and come to the settlement and thus to metastases in the bone.
* Tumor cells are absent more, reinforcing signals that are important for the immune response - it is all over.
* Tumor cells can mobilize regulatory T cells (T-regs "). These are normally responsible for suppressing unwanted immune responses. If they are activated by tumor cells, they suppress the immune response against cancer also.
* Tumor cells can establish a physical barrier and thus protect against controlling lymphocytes. These tumors grow in the form of nodules, which are surrounded by fibrous sheaths. Do this only exceeded a certain size, a check by the immune system enough even with the destruction of the physical barrier is no longer sufficient to prevent them from growing.
Most of spontaneously occurring tumors do not seem (more) under the control of the immune system to stand. Cancer in most patients still no result of an immune defect. This shows, for example, that people with a lack of T-cells do not often get cancer than people with normal immune systems.
An exception is cancer that are caused by viruses, people who are suffering from certain forms of immunodeficiency, such as AIDS, have actually also an increased risk of these cancers.
Development of treatment methods:
What approaches pursued immunology?
For more than a hundred years an attempt is made to treat cancer by immunological methods - sometimes with astonishing results, which are not repeatable or not can be transferred from the laboratory into practice. Experiments showed that it may very well be immune reactions to tumors. However, they are often not strong enough to act as sole therapy. A major advance was to combine methods such as surgery, radiotherapy and chemotherapy with immunotherapy, but instead to rely on an immune treatment.
Immunological treatments, however, have long since not all tumor types a priority. And even in cancers for which there are appropriate therapeutic approaches, these are usually not for all patients in each disease stage or question.
* The development of monoclonal antibodies was hoping to be able to detect with the help of the selective destruction of tumors and. These treatments are therefore among the so-called targeted cancer therapies (targeted therapies), not a few have now been approved for the treatment. Such antibodies are now, however, usually not used directly against the cancer cells so that the immune system can be activated to destroy them. Most approved drugs that block cancer rather typical operations in the metabolism and prevent tumor cells from growing in this way.
* Under "Vaccinating against cancer" Doctors today understand not only the protection against infection with carcinogenic viruses. With vaccines, leading to the activation of immune cells targeting cancer cells, initial successes have been achieved in studies. The standard methods used in cancer therapy, they are not enough.
* A bit taken back the cancer researchers have the hopes they had placed on medication as cytokines, the messengers of the immune system: Interferons and interleukins are not a panacea, but contribute only a few tumor types, and even then not in all patients.
* In the broadest sense includes the transplantation of bone marrow or blood stem cells for the immunotherapy: Was it used to be used to offset the adverse effect of high dose chemotherapy or radiotherapy, it is known today that can fight directly from a foreign donor transplanted immune cells remaining cancer cells.
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