Immune system
From Freepedia
The immune system is the system of specialised cells and organs that protect an organism from outside biological influences. In a broad sense, almost every organ has a protective function (e.g., the skin). When the immune system is functioning properly, it protects the body against bacteria and viral infections, destroying cancer cells and foreign substances. If the immune system weakens, its ability to defend the body also weakens, allowing pathogens, including viruses that cause common colds and flu, to grow and flourish in the body. The immune system also performs surveillance of tumor cells, and immune suppression has been reported to increase the risk of certain types of cancer.
The immune system is often divided into two sections:
- innate immunity: encompasses unchanging mechanisms that are continuously in force to ward off noxious influences;
- adaptive immunity: responds to new influences by mounting an immune response.
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Self and non-self
The immune system defends the body by:
- recognizing agents that represent 'self' and those that represent 'non-self'; and
- launching attacks against harmful members of the latter group.
Distinguishing between self and non-self, and between harmful non-self and harmless non-self, is a difficult problem, and a variety of mammal disorders (immunodeficiency and autoimmunity) arise from the failures of their discriminatory systems.
Some self/non-self discrimination is effected by hard-wired mechanisms that recognize features displayed 'only' by pathogens. The mannan-binding lectin pathway of the complement system, for instance, recognizes mannose sugars that appear only in the polysaccharide coats of various species of bacteria.
The most versatile mechanisms of discrimination, however, are not hard-wired; rather, they involve the immune system 'learning' to recognize non-self. For instance, the plasma membrane of every 'nucleated' cell contains molecules of a large glycoprotein, called the major histocompatibility complex (MHC). These proteins have configurations and amino acid sequences that are unique to every individual. Cytotoxic T cells (T cells that directly destroy cells) contain surface-mounted receptors that are used to determine if a given cell is virally-infected by reading the peptides displayed on its MHC molecules. During their development, T cells are selected for self-reactivity. If a given cell contains receptors that bind strongly to an existing molecule in the body, it is destroyed by forced apoptosis, leaving behind T cells that can be safely released into the body.
Structure
Most multicellular organisms possess an "innate immune", generally comprising a set of genetically-encoded responses to pathogens, that does not change during the lifetime of the organism. Adaptive immunity, in which the response to pathogens changes during the lifetime of an individual, seems to have appeared somewhat abruptly in evolutionary time, with the appearance of chondrichthyes (cartilaginous or jawed fish).
Organisms that possess an adaptive immunity also possess an innate immunity, and with many of the mechanisms between the systems being common, it is not always possible to draw a hard and fast boundary between the individual components involved in each, despite the clear difference in operation. Higher vertebrates and all mammals have both an innate and an adaptive immune system.
Innate immune system
The adaptive immune system may take days or weeks, after an initial infection, to have an effect. However, most organisms are under constant assault from pathogens, which must be kept in check by the faster-acting innate immune system. Innate immunity fights pathogens using defenses that are quickly mobilized and triggered by receptors that recognize a wide spectrum of pathogens. Plants and many lower animals do not possess an adaptive immune system, and rely instead on their innate immunity.
The study of the innate immune system has recently flourished. Earlier studies of innate immunity utilized model organisms that lack adaptive immunity, such as the plant Arabidopsis thaliana, the fly Drosophila melanogaster, and the worm Caenorhabditis elegans. Recent advances have been made in the field of innate immunology with the discovery of the toll-like receptors, which are the receptors in mammal cells that are responsible for a large proportion of the innate immune recognition of pathogens. There is strong evidence that these toll-like receptors are responsible for sensing the "pathogen-associated molecular patterns" and/or providing the "danger signal", as speculated by Charles Janeway and Matzinger, respectively.
First-line defense: Physical barrier
The first-line defense includes barriers to infection, such as skin and mucus coating of the gut and airways, physically preventing the interaction between the host and the pathogen. Pathogens, which penetrate these barriers, encounter constitutively-expressed anti-microbial molecules (eg. lysozyme) that restrict the infection.
Second-line defense: Phagocytic cells
The second-line defense includes phagocytic cells (macrophages and neutrophil granulocytes) that can engulf (phagocytose) foreign substances. Macrophages are thought to mature continuously from circulating monocytes.
Phagocytosis involves chemotaxis, where phagocytic cells are attracted to microorganisms by means of chemotactic chemicals such as microbial products, complement, damaged cells and white blood cell fragments. Chemotaxis is followed by adhesion, where the phagocyte sticks to the microorganism. Adhesion is enhanced by opsonization, where proteins like opsonins are coated on the surface of the bacterium. This is followed by ingestion, in which the phagocyte extends projections, forming pseudopods that engulf the foreign organism. Finally, the bacterium is digested by the enzymes in the lysosome, involving reactive oxygen species and proteases.
Anti-microbial proteins
In addition, anti-microbial proteins may be activated if a pathogen passes through the barrier offered by skin. There are several classes of antimicrobial proteins, such as acute phase proteins (C-reactive protein, for example, enhances phagocytosis and activates complement when it binds itself to the C-protein of S. pneumoniae ), lysozyme, and the complement system.
The complement system is a very complex group of serum proteins which is activated in a cascade fashion. Three different pathways are involved in complement activation:
- classical pathway: recognizes antigen-antibody complexes;
- alternative pathway: spontaneously activates on contact with pathogenic cell surfaces; and
- mannose-binding lectin pathway: recognizes mannose sugars, which tend to appear only on pathogenic cell surfaces.
A cascade of protein activity follows complement activation; this cascade can result in a variety of effects, including opsonization of the pathogen, destruction of the pathogen by the formation and activation of the membrane attack complex, and inflammation.
Adaptive immune system
The adaptive immune system, also called the "acquired immune system", ensures that most mammals that survive an initial infection by a pathogen are generally immune to further illness, caused by that same pathogen. The adaptive immune system is based on dedicated immune cells termed leukocytes (white blood cells) that are produced by stem cells in the bone marrow, and mature in the thymus and/or lymph nodes. In many species, including mammals, the adaptive immune system can be divided into two major sections:
- Humoral immune system: It acts against bacteria and viruses in the body liquids (eg. blood) by means of proteins, called immunoglobulins (also known as antibodies), which are produced by B cells.
- Cellular immune system: It destroys virus-infected cells (among other duties) with T cells (also called "T lymphocytes"; "T" means they develop in the thymus). There are two major types of T cells:
- Cytotoxic T cells (TC cells): These cells recognize infected cells by using T cell receptors to probe cell surfaces. If they recognize an infected cell, they release granzymes to trigger that cell to become apoptotic ("commit suicide"), thus killing that cell and any viruses that it is in the process of creating.
- Helper T cells (TH cells): These cells activate infected macrophages (cells that ingest dangerous material), and also produce cytokines (interleukins) that induce the proliferation of B and T cells.
In addition, there are regulatory T cells (Treg cells) which are important in regulating cell-mediated immunity.
Intersections between systems
Splitting the innate and adaptive immunity has served to simplify discussions of immunology. However, the systems are quite intertwined in a number of important respects.
One of the most important examples are the mechanisms of 'antigen presentation'. After they leave the thymus, T cells require activation to proliferate and differentiate into cytotoxic ("killer") T cells (CTLs). Activation is provided by antigen-presenting cells (APCs), a major category of which are the dendritic cells. These cells are part of the innate immune system.
Activation occurs when a dendritic cell simultaneously binds itself to a T "helper" cell's antigen receptor and to its CD28 receptor, which provides the "second signal" needed for DC activation. This signal is a means by which the dendritic cell conveys that the antigen is indeed dangerous, and that the next encountered T "killer" cells need to be activated. This mechanism is based on antigen-danger evaluation by the T cells that belong to the adaptive immune system. But the dendritic cells are often directly activated by engaging their toll-like receptors, getting their "second signal" directly from the antigen. In this way, they actually recognize in "first person" the danger, and direct the T killer attack. In this respect, the innate immune system therefore plays a critical role in the activation of the adaptive immune system.
Adjuvants, or chemicals that stimulate an immune response, provide artificially this "second signal" in procedures when an antigen, that would not normally raise an immune response, is artificially introduced into a host. With the adjuvant, the response is much more robust. Historically, a commonly-used formula is Freund's Complete Adjuvant, an emulsion of oil and mycobacterium. It was later discovered that toll-like receptors, expressed on innate immune cells, are critical in the activation of adaptive immunity.
Disorders of the human immune system
The most important function of the human immune system occurs at the cellular level of the blood and tissues. The lymphatic and blood circulation systems are highways for specialized white blood cells to travel round the body.White blood cells include B cells, T cells, natural killer cells, and macrophages. Each has a different responsibility, but all function together with the primary objective of recognizing, attacking and destroying bacteria, viruses, cancer cells, and all substances seen as foreign. Without this coordinated effort, a person would not be able to survive more than a few days, before succumbing to overwhelming infection.
Infections set off an alarm that alerts the immune system to bring out its defensive weapons. Natural killer cells and macrophages rush to the scene to gobble up and digest infected cells. If the first line of defense fails to control the threat, antibodies, produced by the B cells, upon the order of T helper cells, are custom-designed to hone in on the invader.
Many disorders of the human immune system fall into two broad categories that are characterized by:
- Attenuated immune response: There are 'congenital' (inborn) and 'acquired' forms of immunodeficiency, characterized by an attenuated response. Chronic granulomatous disease, in which phagocytes have trouble destroying pathogens, is an example of the former, while AIDS ("Acquired Immune Deficiency Syndrome"), an infectious disease caused by the HIV virus that destroys CD4+ T cells, is an example of the latter. Immunosuppressive medication intentionally induces an immunodeficiency in order to prevent rejection of transplanted organs.
- Overzealous immune response: On the other end of the scale, an overactive immune system figures in a number of other disorders, particularly autoimmune disorders such as lupus erythematosus, type I diabetes (sometimes called "juvenile onset diabetes"), multiple sclerosis, psoriasis, and rheumatoid arthritis. In these, the immune system fails to properly distinguish between self and non-self, and attacks a part of the patient's own body. Other examples of overzealous immune responses in disease include hypersensitivities, such as allergies and asthma.
Many factors can also contribute to the general weakening of the immune system:
- Poor eating habits, and alcohol abuse;
- Drug use (particularly the use of anti-cancer drugs, corticosteroids, and antibiotics);
- Radiation;
- Exposure to environmental toxins, chemical, cigarette smoke, polluted air; and
- Stress (research show that psychological stress can greatly increase your susceptibility to colds, and other viral diseases).
The body's immunity also begins to wear down as a person gets older.
Pharmacology
Despite high hopes, there are no medications that directly increases the activity of the immune system. Various forms of medication that activate the immune system may indeed cause autoimmune disorders.
Suppression of the immune system is often used to control autoimmune disorders or inflammation when this causes excessive tissue damage, and to prevent transplant rejection after an organ transplant. Commonly used immunosuppressants include glucocorticoids, azathioprine, methotrexate, ciclosporin, cyclophosphamide and mercaptopurine. In organ transplants, ciclosporin, tacrolimus, mycophenolate mofetil and various others are used to prevent organ rejection through selective T cell inhibition.
See also
- antigen/antigenic determinant/epitope/hapten/memory cell
- autoimmune disorders
- CD4 receptor/CD8 receptor/perforin/apoptosis/clonal selection
- immunosuppression
- immunosuppressive drug
- immunotherapy
- lymphatic system/lymphocyte
- macrophage
- major histocompatibility complex/class I MHC/class II MHC
- monoclonal antibody/polyclonal antibody
Further reading
- A standard textbook on the immune system is Immunobiology, by Charles Janeway, et al. The paperback of the sixth edition is ISBN 0815341016. NCBI makes the 5th edition available electronically at [1].
| Immune system |
| Humoral immune system - Cellular immune system - Lymphatic system |
| White blood cells - B cells - Antibodies - Antigen (MHC) |
| Lymphocytes: T cells (Cytotoxic & Helper) - B cells (Plasma cells & Memory B cells) |
